The application of NMR-based metabonomics in neurological disorders

Elaine Holmes; Tsz M Tsang; Sarah J Tabrizi

doi:10.1016/j.nurx.2006.05.004

. 2012 Sep 5;3(3):358–372. doi: 10.1016/j.nurx.2006.05.004

The application of NMR-based metabonomics in neurological disorders

Elaine Holmes ^1,^✉, Tsz M Tsang ¹, Sarah J Tabrizi ²

PMCID: PMC3593384 PMID: 16815219

Summary

Advances in postgenomic technologies have radically changed the information output from complex biological systems, generating vast amounts of high complexity data that can be interpreted by means of chemometric and bioinformatic methods to achieve disease diagnosis and prognosis. High-resolution nuclear magnetic resonance (NMR) spectroscopy of biofluids such as plasma, cerebrospinal fluid (CSF), and urine can generate robust, interpretable metabolic fingerprints that contain latent information relating to physiological or pathological status. This technology has been successfully applied to both preclinical and clinical studies of neurodegenerative diseases such as Huntington’s disease, muscular dystrophy, and cerebellar ataxia. An extension of this technology,¹H magicangle-spinning (HRMAS) NMR spectroscopy, can be used to generate metabolic information on small intact tissue samples, providing a metabolic link between metabolic profiling of biofluids and histology. In this review we provide a summary of high-resolution NMR studies in neurodegenerative disease and explore the potential of metabonomics in evaluating disease progression with respect to therapeutic intervention.

Key Words: Metabonomics, NMR spectroscopy, neurodegeneration, chemometric, biomarker

References

1.Griffin JL, Sang E, Evens T, Davies K, Clarke K. Metabolic profiles of dystrophin and utrophin expression in mouse models of Duchenne muscular dystrophy. FEBS Lett. 2002;530:109–116. doi: 10.1016/s0014-5793(02)03437-3. [DOI] [PubMed] [Google Scholar]
2.Clish CB, Davidov E, Oresic M, Plasterer TN, Lavine G, Londo T, et al. Integrative biological analysis of the APOE*3-leiden transgenic mouse. Omics. 2004;8:3–13. doi: 10.1089/153623104773547453. [DOI] [PubMed] [Google Scholar]
3.Hwang D, Smith JJ, Leslie DM, Weston AD, Rust AG, Ramsey S, et al. A data integration methodology for systems biology: experimental verification. Proc Natl Acad Sci USA. 2005;102:17302–17307. doi: 10.1073/pnas.0508649102. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Miller RM, Federoff HJ. Microarrays in Parkinson’s disease: a systematic approach. NeuroRx. 2006;3:318–325. doi: 10.1016/j.nurx.2006.05.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Olson NE. The microarray data analysis process: from raw to biological significance. NeuroRx. 2006;3:371–381. doi: 10.1016/j.nurx.2006.05.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Nicholson JK, Lindon JC, Holmes E. ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica. 1999;29:1181–1189. doi: 10.1080/004982599238047. [DOI] [PubMed] [Google Scholar]
7.Nicholson JK, Connelly J, Lindon JC, Holmes E. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov. 2002;1:153–161. doi: 10.1038/nrd728. [DOI] [PubMed] [Google Scholar]
8.Fiehn O. Metabolomics: the link between genotypes and phenotypes. Plant Mol Biol. 2002;48:155–171. [PubMed] [Google Scholar]
9.Yang J, Xu G, Zheng Y, Kong H, Pang T, Lv S, et al. Diagnosis of liver cancer using HPLC-based metabonomics avoiding false-positive result from hepatitis and hepatocirrhosis diseases. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;813:59–65. doi: 10.1016/j.jchromb.2004.09.032. [DOI] [PubMed] [Google Scholar]
10.Odunsi K, Wollman RM, Ambrosone CB, Hutson A, McCann SE, Tammela J, et al. Detection of epithelial ovarian cancer using 1H-NMR-based metabonomics. Int J Cancer. 2005;113:782–788. doi: 10.1002/ijc.20651. [DOI] [PubMed] [Google Scholar]
11.Griffiths JR, Stubbs M. Opportunities for studying cancer by metabolomics: preliminary observations on tumors deficient in hypoxia-inducible factor 1. Adv Enzyme Regul. 2003;43:67–76. doi: 10.1016/s0065-2571(02)00030-4. [DOI] [PubMed] [Google Scholar]
12.Yang J, Xu G, Hong Q, Liebich HM, Lutz K, Schmulling RM, et al. Discrimination of Type 2 diabetic patients from healthy controls by using metabonomics method based on their serum fatty acid profiles. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;813:53–58. doi: 10.1016/j.jchromb.2004.09.023. [DOI] [PubMed] [Google Scholar]
13.Brindle JT, Antti H, Holmes E, Tranter G, Nicholson JK, Bethell HW, et al. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nat Med. 2002;8:1439–1444. doi: 10.1038/nm1202-802. [DOI] [PubMed] [Google Scholar]
14.Sabatine MS, Liu E, Morrow DA, Heller E, McCarroll R, Wiegand R, et al. Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation. 2005;112:3868–3875. doi: 10.1161/CIRCULATIONAHA.105.569137. [DOI] [PubMed] [Google Scholar]
15.Griffin JL, Cemal CK, Pook MA. Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3. Physiol Genomics. 2004;16:334–340. doi: 10.1152/physiolgenomics.00149.2003. [DOI] [PubMed] [Google Scholar]
16.Dunckley T, Coon KD, Stephan DA. Discovery and development of biomarkers of neurological disease. Drug Discov Today. 2005;10:326–334. doi: 10.1016/S1359-6446(04)03353-7. [DOI] [PubMed] [Google Scholar]
17.Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL, et al. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry. 2004;9:684–697. doi: 10.1038/sj.mp.4001511. [DOI] [PubMed] [Google Scholar]
18.Barshop BA. Metabolomic approaches to mitochondrial disease: correlation of urine organic acids. Mitochondrion. 2004;4:521–527. doi: 10.1016/j.mito.2004.07.010. [DOI] [PubMed] [Google Scholar]
19.Coen M, O’Sullivan M, Bubb WA, Kuchel PW, Sorrell T. Proton nuclear magnetic resonance-based metabonomics for rapid diagnosis of meningitis and ventriculitis. Clin Infect Dis. 2005;41:1582–1590. doi: 10.1086/497836. [DOI] [PubMed] [Google Scholar]
20.Braun KP, Gooskens RH, Vandertop WP, Tulleken CA, van der Grond J. 1H magnetic resonance spectroscopy in human hydro-cephalus. J Magn Reson Imaging. 2003;17:291–299. doi: 10.1002/jmri.10270. [DOI] [PubMed] [Google Scholar]
21.Wang Y, Holmes E, Nicholson JK, Cloarec O, Chollet J, Tanner M, et al. Metabonomic investigations in mice infected withSchistosoma mansoni: an approach for biomarker identification. Proc Natl Acad Sci USA. 2004;101:12676–12681. doi: 10.1073/pnas.0404878101. [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Rudkin TM, Arnold DL. Proton magnetic resonance spectroscopy for the diagnosis and management of cerebral disorders. Arch Neurol. 1999;56:919–926. doi: 10.1001/archneur.56.8.919. [DOI] [PubMed] [Google Scholar]
23.Kapeller P, McLean MA, Griffin CM, Chard D, Parker GJ, Barker GJ, et al. Preliminary evidence for neuronal damage in cortical grey matter and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study. J Neurol. 2001;248:131–138. doi: 10.1007/s004150170248. [DOI] [PubMed] [Google Scholar]
24.Karrenbauer VD, Leoni V, Lim ET, Giovannoni G, Ingle GT, Sastre-Garriga J, et al. Plasma cerebrosterol and magnetic resonance imaging measures in multiple sclerosis. Clin Neurol Neurosurg. 2006;108:456–460. doi: 10.1016/j.clineuro.2005.07.010. [DOI] [PubMed] [Google Scholar]
25.Tartaglia MC, Arnold DL. The role of MRS and fMRI in multiple sclerosis. Adv Neurol. 2006;98:185–202. [PubMed] [Google Scholar]
26.Frisoni GB, Filippi M. Multiple sclerosis and Alzheimer’s disease through the looking glass of MR imaging. AJNR Am J Neuroradiol. 2005;26:2488–2491. [PMC free article] [PubMed] [Google Scholar]
27.Kleiner-Fisman G, Bergeron C, Lang AE. Presentation of Creutzfeldt—Jakob disease as acute corticobasal degeneration syndrome. Mov Disord. 2004;19:948–949. doi: 10.1002/mds.20140. [DOI] [PubMed] [Google Scholar]
28.Jenkins BG, Koroshetz WJ, Beal MF, Rosen BR. Evidence for impairment of energy metabolism in vivo in Huntington’s disease using localized 1H NMR spectroscopy. Neurology. 1993;43:2689–2695. doi: 10.1212/wnl.43.12.2689. [DOI] [PubMed] [Google Scholar]
29.Brouwer OF, Laboyrie PM, Peters AC, Vielvoye GJ. Follow-up magnetic resonance imaging in Hallervorden-Spatz disease. Clin Neurol Neurosurg. 1992;94:S57–S60. doi: 10.1016/0303-8467(92)90023-v. [DOI] [PubMed] [Google Scholar]
30.Kang PB, Hunter JV, Kaye EM. Lactic acid elevation in extra-mitochondrial childhood neurodegenerative diseases. J Child Neurol. 2001;16:657–660. doi: 10.1177/088307380101600906. [DOI] [PubMed] [Google Scholar]
31.Khiat A, Bard C, Lacroix A, Rousseau J, Boulanger Y. Brain metabolic alterations in Cushing’s syndrome as monitored by proton magnetic resonance spectroscopy. NMR Biomed. 1999;12:357–363. doi: 10.1002/(sici)1099-1492(199910)12:6<357::aid-nbm584>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
32.Khiat A, Yared Z, Bard C, Lacroix A, Boulanger Y. Long-term brain metabolic alterations in exogenous Cushing’s syndrome as monitored by proton magnetic resonance spectroscopy. Brain Res. 2001;911:134–140. doi: 10.1016/s0006-8993(01)02697-x. [DOI] [PubMed] [Google Scholar]
33.Gallelli KA, Wagner CM, Karchemskiy A, Howe M, Spielman D, Reiss A, et al. N-acetylaspartate levels in bipolar offspring with and at high-risk for bipolar disorder. Bipolar Disord. 2005;7:589–597. doi: 10.1111/j.1399-5618.2005.00266.x. [DOI] [PubMed] [Google Scholar]
34.Choi IY, Lee SP, Guilfoyle DN, Helpern JA. In vivo NMR studies of neurodegenerative diseases in transgenic and rodent models. Neurochem Res. 2003;28:987–1001. doi: 10.1023/a:1023370104289. [DOI] [PubMed] [Google Scholar]
35.Li LM, Caramanos Z, Cendes F, Andermann F, Antel SB, Dubeau F, et al. Lateralization of temporal lobe epilepsy (TLE) and discrimination of TLE from extra-TLE using pattern analysis of magnetic resonance spectroscopic and volumetric data. Epilepsia. 2000;41:832–842. doi: 10.1111/j.1528-1157.2000.tb00250.x. [DOI] [PubMed] [Google Scholar]
36.Kalra S, Arnold DL, Cashman NR. Biological markers in the diagnosis and treatment of ALS. J Neurol Sci. 1999;165:S27–S32. doi: 10.1016/s0022-510x(99)00023-4. [DOI] [PubMed] [Google Scholar]
37.Matthews PM, Pioro E, Narayanan S, De Stefano N, Fu L, Francis G, et al. Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy. Brain. 1996;119:715–722. doi: 10.1093/brain/119.3.715. [DOI] [PubMed] [Google Scholar]
38.Seppi K, Schocke MF. An update on conventional and advanced magnetic resonance imaging techniques in the differential diagnosis of neurodegenerative parkinsonism. Curr Opin Neurol. 2005;18:370–375. doi: 10.1097/01.wco.0000173141.74137.63. [DOI] [PubMed] [Google Scholar]
39.Kasparova S, Sumbalova Z, Bystricky P, Kucharska J, Liptaj T, Mlynarik V, et al. Effect of coenzyme Q10 and vitamin E on brain energy metabolism in the animal model of Huntington’s disease. Neurochem Int. 2006;48:93–99. doi: 10.1016/j.neuint.2005.09.002. [DOI] [PubMed] [Google Scholar]
40.Fernandez A, Garcia-Segura JM, Ortiz T, Montoya J, Maestu F, Gil-Gregorio P, et al. Proton magnetic resonance spectroscopy and magnetoencephalographic estimation of delta dipole density: a combination of techniques that may contribute to the diagnosis of Alzheimer’s disease. Dement Geriatr Cogn Disord. 2005;20:169–177. doi: 10.1159/000087094. [DOI] [PubMed] [Google Scholar]
41.Pfefferbaum A, Adalsteinsson E, Spielman D, Sullivan EV, Lim KO. In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer’s disease. Arch Gen Psychiatry. 1999;56:185–192. doi: 10.1001/archpsyc.56.2.185. [DOI] [PubMed] [Google Scholar]
42.Preul MC, Caramanos Z, Collins DL, Villemure JG, Leblanc R, Olivier A, et al. Accurate, noninvasive diagnosis of human brain tumors by using proton magnetic resonance spectroscopy. Nat Med. 1996;2:323–325. doi: 10.1038/nm0396-323. [DOI] [PubMed] [Google Scholar]
43.Brown FF, Campbell ID, Kuchel PW, Rabenstein DC. Human erythrocyte metabolism studies by 1H spin echo NMR. FEBS Lett. 1977;82:12–16. doi: 10.1016/0014-5793(77)80875-2. [DOI] [PubMed] [Google Scholar]
44.Ohsaka A, Yoshikawa K, Matuhasi T. Detection by proton nuclear magnetic resonance of elevated lactate concentration in serums from patients with malignant tumors. Jpn J Med Sci Biol. 1979;32:305–309. doi: 10.7883/yoken1952.32.305. [DOI] [PubMed] [Google Scholar]
45.Bales JR, Higham DP, Howe I, Nicholson JK, Sadler PJ. Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin Chem. 1984;30:426–432. [PubMed] [Google Scholar]
46.Nicholson JK, Buckingham MJ, Sadler PJ. High resolution 1H n.m.r. studies of vertebrate blood and plasma. Biochem J. 1983;211:605–615. doi: 10.1042/bj2110605. [DOI] [PMC free article] [PubMed] [Google Scholar]
47.Nicholson JK, Timbrell JA, Sadler PJ. Proton NMR spectra of urine as indicators of renal damage: mercury-induced nephrotoxicity in rats. Mol Pharmacol. 1985;27:644–651. [PubMed] [Google Scholar]
48.Cheng LL, Newell K, Mallory AE, Hyman BT, Gonzalez RG. Quantification of neurons in Alzheimer and control brains with ex vivo high resolution magic angle spinning proton magnetic resonance spectroscopy and stereology. Magn Reson Imaging. 2002;20:527–533. doi: 10.1016/s0730-725x(02)00512-x. [DOI] [PubMed] [Google Scholar]
49.Cheng LL, Chang IW, Louis DN, Gonzalez RG. Correlation of high-resolution magic angle spinning proton magnetic resonance spectroscopy with histopathology of intact human brain tumor specimens. Cancer Res. 1998;58:1825–1832. [PubMed] [Google Scholar]
50.Cheng LL, Ma MJ, Becerra L, Ptak T, Tracey I, Lackner A, et al. Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc Natl Acad Sci USA. 1997;94:6408–6413. doi: 10.1073/pnas.94.12.6408. [DOI] [PMC free article] [PubMed] [Google Scholar]
51.Barton SJ, Howe FA, Tomlins AM, Cudlip SA, Nicholson JK, Bell BA, et al. Comparison of in vivo 1H MRS of human brain tumours with 1H HR-MAS spectroscopy of intact biopsy samplesin vitro. Magma. 1999;8:121–128. doi: 10.1007/BF02590529. [DOI] [PubMed] [Google Scholar]
52.Fu R, Brey WW, Shetty K, Gor’kov P, Saha S, Long JR, et al. Ultra-wide bore 900 MHz high-resolution NMR at the National High Magnetic Field Laboratory. J Magn Reson. 2005;177:1–8. doi: 10.1016/j.jmr.2005.07.013. [DOI] [PubMed] [Google Scholar]
53.Sidelmann UG, Braumann U, Hoffmann M, Spraul M, Lindon JC, Nicholson JK, et al. Directly coupled 800 MHz HPLC-NMR spectroscopy of urine and its applications to the identification of the major phase II metabolites of tolfenamic acid. Anal Chem. 1997;69:607–612. [Google Scholar]
54.Martin GE, Hadden CE, Russell DJ, Kaluzny BD, Guido JE, Duholke WK, et al. Identification of degradants of a complex alkaloid using NMR cryoprobe technology and ACD/structure elucidator. J Heterocyclic Chem. 2002;39:1241–1250. [Google Scholar]
55.Griffin JL, Lehtimaki KK, Valonen PK, Grohn OH, Kettunen MI, Yla-Herttuala S, et al. Assignment of (1)H nuclear magnetic resonance visible polyunsaturated fatty acids in BT4C gliomas undergoing ganciclovir-thymidine kinase gene therapy-induced programmed cell death. Cancer Res. 2003;63:3195–3201. [PubMed] [Google Scholar]
56.Hinse C, Richter C, Provenzani A, Stockigt J. In vivo monitoring of alkaloid metabolism in hybrid plant cell cultures by 2D cryo-NMR without labeling. Bioorg Med Chem. 2003;11:3913–3919. doi: 10.1016/s0968-0896(03)00430-9. [DOI] [PubMed] [Google Scholar]
57.Beckwith-Hall BM, Nicholson JK, Nicholls AW, Foxall PJ, Lindon JC, Connor SC, et al. Nuclear magnetic resonance spectroscopic and principal components analysis investigations into biochemical effects of three model hepatotoxins. Chem Res Toxicol. 1998;11:260–272. doi: 10.1021/tx9700679. [DOI] [PubMed] [Google Scholar]
58.Nicholson JK, Foxall PJ, Spraul M, Fanant RD, Lindon JC. 750 MHz 1H and 1H-13C NMR spectroscopy of human blood plasma. Anal Chem. 1995;67:793–811. doi: 10.1021/ac00101a004. [DOI] [PubMed] [Google Scholar]
59.Sathasivam K, Baxendale S, Mangiarini L, Bertaux F, Hetherington C, Kanazawa I, et al. Aberrant processing of the Fugu HD (FrHD) mRNA in mouse cells and in transgenic mice. Hum Mol Genet. 1997;6:2141–2149. doi: 10.1093/hmg/6.12.2141. [DOI] [PubMed] [Google Scholar]
60.Van Zijl PCM, O’Neil Johnson M, Mori S, Hurd RE. Magic-angle-gradient double-quantum-filtered COSY. J Magn Reson. 1995;113A:265–270. [Google Scholar]
61.Shockcor JP, Unger SE, Wilson ID, Foxall PJ, Nicholson JK, Lindon JC. Combined HPLC, NMR spectroscopy, and ion-trap mass spectrometry with application to the detection and characterization of xenobiotic and endogenous metabolites in human urine. Anal Chem. 1996;68:4431–4435. doi: 10.1021/ac9606463. [DOI] [PubMed] [Google Scholar]
62.Lindon JC, Nicholson JK, Holmes E, Keun HC, Craig A, Pearce JT, et al. Summary recommendations for standardization and reporting of metabolic analyses. Nat Biotechnol. 2005;23:833–838. doi: 10.1038/nbt0705-833. [DOI] [PubMed] [Google Scholar]
63.Garrod S, Humpher E, Connor SC, Connelly JC, Spraul M, Nicholson JK, et al. High-resolution (1)H NMR and magic angle spinning NMR spectroscopic investigation of the biochemical effects of 2-bromoethanamine in intact renal and hepatic tissue. Magn Reson Med. 2001;45:781–790. doi: 10.1002/mrm.1106. [DOI] [PubMed] [Google Scholar]
64.Moka D, Vorreuther R, Schicha H, Spraul M, Humpfer E, Lipinski M, et al. Biochemical classification of kidney carcinoma biopsy samples using magic-angle-spinning 1H nuclear magnetic resonance spectroscopy. J Pharm Biomed Anal. 1998;17:125–132. doi: 10.1016/s0731-7085(97)00176-3. [DOI] [PubMed] [Google Scholar]
65.Tomlins AM, Foxall PJ, Lynch MJ, Parkinson J, Everett JR, Nicholson JK. High resolution 1H NMR spectroscopic studies on dynamic biochemical processes in incubated human seminal fluid samples. Biochim Biophys Acta. 1998;1379:367–380. doi: 10.1016/s0304-4165(97)00116-5. [DOI] [PubMed] [Google Scholar]
66.Tate AR, Foxall PJ, Holmes E, Moka D, Spraul M, Nicholson JK, et al. Distinction between normal and renal cell carcinoma kidney cortical biopsy samples using pattern recognition of (1)H magic angle spinning (MAS) NMR spectra. NMR Biomed. 2000;13:64–71. doi: 10.1002/(sici)1099-1492(200004)13:2<64::aid-nbm612>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
67.Eriksson L, Antti H, Gottfries J, Holmes E, Johansson E, Lindgren F, et al. Using chemometrics for navigating in the large data sets of genomics, proteomics, and metabonomics (gpm) Anal Bioanal Chem. 2004;380:419–429. doi: 10.1007/s00216-004-2783-y. [DOI] [PubMed] [Google Scholar]
68.Trygg J, Wold S. O2-PLS, a two-block (X-Y) latent variable regression (LVR) method with an integral OSC filter. J Chemometrics. 2003;17:53–64. [Google Scholar]
69.Turmaine M, Raza A, Mahal A, Mangiarini L, Bates GP, Davies SW. Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington’s disease. Proc Natl Acad Sci USA. 2000;97:8093–8097. doi: 10.1073/pnas.110078997. [DOI] [PMC free article] [PubMed] [Google Scholar]
70.Huang Y, Lisboa PJ, El-Deredy W. Tumour grading from magnetic resonance spectroscopy: a comparison of feature extraction with variable selection. Stat Med. 2003;22(1):147–164. doi: 10.1002/sim.1321. [DOI] [PubMed] [Google Scholar]
71.Cloarec O, Dumas ME, Trygg J, Craig A, Barton RH, Lindon JC, et al. Evaluation of the orthogonal projection on latent structure model limitations caused by chemical shift variability and improved visualization of biomarker changes in 1H NMR spectroscopic metabonomic studies. Anal Chem. 2005;77:517–526. doi: 10.1021/ac048803i. [DOI] [PubMed] [Google Scholar]
72.Ma’ayan A, Gardiner K, Iyengar R. The cognitive phenotype of Down syndrome: insights from intracellular network analysis. NeuroRx. 2006;3:394–403. doi: 10.1016/j.nurx.2006.05.036. [DOI] [PMC free article] [PubMed] [Google Scholar]
73.Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed. 2000;13:129–153. doi: 10.1002/1099-1492(200005)13:3<129::aid-nbm619>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
74.Pfeuffer J, Tkac I, Provencher SW, Gruetter R. Toward an in vivo neurochemical profile: quantification of 18 metabolites in shortecho-time (1)H NMR spectra of the rat brain. J Magn Reson. 1999;141:104–120. doi: 10.1006/jmre.1999.1895. [DOI] [PubMed] [Google Scholar]
75.Tsang TM, Griffin JL, Haselden J, Fish C, Holmes E. Metabolic characterization of distinct neuroanatomical regions in rats by magic angle spinning 1H nuclear magnetic resonance spectroscopy. Magn Reson Med. 2005;53:1018–1024. doi: 10.1002/mrm.20447. [DOI] [PubMed] [Google Scholar]
76.Tsang TM, Woodman B, McLoughlin GA, Griffin JL, Tabrizi SJ, Bates GP, et al. Metabolic characterization of the R6/2 transgenic mouse model of Huntington’s disease by high-resolution MAS 1H NMR spectroscopy. J Proteome Res. 2006;5:483–492. doi: 10.1021/pr050244o. [DOI] [PubMed] [Google Scholar]
77.Griffin JL, Bollard M, Nicholson JK, Bhakoo K. Spectral profiles of cultured neuronal and glial cells derived from HRMAS (1)H NMR spectroscopy. NMR Biomed. 2002;15:375–384. doi: 10.1002/nbm.792. [DOI] [PubMed] [Google Scholar]
78.Urenjak J, Williams SR, Gadian DG, Noble M. Specific expression of N-acetylaspartate in neurons, oligodendrocyte-type-2 astrocyte progenitors, and immature oligodendrocytesin vitro. J Neurochem. 1992;59:55–61. doi: 10.1111/j.1471-4159.1992.tb08875.x. [DOI] [PubMed] [Google Scholar]
79.Hoang TQ, Bluml S, Dubowitz DJ, Moats R, Kopyov O, Jacques D, et al. Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington’s and Parkinson’s diseases. Neurology. 1998;50:1033–1040. doi: 10.1212/wnl.50.4.1033. [DOI] [PubMed] [Google Scholar]
80.Jenkins BG, Brouillet E, Chen YC, Storey E, Schulz JB, Kirschner P, et al. Non-invasive neurochemical analysis of focal excitotoxic lesions in models of neurodegenerative illness using spectroscopic imaging. J Cereb Blood Flow Metab. 1996;16:450–461. doi: 10.1097/00004647-199605000-00011. [DOI] [PubMed] [Google Scholar]
81.Jenkins BG, Rosas HD, Chen YC, Makabe T, Myers R, Mac-Donald M, et al. 1H NMR spectroscopy studies of Huntington’s disease: correlations with CAG repeat numbers. Neurology. 1998;50:1357–1365. doi: 10.1212/wnl.50.5.1357. [DOI] [PubMed] [Google Scholar]
82.Horska A, Naidu S, Herskovits EH, Wang PY, Kaufmann WE, Barker PB. Quantitative 1H MR spectroscopic imaging in early Rett syndrome. Neurology. 2000;54:715–722. doi: 10.1212/wnl.54.3.715. [DOI] [PubMed] [Google Scholar]
83.Lucetti C, Del Dotto P, Gambaccini G, Bernardini S, Bianchi MC, Tosetti M, et al. Proton magnetic resonance spectroscopy (1H-MRS) of motor cortex and basal ganglia in de novo Parkinson’s disease patients. Neurol Sci. 2001;22:69–70. doi: 10.1007/s100720170051. [DOI] [PubMed] [Google Scholar]
84.Tourbah A, Stievenart JL, Gout O, Fontaine B, Liblau R, Lubetzki C, et al. Localized proton magnetic resonance spectroscopy in relapsing remitting versus secondary progressive multiple sclerosis. Neurology. 1999;53:1091–1097. doi: 10.1212/wnl.53.5.1091. [DOI] [PubMed] [Google Scholar]
85.Pears MR, Cooper JD, Mitchison HM, Mortishire-Smith RJ, Pearce DA, Griffin JL. High resolution 1H NMR-based metabolomics indicates a neurotransmitter cycling deficit in cerebral tissue from a mouse model of Batten disease. J Biol Chem. 2005;280:42508–42514. doi: 10.1074/jbc.M507380200. [DOI] [PubMed] [Google Scholar]
86.Viant MR, Lyeth BG, Miller MG, Berman RF. An NMR metabolomic investigation of early metabolic disturbances following traumatic brain injury in a mammalian model. NMR Biomed. 2005;18:507–516. doi: 10.1002/nbm.980. [DOI] [PubMed] [Google Scholar]
87.Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R, et al. Parkinson’s disease in twins: an etiologic study. Jama. 1999;281:341–346. doi: 10.1001/jama.281.4.341. [DOI] [PubMed] [Google Scholar]
88.Weeks RA, Piccini P, Harding AE, Brooks DJ. Striatal D1 and D2 dopamine receptor loss in asymptomatic mutation carriers of Huntington’s disease. Ann Neurol. 1996;40:49–54. doi: 10.1002/ana.410400110. [DOI] [PubMed] [Google Scholar]
89.Sveinbjomsdottir S, Hicks AA, Jonsson T, Petursson H, Gugmundsson G, Frigge ML, et al. Familial aggregation of Parkinson’s disease in Iceland. N Engl J Med. 2000;343:1765–1770. doi: 10.1056/NEJM200012143432404. [DOI] [PubMed] [Google Scholar]
90.Bender A, Auer DP, Merl T, Reilmann R, Saemann P, Yassouridis A, et al. Creatine supplementation lowers brain glutamate levels in Huntington’s disease. J Neurol. 2005;252:36–41. doi: 10.1007/s00415-005-0595-4. [DOI] [PubMed] [Google Scholar]
91.Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–608. doi: 10.1038/33416. [DOI] [PubMed] [Google Scholar]
92.Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, et al. Ala30Pro mutation in the gene encoding α-synuclein in Parkinson’s disease. Nat Genet. 1998;18:106–108. doi: 10.1038/ng0298-106. [DOI] [PubMed] [Google Scholar]
93.Brouillet E, Hantraye P, Ferrante RJ, Dolan R, Leroy-Willig A, Kowall NW, et al. Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc Natl Acad Sci USA. 1995;92:7105–7109. doi: 10.1073/pnas.92.15.7105. [DOI] [PMC free article] [PubMed] [Google Scholar]
94.Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276:2045–2047. doi: 10.1126/science.276.5321.2045. [DOI] [PubMed] [Google Scholar]
95.Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2003;299:256–259. doi: 10.1126/science.1077209. [DOI] [PubMed] [Google Scholar]
96.Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44:595–600. doi: 10.1016/j.neuron.2004.10.023. [DOI] [PubMed] [Google Scholar]
97.Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science. 2004;304:1158–1160. doi: 10.1126/science.1096284. [DOI] [PubMed] [Google Scholar]
98.Klawans HL, Stein RW, Tanner CM, Goetz CG. A pure parkinsonian syndrome following acute carbon monoxide intoxication. Arch Neurol. 1982;39:302–304. doi: 10.1001/archneur.1982.00510170044012. [DOI] [PubMed] [Google Scholar]
99.Huang CC, Lu CS, Chu NS, Hochberg F, Lilienfeld D, Olanow W, et al. Progression after chronic manganese exposure. Neurology. 1993;43:1479–1483. doi: 10.1212/wnl.43.8.1479. [DOI] [PubMed] [Google Scholar]
100.Helmuth L. Neuroscience. Pesticide causes Parkinson’s in rats. Science. 2000;290:1068–1068. doi: 10.1126/science.290.5494.1068a. [DOI] [PubMed] [Google Scholar]
101.Langsten JW, Fomo LS, Rebert CS, Irwin I. Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey. Brain Res. 1984;292:390–394. doi: 10.1016/0006-8993(84)90777-7. [DOI] [PubMed] [Google Scholar]
102.Carlsson A, Lindqvist M, Magnusson T. 3,4-Dihydroxypheny-lalanine and 5-hydroxytryptophan as reserpine antagonists. Nature. 1957;180:1200–1200. doi: 10.1038/1801200a0. [DOI] [PubMed] [Google Scholar]
103.Ungerstedt U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol. 1968;5:107–110. doi: 10.1016/0014-2999(68)90164-7. [DOI] [PubMed] [Google Scholar]
104.Hastings TG, Lewis DA, Zigmond MJ. Role of oxidation in the neurotoxic effects of intrastriatal dopamine injections. Proc Natl Acad Sci USA. 1996;93:1956–1961. doi: 10.1073/pnas.93.5.1956. [DOI] [PMC free article] [PubMed] [Google Scholar]
105.Bloem BR, Irwin I, Buruma OJ, Haan J, Roos RA, Tetrud JW, et al. The MPTP model: versatile contributions to the treatment of idiopathic Parkinson’s disease. J Neurol Sci. 1990;97:273–293. doi: 10.1016/0022-510x(90)90225-c. [DOI] [PubMed] [Google Scholar]
106.Chen YC, Galpern WR, Brownell AL, Matthews RT, Bogdanov M, Isacson O, et al. Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: correlation with PET, micro-dialysis, and behavioral data. Magn Reson Med. 1997;38:389–398. doi: 10.1002/mrm.1910380306. [DOI] [PubMed] [Google Scholar]
107.Smith DA, Clarke LP, Fiedler JA, Murtagh FR, Bonaroti EA, Sengstock GJ, et al. Use of a clinical MR scanner for imaging the rat brain. Brain Res Bull. 1993;31:115–120. doi: 10.1016/0361-9230(93)90017-6. [DOI] [PubMed] [Google Scholar]
108.Boska MD, Lewis TB, Destache CJ, Benner EJ, Nelson JA, Uberti M, et al. Quantitative 1H magnetic resonance spectroscopic imaging determines therapeutic immunization efficacy in an animal model of Parkinson’s disease. J Neurosci. 2005;25:1691–1700. doi: 10.1523/JNEUROSCI.4364-04.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
109.Brownell AL, Jenkins BG, Elmaleh DR, Deacon TW, Spealman RD, Isacson O. Combined PET/MRS brain studies show dynamic and long-term physiological changes in a primate model of Parkinson’s disease. Nat Med. 1998;4:1308–1312. doi: 10.1038/3300. [DOI] [PubMed] [Google Scholar]
110.Podell M, Hadjiconstantinou M, Smith MA, Neff NH. Proton magnetic resonance imaging and spectroscopy identify metabolic changes in the striatum in the MPTP feline model of parkinsonism. Exp Neurol. 2003;179:159–166. doi: 10.1016/s0014-4886(02)00015-8. [DOI] [PubMed] [Google Scholar]
111.Sperk G. Kainic acid seizures in the rat. Prog Neurobiol. 1994;42:1–32. doi: 10.1016/0301-0082(94)90019-1. [DOI] [PubMed] [Google Scholar]
112.Brouillet E, Conde F, Beal MF, Hantraye P. Replicating Huntington’s disease phenotype in experimental animals. Prog Neurobiol. 1999;59:427–468. doi: 10.1016/s0301-0082(99)00005-2. [DOI] [PubMed] [Google Scholar]
113.Dautry C, Conde F, Brouillet E, Mittoux V, Beal MF, Bloch G, et al. Serial 1H-NMR spectroscopy study of metabolic impairment in primates chronically treated with the succinate dehydrogenase inhibitor 3-nitropropionic acid. Neurobiol Dis. 1999;6:259–268. doi: 10.1006/nbdi.1999.0244. [DOI] [PubMed] [Google Scholar]
114.Palfi S, Conde F, Riche D, Brouillet E, Dautry C, Mittoux V, et al. Fetal striatal allografts reverse cognitive deficits in a primate model of Huntington’s disease. Nat Med. 1998;4:963–966. doi: 10.1038/nm0898-963. [DOI] [PubMed] [Google Scholar]
115.Mittoux V, Joseph JM, Conde F, Palfi S, Dautry C, Poyot T, et al. Restoration of cognitive and motor functions by ciliary neurotrophic factor in a primate model of Huntington’s disease. Hum Gene Ther. 2000;11:1177–1187. doi: 10.1089/10430340050015220. [DOI] [PubMed] [Google Scholar]
116.Garrod S, Bollard ME, Nicholls AW, Connor SC, Connelly J, Nicholson JK, et al. Integrated metabonomic analysis of the multiorgan effects of hydrazine toxicity in the rat. Chem Res Toxicol. 2005;18:115–122. doi: 10.1021/tx0498915. [DOI] [PubMed] [Google Scholar]
117.Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, et al. Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science. 2000;287:1265–1269. doi: 10.1126/science.287.5456.1265. [DOI] [PubMed] [Google Scholar]
118.Richfield EK, O’Brien CF, Eskin T, Shoulson I. Heterogeneous dopamine receptor changes in early and late Huntington’s disease. Neurosci Lett. 1991;132:121–126. doi: 10.1016/0304-3940(91)90448-3. [DOI] [PubMed] [Google Scholar]
119.Holowenko D, Peeling J, Sutherland G. 1H NMR properties of N-acetylaspartylglutamate in extracts of nervous tissue of the rat. NMR Biomed. 1992;5:43–47. doi: 10.1002/nbm.1940050108. [DOI] [PubMed] [Google Scholar]
120.van Dellen A, Welch J, Dixon RM, Cordery P, York D, Styles P, et al. N-acetylaspartate and DARPP-32 levels decrease in the corpus striatum of Huntington’s disease mice. NeuroReport. 2000;11:3751–3757. doi: 10.1097/00001756-200011270-00032. [DOI] [PubMed] [Google Scholar]
121.Jenkins BG, Klivenyi P, Kustermann E, Andreassen OA, Ferrante RJ, Rosen BR, et al. Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington’s disease mice. J Neurochem. 2000;74:2108–2119. doi: 10.1046/j.1471-4159.2000.0742108.x. [DOI] [PubMed] [Google Scholar]
122.Underwood BR, Broadhurst D, Dunn WB, Ellis DI, Michell AW, Vacher C, et al. Huntington’s disease patients and transgenic mice have similar pro-catabolic serum metabolite profiles. Brain. 2006;129:877–886. doi: 10.1093/brain/awl027. [DOI] [PubMed] [Google Scholar]
123.Henley SM, Bates GP, Tabrizi SJ. Biomarkers for neurodegenerative diseases. Curr Opin Neurol. 2005;18:698–705. doi: 10.1097/01.wco.0000186842.51129.cb. [DOI] [PubMed] [Google Scholar]
124.Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, et al. Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004;256:240–246. doi: 10.1111/j.1365-2796.2004.01380.x. [DOI] [PubMed] [Google Scholar]
125.DeCarli C. Mild cognitive impairment: prevalence, prognosis, aetiology, and treatment. Lancet Neurol. 2003;2:15–21. doi: 10.1016/s1474-4422(03)00262-x. [DOI] [PubMed] [Google Scholar]
126.Metastasio A, Rinaldi P, Tarducci R, Mariani E, Feliziani FT, Cherubim A, et al. Conversion of MCI to dementia: role of proton magnetic resonance spectroscopy. Neurobiol Aging. 2006;27:926–932. doi: 10.1016/j.neurobiolaging.2005.05.002. [DOI] [PubMed] [Google Scholar]
127.Frederick BD, Lyoo IK, Satlin A, Ahn KH, Kim MJ, Yurgelun-Todd DA, et al. In vivo proton magnetic resonance spectroscopy of the temporal lobe in Alzheimer’s disease. Prog Neuropsycho-pharmacol Biol Psychiatry. 2004;28:1313–1322. doi: 10.1016/j.pnpbp.2004.08.013. [DOI] [PubMed] [Google Scholar]
128.Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. α-synuclein in Lewy bodies. Nature. 1997;388:839–840. doi: 10.1038/42166. [DOI] [PubMed] [Google Scholar]
129.Schlossmacher MG, Frosch MP, Gai WP, Medina M, Sharma N, Fomo L, et al. Parkin localizes to the Lewy bodies of Parkinson’s disease and dementia with Lewy bodies. Am J Pathol. 2002;160:1655–1667. doi: 10.1016/S0002-9440(10)61113-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
130.Mader I, Roser W, Kappos L, Hagberg G, Seelig J, Radue EW, et al. Serial proton MR spectroscopy of contrast-enhancing multiple sclerosis plaques: absolute metabolic values over 2 years during a clinical pharmacological study. AJNR Am J Neuroradiol. 2000;21:1220–1227. [PMC free article] [PubMed] [Google Scholar]
131.Arnold DL, Matthews PM, Francis G, Antel J. Proton magnetic resonance spectroscopy of human brainin vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med. 1990;14:154–159. doi: 10.1002/mrm.1910140115. [DOI] [PubMed] [Google Scholar]
132.Davie CA, Barker GJ, Thompson AJ, Tofts PS, McDonald WI, Miller DH. 1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1997;63:736–742. doi: 10.1136/jnnp.63.6.736. [DOI] [PMC free article] [PubMed] [Google Scholar]
133.Fu L, Matthews PM, De Stefano N, Worsley KJ, Narayanan S, Francis GS, et al. Imaging axonal damage of normal-appearing white matter in multiple sclerosis. Brain. 1998;121:103–113. doi: 10.1093/brain/121.1.103. [DOI] [PubMed] [Google Scholar]
134.Narayana PA, Doyle TJ, Lai D, Wolinsky JS. Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis. Ann Neurol. 1998;43:56–71. doi: 10.1002/ana.410430112. [DOI] [PubMed] [Google Scholar]
135.Arnold DL, Riess GT, Matthews PM, Francis GS, Collins DL, Wolfson C, et al. Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis. Ann Neurol. 1994;36:76–82. doi: 10.1002/ana.410360115. [DOI] [PubMed] [Google Scholar]
136.Lindon JC, Holmes E, Nicholson JK. Pattern recognition methods and applications in biomedical magnetic resonance. Prog NMR Spectrosc. 2001;39:1–40. [Google Scholar]
137.Nicholson JK, Higham DP, Timbrell JA, Sadler PJ. Quantitative high resolution 1H NMR urinalysis studies on the biochemical effects of cadmium in the rat. Mol Pharmacol. 1989;36:398–404. [PubMed] [Google Scholar]
138.Clayton TA, Lindon JC, Cloarec O, Antti H, Charuel C, Hanton G, et al. Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature. 2006;440:1073–1077. doi: 10.1038/nature04648. [DOI] [PubMed] [Google Scholar]
139.Ross BD, Hoang TQ, Bluml S, Dubowitz D, Kopyov OV, Jacques DB, et al. In vivo magnetic resonance spectroscopy of human fetal neural transplants. NMR Biomed. 1999;12:221–236. doi: 10.1002/(sici)1099-1492(199906)12:4<221::aid-nbm582>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
140.Baik HM, Choe BY, Lee HK, Suh TS, Son BC, Lee JM. Metabolic alterations in Parkinson’s disease after thalamotomy, as revealed by (1)H MR spectroscopy. Korean J Radiol. 2002;3:180–188. doi: 10.3348/kjr.2002.3.3.180. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
141.Baik HM, Choe BY, Son BC, Jeun SS, Kim MC, Lee KS, et al. Proton MR spectroscopic changes in Parkinson’s diseases after thalamotomy. Eur J Radiol. 2003;47:179–187. doi: 10.1016/s0720-048x(02)00211-5. [DOI] [PubMed] [Google Scholar]
142.Verbessern P, Lemiere J, Eijnde BO, Swinnen S, Vanhees L, van Leemputte M, et al. Creatine supplementation in Huntington’s disease: a placebo-controlled pilot trial. Neurology. 2003;61:925–930. doi: 10.1212/01.wnl.0000090629.40891.4b. [DOI] [PubMed] [Google Scholar]
143.Hersch SM, Gevorkian S, Marder K, Moskowitz C, Feigin A, Cox M, et al. Creatine in Huntington’s disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2′dG. Neurology. 2006;66:250–252. doi: 10.1212/01.wnl.0000194318.74946.b6. [DOI] [PubMed] [Google Scholar]
144.Tsang TM, Woodman B, McLoughlin G, Griffin JL, Tabrizi SJ, Bates GP, et al. Metabolic characterisation of the R6/2 transgenic mouse model of Huntington’s disease by high-resolution MAS 1H NMR spectroscopy. J Proteome Res. 2006;5:483–492. doi: 10.1021/pr050244o. [DOI] [PubMed] [Google Scholar]
145.Matthews RT, Yang L, Jenkins BG, Ferrante RJ, Rosen BR, Kaddurah-Daouk R, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. J Neurosci. 1998;18:156–163. doi: 10.1523/JNEUROSCI.18-01-00156.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
146.Tabrizi SJ, Blamire AM, Manners DN, Rajagopalan B, Styles P, Schapira AH, et al. Creatine therapy for Huntington’s disease: clinical and MRS findings in a 1-year pilot study. Neurology. 2003;61:141–142. doi: 10.1212/01.wnl.0000070186.97463.a7. [DOI] [PubMed] [Google Scholar]
147.Tsang TM, Huang JTJ, Holmes E, Bahn S. Metabolic profiling of plasma from discordant schizophrenia twins: correlation between lipid signals and global functioning in female schizophrenia patients. J Proteome Res. 2006;5:756–760. doi: 10.1021/pr0503782. [DOI] [PubMed] [Google Scholar]
148.Tkac I, Rao R, Georgieff MK, Gruetter R. Developmental and regional changes in the neurochemical profile of the rat brain determined by in vivo 1H NMR spectroscopy. Magn Reson Med. 2003;50:24–32. doi: 10.1002/mrm.10497. [DOI] [PubMed] [Google Scholar]
149.Dautry C, Vaufrey F, Brouillet E, Bizat N, Henry PG, Conde F, et al. Early N-acetylaspartate depletion is a marker of neuronal dysfunction in rats and primates chronically treated with the mitochondrial toxin 3-nitropropionic acid. J Cereb Blood Flow Metab. 2000;20:789–799. doi: 10.1097/00004647-200005000-00005. [DOI] [PubMed] [Google Scholar]
150.Matthews RT, Ferrante RJ, Klivenyi P, Yang L, Klein AM, Mueller G, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol. 1999;157:142–149. doi: 10.1006/exnr.1999.7049. [DOI] [PubMed] [Google Scholar]

[CR1] 1.Griffin JL, Sang E, Evens T, Davies K, Clarke K. Metabolic profiles of dystrophin and utrophin expression in mouse models of Duchenne muscular dystrophy. FEBS Lett. 2002;530:109–116. doi: 10.1016/s0014-5793(02)03437-3. [DOI] [PubMed] [Google Scholar]

[CR2] 2.Clish CB, Davidov E, Oresic M, Plasterer TN, Lavine G, Londo T, et al. Integrative biological analysis of the APOE*3-leiden transgenic mouse. Omics. 2004;8:3–13. doi: 10.1089/153623104773547453. [DOI] [PubMed] [Google Scholar]

[CR3] 3.Hwang D, Smith JJ, Leslie DM, Weston AD, Rust AG, Ramsey S, et al. A data integration methodology for systems biology: experimental verification. Proc Natl Acad Sci USA. 2005;102:17302–17307. doi: 10.1073/pnas.0508649102. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR4] 4.Miller RM, Federoff HJ. Microarrays in Parkinson’s disease: a systematic approach. NeuroRx. 2006;3:318–325. doi: 10.1016/j.nurx.2006.05.008. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR5] 5.Olson NE. The microarray data analysis process: from raw to biological significance. NeuroRx. 2006;3:371–381. doi: 10.1016/j.nurx.2006.05.005. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR6] 6.Nicholson JK, Lindon JC, Holmes E. ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica. 1999;29:1181–1189. doi: 10.1080/004982599238047. [DOI] [PubMed] [Google Scholar]

[CR7] 7.Nicholson JK, Connelly J, Lindon JC, Holmes E. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov. 2002;1:153–161. doi: 10.1038/nrd728. [DOI] [PubMed] [Google Scholar]

[CR8] 8.Fiehn O. Metabolomics: the link between genotypes and phenotypes. Plant Mol Biol. 2002;48:155–171. [PubMed] [Google Scholar]

[CR9] 9.Yang J, Xu G, Zheng Y, Kong H, Pang T, Lv S, et al. Diagnosis of liver cancer using HPLC-based metabonomics avoiding false-positive result from hepatitis and hepatocirrhosis diseases. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;813:59–65. doi: 10.1016/j.jchromb.2004.09.032. [DOI] [PubMed] [Google Scholar]

[CR10] 10.Odunsi K, Wollman RM, Ambrosone CB, Hutson A, McCann SE, Tammela J, et al. Detection of epithelial ovarian cancer using 1H-NMR-based metabonomics. Int J Cancer. 2005;113:782–788. doi: 10.1002/ijc.20651. [DOI] [PubMed] [Google Scholar]

[CR11] 11.Griffiths JR, Stubbs M. Opportunities for studying cancer by metabolomics: preliminary observations on tumors deficient in hypoxia-inducible factor 1. Adv Enzyme Regul. 2003;43:67–76. doi: 10.1016/s0065-2571(02)00030-4. [DOI] [PubMed] [Google Scholar]

[CR12] 12.Yang J, Xu G, Hong Q, Liebich HM, Lutz K, Schmulling RM, et al. Discrimination of Type 2 diabetic patients from healthy controls by using metabonomics method based on their serum fatty acid profiles. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;813:53–58. doi: 10.1016/j.jchromb.2004.09.023. [DOI] [PubMed] [Google Scholar]

[CR13] 13.Brindle JT, Antti H, Holmes E, Tranter G, Nicholson JK, Bethell HW, et al. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nat Med. 2002;8:1439–1444. doi: 10.1038/nm1202-802. [DOI] [PubMed] [Google Scholar]

[CR14] 14.Sabatine MS, Liu E, Morrow DA, Heller E, McCarroll R, Wiegand R, et al. Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation. 2005;112:3868–3875. doi: 10.1161/CIRCULATIONAHA.105.569137. [DOI] [PubMed] [Google Scholar]

[CR15] 15.Griffin JL, Cemal CK, Pook MA. Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3. Physiol Genomics. 2004;16:334–340. doi: 10.1152/physiolgenomics.00149.2003. [DOI] [PubMed] [Google Scholar]

[CR16] 16.Dunckley T, Coon KD, Stephan DA. Discovery and development of biomarkers of neurological disease. Drug Discov Today. 2005;10:326–334. doi: 10.1016/S1359-6446(04)03353-7. [DOI] [PubMed] [Google Scholar]

[CR17] 17.Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL, et al. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry. 2004;9:684–697. doi: 10.1038/sj.mp.4001511. [DOI] [PubMed] [Google Scholar]

[CR18] 18.Barshop BA. Metabolomic approaches to mitochondrial disease: correlation of urine organic acids. Mitochondrion. 2004;4:521–527. doi: 10.1016/j.mito.2004.07.010. [DOI] [PubMed] [Google Scholar]

[CR19] 19.Coen M, O’Sullivan M, Bubb WA, Kuchel PW, Sorrell T. Proton nuclear magnetic resonance-based metabonomics for rapid diagnosis of meningitis and ventriculitis. Clin Infect Dis. 2005;41:1582–1590. doi: 10.1086/497836. [DOI] [PubMed] [Google Scholar]

[CR20] 20.Braun KP, Gooskens RH, Vandertop WP, Tulleken CA, van der Grond J. 1H magnetic resonance spectroscopy in human hydro-cephalus. J Magn Reson Imaging. 2003;17:291–299. doi: 10.1002/jmri.10270. [DOI] [PubMed] [Google Scholar]

[CR21] 21.Wang Y, Holmes E, Nicholson JK, Cloarec O, Chollet J, Tanner M, et al. Metabonomic investigations in mice infected withSchistosoma mansoni: an approach for biomarker identification. Proc Natl Acad Sci USA. 2004;101:12676–12681. doi: 10.1073/pnas.0404878101. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR22] 22.Rudkin TM, Arnold DL. Proton magnetic resonance spectroscopy for the diagnosis and management of cerebral disorders. Arch Neurol. 1999;56:919–926. doi: 10.1001/archneur.56.8.919. [DOI] [PubMed] [Google Scholar]

[CR23] 23.Kapeller P, McLean MA, Griffin CM, Chard D, Parker GJ, Barker GJ, et al. Preliminary evidence for neuronal damage in cortical grey matter and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study. J Neurol. 2001;248:131–138. doi: 10.1007/s004150170248. [DOI] [PubMed] [Google Scholar]

[CR24] 24.Karrenbauer VD, Leoni V, Lim ET, Giovannoni G, Ingle GT, Sastre-Garriga J, et al. Plasma cerebrosterol and magnetic resonance imaging measures in multiple sclerosis. Clin Neurol Neurosurg. 2006;108:456–460. doi: 10.1016/j.clineuro.2005.07.010. [DOI] [PubMed] [Google Scholar]

[CR25] 25.Tartaglia MC, Arnold DL. The role of MRS and fMRI in multiple sclerosis. Adv Neurol. 2006;98:185–202. [PubMed] [Google Scholar]

[CR26] 26.Frisoni GB, Filippi M. Multiple sclerosis and Alzheimer’s disease through the looking glass of MR imaging. AJNR Am J Neuroradiol. 2005;26:2488–2491. [PMC free article] [PubMed] [Google Scholar]

[CR27] 27.Kleiner-Fisman G, Bergeron C, Lang AE. Presentation of Creutzfeldt—Jakob disease as acute corticobasal degeneration syndrome. Mov Disord. 2004;19:948–949. doi: 10.1002/mds.20140. [DOI] [PubMed] [Google Scholar]

[CR28] 28.Jenkins BG, Koroshetz WJ, Beal MF, Rosen BR. Evidence for impairment of energy metabolism in vivo in Huntington’s disease using localized 1H NMR spectroscopy. Neurology. 1993;43:2689–2695. doi: 10.1212/wnl.43.12.2689. [DOI] [PubMed] [Google Scholar]

[CR29] 29.Brouwer OF, Laboyrie PM, Peters AC, Vielvoye GJ. Follow-up magnetic resonance imaging in Hallervorden-Spatz disease. Clin Neurol Neurosurg. 1992;94:S57–S60. doi: 10.1016/0303-8467(92)90023-v. [DOI] [PubMed] [Google Scholar]

[CR30] 30.Kang PB, Hunter JV, Kaye EM. Lactic acid elevation in extra-mitochondrial childhood neurodegenerative diseases. J Child Neurol. 2001;16:657–660. doi: 10.1177/088307380101600906. [DOI] [PubMed] [Google Scholar]

[CR31] 31.Khiat A, Bard C, Lacroix A, Rousseau J, Boulanger Y. Brain metabolic alterations in Cushing’s syndrome as monitored by proton magnetic resonance spectroscopy. NMR Biomed. 1999;12:357–363. doi: 10.1002/(sici)1099-1492(199910)12:6<357::aid-nbm584>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]

[CR32] 32.Khiat A, Yared Z, Bard C, Lacroix A, Boulanger Y. Long-term brain metabolic alterations in exogenous Cushing’s syndrome as monitored by proton magnetic resonance spectroscopy. Brain Res. 2001;911:134–140. doi: 10.1016/s0006-8993(01)02697-x. [DOI] [PubMed] [Google Scholar]

[CR33] 33.Gallelli KA, Wagner CM, Karchemskiy A, Howe M, Spielman D, Reiss A, et al. N-acetylaspartate levels in bipolar offspring with and at high-risk for bipolar disorder. Bipolar Disord. 2005;7:589–597. doi: 10.1111/j.1399-5618.2005.00266.x. [DOI] [PubMed] [Google Scholar]

[CR34] 34.Choi IY, Lee SP, Guilfoyle DN, Helpern JA. In vivo NMR studies of neurodegenerative diseases in transgenic and rodent models. Neurochem Res. 2003;28:987–1001. doi: 10.1023/a:1023370104289. [DOI] [PubMed] [Google Scholar]

[CR35] 35.Li LM, Caramanos Z, Cendes F, Andermann F, Antel SB, Dubeau F, et al. Lateralization of temporal lobe epilepsy (TLE) and discrimination of TLE from extra-TLE using pattern analysis of magnetic resonance spectroscopic and volumetric data. Epilepsia. 2000;41:832–842. doi: 10.1111/j.1528-1157.2000.tb00250.x. [DOI] [PubMed] [Google Scholar]

[CR36] 36.Kalra S, Arnold DL, Cashman NR. Biological markers in the diagnosis and treatment of ALS. J Neurol Sci. 1999;165:S27–S32. doi: 10.1016/s0022-510x(99)00023-4. [DOI] [PubMed] [Google Scholar]

[CR37] 37.Matthews PM, Pioro E, Narayanan S, De Stefano N, Fu L, Francis G, et al. Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy. Brain. 1996;119:715–722. doi: 10.1093/brain/119.3.715. [DOI] [PubMed] [Google Scholar]

[CR38] 38.Seppi K, Schocke MF. An update on conventional and advanced magnetic resonance imaging techniques in the differential diagnosis of neurodegenerative parkinsonism. Curr Opin Neurol. 2005;18:370–375. doi: 10.1097/01.wco.0000173141.74137.63. [DOI] [PubMed] [Google Scholar]

[CR39] 39.Kasparova S, Sumbalova Z, Bystricky P, Kucharska J, Liptaj T, Mlynarik V, et al. Effect of coenzyme Q10 and vitamin E on brain energy metabolism in the animal model of Huntington’s disease. Neurochem Int. 2006;48:93–99. doi: 10.1016/j.neuint.2005.09.002. [DOI] [PubMed] [Google Scholar]

[CR40] 40.Fernandez A, Garcia-Segura JM, Ortiz T, Montoya J, Maestu F, Gil-Gregorio P, et al. Proton magnetic resonance spectroscopy and magnetoencephalographic estimation of delta dipole density: a combination of techniques that may contribute to the diagnosis of Alzheimer’s disease. Dement Geriatr Cogn Disord. 2005;20:169–177. doi: 10.1159/000087094. [DOI] [PubMed] [Google Scholar]

[CR41] 41.Pfefferbaum A, Adalsteinsson E, Spielman D, Sullivan EV, Lim KO. In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer’s disease. Arch Gen Psychiatry. 1999;56:185–192. doi: 10.1001/archpsyc.56.2.185. [DOI] [PubMed] [Google Scholar]

[CR42] 42.Preul MC, Caramanos Z, Collins DL, Villemure JG, Leblanc R, Olivier A, et al. Accurate, noninvasive diagnosis of human brain tumors by using proton magnetic resonance spectroscopy. Nat Med. 1996;2:323–325. doi: 10.1038/nm0396-323. [DOI] [PubMed] [Google Scholar]

[CR43] 43.Brown FF, Campbell ID, Kuchel PW, Rabenstein DC. Human erythrocyte metabolism studies by 1H spin echo NMR. FEBS Lett. 1977;82:12–16. doi: 10.1016/0014-5793(77)80875-2. [DOI] [PubMed] [Google Scholar]

[CR44] 44.Ohsaka A, Yoshikawa K, Matuhasi T. Detection by proton nuclear magnetic resonance of elevated lactate concentration in serums from patients with malignant tumors. Jpn J Med Sci Biol. 1979;32:305–309. doi: 10.7883/yoken1952.32.305. [DOI] [PubMed] [Google Scholar]

[CR45] 45.Bales JR, Higham DP, Howe I, Nicholson JK, Sadler PJ. Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin Chem. 1984;30:426–432. [PubMed] [Google Scholar]

[CR46] 46.Nicholson JK, Buckingham MJ, Sadler PJ. High resolution 1H n.m.r. studies of vertebrate blood and plasma. Biochem J. 1983;211:605–615. doi: 10.1042/bj2110605. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR47] 47.Nicholson JK, Timbrell JA, Sadler PJ. Proton NMR spectra of urine as indicators of renal damage: mercury-induced nephrotoxicity in rats. Mol Pharmacol. 1985;27:644–651. [PubMed] [Google Scholar]

[CR48] 48.Cheng LL, Newell K, Mallory AE, Hyman BT, Gonzalez RG. Quantification of neurons in Alzheimer and control brains with ex vivo high resolution magic angle spinning proton magnetic resonance spectroscopy and stereology. Magn Reson Imaging. 2002;20:527–533. doi: 10.1016/s0730-725x(02)00512-x. [DOI] [PubMed] [Google Scholar]

[CR49] 49.Cheng LL, Chang IW, Louis DN, Gonzalez RG. Correlation of high-resolution magic angle spinning proton magnetic resonance spectroscopy with histopathology of intact human brain tumor specimens. Cancer Res. 1998;58:1825–1832. [PubMed] [Google Scholar]

[CR50] 50.Cheng LL, Ma MJ, Becerra L, Ptak T, Tracey I, Lackner A, et al. Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc Natl Acad Sci USA. 1997;94:6408–6413. doi: 10.1073/pnas.94.12.6408. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR51] 51.Barton SJ, Howe FA, Tomlins AM, Cudlip SA, Nicholson JK, Bell BA, et al. Comparison of in vivo 1H MRS of human brain tumours with 1H HR-MAS spectroscopy of intact biopsy samplesin vitro. Magma. 1999;8:121–128. doi: 10.1007/BF02590529. [DOI] [PubMed] [Google Scholar]

[CR52] 52.Fu R, Brey WW, Shetty K, Gor’kov P, Saha S, Long JR, et al. Ultra-wide bore 900 MHz high-resolution NMR at the National High Magnetic Field Laboratory. J Magn Reson. 2005;177:1–8. doi: 10.1016/j.jmr.2005.07.013. [DOI] [PubMed] [Google Scholar]

[CR53] 53.Sidelmann UG, Braumann U, Hoffmann M, Spraul M, Lindon JC, Nicholson JK, et al. Directly coupled 800 MHz HPLC-NMR spectroscopy of urine and its applications to the identification of the major phase II metabolites of tolfenamic acid. Anal Chem. 1997;69:607–612. [Google Scholar]

[CR54] 54.Martin GE, Hadden CE, Russell DJ, Kaluzny BD, Guido JE, Duholke WK, et al. Identification of degradants of a complex alkaloid using NMR cryoprobe technology and ACD/structure elucidator. J Heterocyclic Chem. 2002;39:1241–1250. [Google Scholar]

[CR55] 55.Griffin JL, Lehtimaki KK, Valonen PK, Grohn OH, Kettunen MI, Yla-Herttuala S, et al. Assignment of (1)H nuclear magnetic resonance visible polyunsaturated fatty acids in BT4C gliomas undergoing ganciclovir-thymidine kinase gene therapy-induced programmed cell death. Cancer Res. 2003;63:3195–3201. [PubMed] [Google Scholar]

[CR56] 56.Hinse C, Richter C, Provenzani A, Stockigt J. In vivo monitoring of alkaloid metabolism in hybrid plant cell cultures by 2D cryo-NMR without labeling. Bioorg Med Chem. 2003;11:3913–3919. doi: 10.1016/s0968-0896(03)00430-9. [DOI] [PubMed] [Google Scholar]

[CR57] 57.Beckwith-Hall BM, Nicholson JK, Nicholls AW, Foxall PJ, Lindon JC, Connor SC, et al. Nuclear magnetic resonance spectroscopic and principal components analysis investigations into biochemical effects of three model hepatotoxins. Chem Res Toxicol. 1998;11:260–272. doi: 10.1021/tx9700679. [DOI] [PubMed] [Google Scholar]

[CR58] 58.Nicholson JK, Foxall PJ, Spraul M, Fanant RD, Lindon JC. 750 MHz 1H and 1H-13C NMR spectroscopy of human blood plasma. Anal Chem. 1995;67:793–811. doi: 10.1021/ac00101a004. [DOI] [PubMed] [Google Scholar]

[CR59] 59.Sathasivam K, Baxendale S, Mangiarini L, Bertaux F, Hetherington C, Kanazawa I, et al. Aberrant processing of the Fugu HD (FrHD) mRNA in mouse cells and in transgenic mice. Hum Mol Genet. 1997;6:2141–2149. doi: 10.1093/hmg/6.12.2141. [DOI] [PubMed] [Google Scholar]

[CR60] 60.Van Zijl PCM, O’Neil Johnson M, Mori S, Hurd RE. Magic-angle-gradient double-quantum-filtered COSY. J Magn Reson. 1995;113A:265–270. [Google Scholar]

[CR61] 61.Shockcor JP, Unger SE, Wilson ID, Foxall PJ, Nicholson JK, Lindon JC. Combined HPLC, NMR spectroscopy, and ion-trap mass spectrometry with application to the detection and characterization of xenobiotic and endogenous metabolites in human urine. Anal Chem. 1996;68:4431–4435. doi: 10.1021/ac9606463. [DOI] [PubMed] [Google Scholar]

[CR62] 62.Lindon JC, Nicholson JK, Holmes E, Keun HC, Craig A, Pearce JT, et al. Summary recommendations for standardization and reporting of metabolic analyses. Nat Biotechnol. 2005;23:833–838. doi: 10.1038/nbt0705-833. [DOI] [PubMed] [Google Scholar]

[CR63] 63.Garrod S, Humpher E, Connor SC, Connelly JC, Spraul M, Nicholson JK, et al. High-resolution (1)H NMR and magic angle spinning NMR spectroscopic investigation of the biochemical effects of 2-bromoethanamine in intact renal and hepatic tissue. Magn Reson Med. 2001;45:781–790. doi: 10.1002/mrm.1106. [DOI] [PubMed] [Google Scholar]

[CR64] 64.Moka D, Vorreuther R, Schicha H, Spraul M, Humpfer E, Lipinski M, et al. Biochemical classification of kidney carcinoma biopsy samples using magic-angle-spinning 1H nuclear magnetic resonance spectroscopy. J Pharm Biomed Anal. 1998;17:125–132. doi: 10.1016/s0731-7085(97)00176-3. [DOI] [PubMed] [Google Scholar]

[CR65] 65.Tomlins AM, Foxall PJ, Lynch MJ, Parkinson J, Everett JR, Nicholson JK. High resolution 1H NMR spectroscopic studies on dynamic biochemical processes in incubated human seminal fluid samples. Biochim Biophys Acta. 1998;1379:367–380. doi: 10.1016/s0304-4165(97)00116-5. [DOI] [PubMed] [Google Scholar]

[CR66] 66.Tate AR, Foxall PJ, Holmes E, Moka D, Spraul M, Nicholson JK, et al. Distinction between normal and renal cell carcinoma kidney cortical biopsy samples using pattern recognition of (1)H magic angle spinning (MAS) NMR spectra. NMR Biomed. 2000;13:64–71. doi: 10.1002/(sici)1099-1492(200004)13:2<64::aid-nbm612>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]

[CR67] 67.Eriksson L, Antti H, Gottfries J, Holmes E, Johansson E, Lindgren F, et al. Using chemometrics for navigating in the large data sets of genomics, proteomics, and metabonomics (gpm) Anal Bioanal Chem. 2004;380:419–429. doi: 10.1007/s00216-004-2783-y. [DOI] [PubMed] [Google Scholar]

[CR68] 68.Trygg J, Wold S. O2-PLS, a two-block (X-Y) latent variable regression (LVR) method with an integral OSC filter. J Chemometrics. 2003;17:53–64. [Google Scholar]

[CR69] 69.Turmaine M, Raza A, Mahal A, Mangiarini L, Bates GP, Davies SW. Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington’s disease. Proc Natl Acad Sci USA. 2000;97:8093–8097. doi: 10.1073/pnas.110078997. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR70] 70.Huang Y, Lisboa PJ, El-Deredy W. Tumour grading from magnetic resonance spectroscopy: a comparison of feature extraction with variable selection. Stat Med. 2003;22(1):147–164. doi: 10.1002/sim.1321. [DOI] [PubMed] [Google Scholar]

[CR71] 71.Cloarec O, Dumas ME, Trygg J, Craig A, Barton RH, Lindon JC, et al. Evaluation of the orthogonal projection on latent structure model limitations caused by chemical shift variability and improved visualization of biomarker changes in 1H NMR spectroscopic metabonomic studies. Anal Chem. 2005;77:517–526. doi: 10.1021/ac048803i. [DOI] [PubMed] [Google Scholar]

[CR72] 72.Ma’ayan A, Gardiner K, Iyengar R. The cognitive phenotype of Down syndrome: insights from intracellular network analysis. NeuroRx. 2006;3:394–403. doi: 10.1016/j.nurx.2006.05.036. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR73] 73.Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed. 2000;13:129–153. doi: 10.1002/1099-1492(200005)13:3<129::aid-nbm619>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]

[CR74] 74.Pfeuffer J, Tkac I, Provencher SW, Gruetter R. Toward an in vivo neurochemical profile: quantification of 18 metabolites in shortecho-time (1)H NMR spectra of the rat brain. J Magn Reson. 1999;141:104–120. doi: 10.1006/jmre.1999.1895. [DOI] [PubMed] [Google Scholar]

[CR75] 75.Tsang TM, Griffin JL, Haselden J, Fish C, Holmes E. Metabolic characterization of distinct neuroanatomical regions in rats by magic angle spinning 1H nuclear magnetic resonance spectroscopy. Magn Reson Med. 2005;53:1018–1024. doi: 10.1002/mrm.20447. [DOI] [PubMed] [Google Scholar]

[CR76] 76.Tsang TM, Woodman B, McLoughlin GA, Griffin JL, Tabrizi SJ, Bates GP, et al. Metabolic characterization of the R6/2 transgenic mouse model of Huntington’s disease by high-resolution MAS 1H NMR spectroscopy. J Proteome Res. 2006;5:483–492. doi: 10.1021/pr050244o. [DOI] [PubMed] [Google Scholar]

[CR77] 77.Griffin JL, Bollard M, Nicholson JK, Bhakoo K. Spectral profiles of cultured neuronal and glial cells derived from HRMAS (1)H NMR spectroscopy. NMR Biomed. 2002;15:375–384. doi: 10.1002/nbm.792. [DOI] [PubMed] [Google Scholar]

[CR78] 78.Urenjak J, Williams SR, Gadian DG, Noble M. Specific expression of N-acetylaspartate in neurons, oligodendrocyte-type-2 astrocyte progenitors, and immature oligodendrocytesin vitro. J Neurochem. 1992;59:55–61. doi: 10.1111/j.1471-4159.1992.tb08875.x. [DOI] [PubMed] [Google Scholar]

[CR79] 79.Hoang TQ, Bluml S, Dubowitz DJ, Moats R, Kopyov O, Jacques D, et al. Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington’s and Parkinson’s diseases. Neurology. 1998;50:1033–1040. doi: 10.1212/wnl.50.4.1033. [DOI] [PubMed] [Google Scholar]

[CR80] 80.Jenkins BG, Brouillet E, Chen YC, Storey E, Schulz JB, Kirschner P, et al. Non-invasive neurochemical analysis of focal excitotoxic lesions in models of neurodegenerative illness using spectroscopic imaging. J Cereb Blood Flow Metab. 1996;16:450–461. doi: 10.1097/00004647-199605000-00011. [DOI] [PubMed] [Google Scholar]

[CR81] 81.Jenkins BG, Rosas HD, Chen YC, Makabe T, Myers R, Mac-Donald M, et al. 1H NMR spectroscopy studies of Huntington’s disease: correlations with CAG repeat numbers. Neurology. 1998;50:1357–1365. doi: 10.1212/wnl.50.5.1357. [DOI] [PubMed] [Google Scholar]

[CR82] 82.Horska A, Naidu S, Herskovits EH, Wang PY, Kaufmann WE, Barker PB. Quantitative 1H MR spectroscopic imaging in early Rett syndrome. Neurology. 2000;54:715–722. doi: 10.1212/wnl.54.3.715. [DOI] [PubMed] [Google Scholar]

[CR83] 83.Lucetti C, Del Dotto P, Gambaccini G, Bernardini S, Bianchi MC, Tosetti M, et al. Proton magnetic resonance spectroscopy (1H-MRS) of motor cortex and basal ganglia in de novo Parkinson’s disease patients. Neurol Sci. 2001;22:69–70. doi: 10.1007/s100720170051. [DOI] [PubMed] [Google Scholar]

[CR84] 84.Tourbah A, Stievenart JL, Gout O, Fontaine B, Liblau R, Lubetzki C, et al. Localized proton magnetic resonance spectroscopy in relapsing remitting versus secondary progressive multiple sclerosis. Neurology. 1999;53:1091–1097. doi: 10.1212/wnl.53.5.1091. [DOI] [PubMed] [Google Scholar]

[CR85] 85.Pears MR, Cooper JD, Mitchison HM, Mortishire-Smith RJ, Pearce DA, Griffin JL. High resolution 1H NMR-based metabolomics indicates a neurotransmitter cycling deficit in cerebral tissue from a mouse model of Batten disease. J Biol Chem. 2005;280:42508–42514. doi: 10.1074/jbc.M507380200. [DOI] [PubMed] [Google Scholar]

[CR86] 86.Viant MR, Lyeth BG, Miller MG, Berman RF. An NMR metabolomic investigation of early metabolic disturbances following traumatic brain injury in a mammalian model. NMR Biomed. 2005;18:507–516. doi: 10.1002/nbm.980. [DOI] [PubMed] [Google Scholar]

[CR87] 87.Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R, et al. Parkinson’s disease in twins: an etiologic study. Jama. 1999;281:341–346. doi: 10.1001/jama.281.4.341. [DOI] [PubMed] [Google Scholar]

[CR88] 88.Weeks RA, Piccini P, Harding AE, Brooks DJ. Striatal D1 and D2 dopamine receptor loss in asymptomatic mutation carriers of Huntington’s disease. Ann Neurol. 1996;40:49–54. doi: 10.1002/ana.410400110. [DOI] [PubMed] [Google Scholar]

[CR89] 89.Sveinbjomsdottir S, Hicks AA, Jonsson T, Petursson H, Gugmundsson G, Frigge ML, et al. Familial aggregation of Parkinson’s disease in Iceland. N Engl J Med. 2000;343:1765–1770. doi: 10.1056/NEJM200012143432404. [DOI] [PubMed] [Google Scholar]

[CR90] 90.Bender A, Auer DP, Merl T, Reilmann R, Saemann P, Yassouridis A, et al. Creatine supplementation lowers brain glutamate levels in Huntington’s disease. J Neurol. 2005;252:36–41. doi: 10.1007/s00415-005-0595-4. [DOI] [PubMed] [Google Scholar]

[CR91] 91.Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–608. doi: 10.1038/33416. [DOI] [PubMed] [Google Scholar]

[CR92] 92.Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, et al. Ala30Pro mutation in the gene encoding α-synuclein in Parkinson’s disease. Nat Genet. 1998;18:106–108. doi: 10.1038/ng0298-106. [DOI] [PubMed] [Google Scholar]

[CR93] 93.Brouillet E, Hantraye P, Ferrante RJ, Dolan R, Leroy-Willig A, Kowall NW, et al. Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc Natl Acad Sci USA. 1995;92:7105–7109. doi: 10.1073/pnas.92.15.7105. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR94] 94.Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276:2045–2047. doi: 10.1126/science.276.5321.2045. [DOI] [PubMed] [Google Scholar]

[CR95] 95.Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2003;299:256–259. doi: 10.1126/science.1077209. [DOI] [PubMed] [Google Scholar]

[CR96] 96.Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44:595–600. doi: 10.1016/j.neuron.2004.10.023. [DOI] [PubMed] [Google Scholar]

[CR97] 97.Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science. 2004;304:1158–1160. doi: 10.1126/science.1096284. [DOI] [PubMed] [Google Scholar]

[CR98] 98.Klawans HL, Stein RW, Tanner CM, Goetz CG. A pure parkinsonian syndrome following acute carbon monoxide intoxication. Arch Neurol. 1982;39:302–304. doi: 10.1001/archneur.1982.00510170044012. [DOI] [PubMed] [Google Scholar]

[CR99] 99.Huang CC, Lu CS, Chu NS, Hochberg F, Lilienfeld D, Olanow W, et al. Progression after chronic manganese exposure. Neurology. 1993;43:1479–1483. doi: 10.1212/wnl.43.8.1479. [DOI] [PubMed] [Google Scholar]

[CR100] 100.Helmuth L. Neuroscience. Pesticide causes Parkinson’s in rats. Science. 2000;290:1068–1068. doi: 10.1126/science.290.5494.1068a. [DOI] [PubMed] [Google Scholar]

[CR101] 101.Langsten JW, Fomo LS, Rebert CS, Irwin I. Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey. Brain Res. 1984;292:390–394. doi: 10.1016/0006-8993(84)90777-7. [DOI] [PubMed] [Google Scholar]

[CR102] 102.Carlsson A, Lindqvist M, Magnusson T. 3,4-Dihydroxypheny-lalanine and 5-hydroxytryptophan as reserpine antagonists. Nature. 1957;180:1200–1200. doi: 10.1038/1801200a0. [DOI] [PubMed] [Google Scholar]

[CR103] 103.Ungerstedt U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol. 1968;5:107–110. doi: 10.1016/0014-2999(68)90164-7. [DOI] [PubMed] [Google Scholar]

[CR104] 104.Hastings TG, Lewis DA, Zigmond MJ. Role of oxidation in the neurotoxic effects of intrastriatal dopamine injections. Proc Natl Acad Sci USA. 1996;93:1956–1961. doi: 10.1073/pnas.93.5.1956. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR105] 105.Bloem BR, Irwin I, Buruma OJ, Haan J, Roos RA, Tetrud JW, et al. The MPTP model: versatile contributions to the treatment of idiopathic Parkinson’s disease. J Neurol Sci. 1990;97:273–293. doi: 10.1016/0022-510x(90)90225-c. [DOI] [PubMed] [Google Scholar]

[CR106] 106.Chen YC, Galpern WR, Brownell AL, Matthews RT, Bogdanov M, Isacson O, et al. Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: correlation with PET, micro-dialysis, and behavioral data. Magn Reson Med. 1997;38:389–398. doi: 10.1002/mrm.1910380306. [DOI] [PubMed] [Google Scholar]

[CR107] 107.Smith DA, Clarke LP, Fiedler JA, Murtagh FR, Bonaroti EA, Sengstock GJ, et al. Use of a clinical MR scanner for imaging the rat brain. Brain Res Bull. 1993;31:115–120. doi: 10.1016/0361-9230(93)90017-6. [DOI] [PubMed] [Google Scholar]

[CR108] 108.Boska MD, Lewis TB, Destache CJ, Benner EJ, Nelson JA, Uberti M, et al. Quantitative 1H magnetic resonance spectroscopic imaging determines therapeutic immunization efficacy in an animal model of Parkinson’s disease. J Neurosci. 2005;25:1691–1700. doi: 10.1523/JNEUROSCI.4364-04.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR109] 109.Brownell AL, Jenkins BG, Elmaleh DR, Deacon TW, Spealman RD, Isacson O. Combined PET/MRS brain studies show dynamic and long-term physiological changes in a primate model of Parkinson’s disease. Nat Med. 1998;4:1308–1312. doi: 10.1038/3300. [DOI] [PubMed] [Google Scholar]

[CR110] 110.Podell M, Hadjiconstantinou M, Smith MA, Neff NH. Proton magnetic resonance imaging and spectroscopy identify metabolic changes in the striatum in the MPTP feline model of parkinsonism. Exp Neurol. 2003;179:159–166. doi: 10.1016/s0014-4886(02)00015-8. [DOI] [PubMed] [Google Scholar]

[CR111] 111.Sperk G. Kainic acid seizures in the rat. Prog Neurobiol. 1994;42:1–32. doi: 10.1016/0301-0082(94)90019-1. [DOI] [PubMed] [Google Scholar]

[CR112] 112.Brouillet E, Conde F, Beal MF, Hantraye P. Replicating Huntington’s disease phenotype in experimental animals. Prog Neurobiol. 1999;59:427–468. doi: 10.1016/s0301-0082(99)00005-2. [DOI] [PubMed] [Google Scholar]

[CR113] 113.Dautry C, Conde F, Brouillet E, Mittoux V, Beal MF, Bloch G, et al. Serial 1H-NMR spectroscopy study of metabolic impairment in primates chronically treated with the succinate dehydrogenase inhibitor 3-nitropropionic acid. Neurobiol Dis. 1999;6:259–268. doi: 10.1006/nbdi.1999.0244. [DOI] [PubMed] [Google Scholar]

[CR114] 114.Palfi S, Conde F, Riche D, Brouillet E, Dautry C, Mittoux V, et al. Fetal striatal allografts reverse cognitive deficits in a primate model of Huntington’s disease. Nat Med. 1998;4:963–966. doi: 10.1038/nm0898-963. [DOI] [PubMed] [Google Scholar]

[CR115] 115.Mittoux V, Joseph JM, Conde F, Palfi S, Dautry C, Poyot T, et al. Restoration of cognitive and motor functions by ciliary neurotrophic factor in a primate model of Huntington’s disease. Hum Gene Ther. 2000;11:1177–1187. doi: 10.1089/10430340050015220. [DOI] [PubMed] [Google Scholar]

[CR116] 116.Garrod S, Bollard ME, Nicholls AW, Connor SC, Connelly J, Nicholson JK, et al. Integrated metabonomic analysis of the multiorgan effects of hydrazine toxicity in the rat. Chem Res Toxicol. 2005;18:115–122. doi: 10.1021/tx0498915. [DOI] [PubMed] [Google Scholar]

[CR117] 117.Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, et al. Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science. 2000;287:1265–1269. doi: 10.1126/science.287.5456.1265. [DOI] [PubMed] [Google Scholar]

[CR118] 118.Richfield EK, O’Brien CF, Eskin T, Shoulson I. Heterogeneous dopamine receptor changes in early and late Huntington’s disease. Neurosci Lett. 1991;132:121–126. doi: 10.1016/0304-3940(91)90448-3. [DOI] [PubMed] [Google Scholar]

[CR119] 119.Holowenko D, Peeling J, Sutherland G. 1H NMR properties of N-acetylaspartylglutamate in extracts of nervous tissue of the rat. NMR Biomed. 1992;5:43–47. doi: 10.1002/nbm.1940050108. [DOI] [PubMed] [Google Scholar]

[CR120] 120.van Dellen A, Welch J, Dixon RM, Cordery P, York D, Styles P, et al. N-acetylaspartate and DARPP-32 levels decrease in the corpus striatum of Huntington’s disease mice. NeuroReport. 2000;11:3751–3757. doi: 10.1097/00001756-200011270-00032. [DOI] [PubMed] [Google Scholar]

[CR121] 121.Jenkins BG, Klivenyi P, Kustermann E, Andreassen OA, Ferrante RJ, Rosen BR, et al. Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington’s disease mice. J Neurochem. 2000;74:2108–2119. doi: 10.1046/j.1471-4159.2000.0742108.x. [DOI] [PubMed] [Google Scholar]

[CR122] 122.Underwood BR, Broadhurst D, Dunn WB, Ellis DI, Michell AW, Vacher C, et al. Huntington’s disease patients and transgenic mice have similar pro-catabolic serum metabolite profiles. Brain. 2006;129:877–886. doi: 10.1093/brain/awl027. [DOI] [PubMed] [Google Scholar]

[CR123] 123.Henley SM, Bates GP, Tabrizi SJ. Biomarkers for neurodegenerative diseases. Curr Opin Neurol. 2005;18:698–705. doi: 10.1097/01.wco.0000186842.51129.cb. [DOI] [PubMed] [Google Scholar]

[CR124] 124.Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, et al. Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004;256:240–246. doi: 10.1111/j.1365-2796.2004.01380.x. [DOI] [PubMed] [Google Scholar]

[CR125] 125.DeCarli C. Mild cognitive impairment: prevalence, prognosis, aetiology, and treatment. Lancet Neurol. 2003;2:15–21. doi: 10.1016/s1474-4422(03)00262-x. [DOI] [PubMed] [Google Scholar]

[CR126] 126.Metastasio A, Rinaldi P, Tarducci R, Mariani E, Feliziani FT, Cherubim A, et al. Conversion of MCI to dementia: role of proton magnetic resonance spectroscopy. Neurobiol Aging. 2006;27:926–932. doi: 10.1016/j.neurobiolaging.2005.05.002. [DOI] [PubMed] [Google Scholar]

[CR127] 127.Frederick BD, Lyoo IK, Satlin A, Ahn KH, Kim MJ, Yurgelun-Todd DA, et al. In vivo proton magnetic resonance spectroscopy of the temporal lobe in Alzheimer’s disease. Prog Neuropsycho-pharmacol Biol Psychiatry. 2004;28:1313–1322. doi: 10.1016/j.pnpbp.2004.08.013. [DOI] [PubMed] [Google Scholar]

[CR128] 128.Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. α-synuclein in Lewy bodies. Nature. 1997;388:839–840. doi: 10.1038/42166. [DOI] [PubMed] [Google Scholar]

[CR129] 129.Schlossmacher MG, Frosch MP, Gai WP, Medina M, Sharma N, Fomo L, et al. Parkin localizes to the Lewy bodies of Parkinson’s disease and dementia with Lewy bodies. Am J Pathol. 2002;160:1655–1667. doi: 10.1016/S0002-9440(10)61113-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR130] 130.Mader I, Roser W, Kappos L, Hagberg G, Seelig J, Radue EW, et al. Serial proton MR spectroscopy of contrast-enhancing multiple sclerosis plaques: absolute metabolic values over 2 years during a clinical pharmacological study. AJNR Am J Neuroradiol. 2000;21:1220–1227. [PMC free article] [PubMed] [Google Scholar]

[CR131] 131.Arnold DL, Matthews PM, Francis G, Antel J. Proton magnetic resonance spectroscopy of human brainin vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med. 1990;14:154–159. doi: 10.1002/mrm.1910140115. [DOI] [PubMed] [Google Scholar]

[CR132] 132.Davie CA, Barker GJ, Thompson AJ, Tofts PS, McDonald WI, Miller DH. 1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1997;63:736–742. doi: 10.1136/jnnp.63.6.736. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR133] 133.Fu L, Matthews PM, De Stefano N, Worsley KJ, Narayanan S, Francis GS, et al. Imaging axonal damage of normal-appearing white matter in multiple sclerosis. Brain. 1998;121:103–113. doi: 10.1093/brain/121.1.103. [DOI] [PubMed] [Google Scholar]

[CR134] 134.Narayana PA, Doyle TJ, Lai D, Wolinsky JS. Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis. Ann Neurol. 1998;43:56–71. doi: 10.1002/ana.410430112. [DOI] [PubMed] [Google Scholar]

[CR135] 135.Arnold DL, Riess GT, Matthews PM, Francis GS, Collins DL, Wolfson C, et al. Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis. Ann Neurol. 1994;36:76–82. doi: 10.1002/ana.410360115. [DOI] [PubMed] [Google Scholar]

[CR136] 136.Lindon JC, Holmes E, Nicholson JK. Pattern recognition methods and applications in biomedical magnetic resonance. Prog NMR Spectrosc. 2001;39:1–40. [Google Scholar]

[CR137] 137.Nicholson JK, Higham DP, Timbrell JA, Sadler PJ. Quantitative high resolution 1H NMR urinalysis studies on the biochemical effects of cadmium in the rat. Mol Pharmacol. 1989;36:398–404. [PubMed] [Google Scholar]

[CR138] 138.Clayton TA, Lindon JC, Cloarec O, Antti H, Charuel C, Hanton G, et al. Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature. 2006;440:1073–1077. doi: 10.1038/nature04648. [DOI] [PubMed] [Google Scholar]

[CR139] 139.Ross BD, Hoang TQ, Bluml S, Dubowitz D, Kopyov OV, Jacques DB, et al. In vivo magnetic resonance spectroscopy of human fetal neural transplants. NMR Biomed. 1999;12:221–236. doi: 10.1002/(sici)1099-1492(199906)12:4<221::aid-nbm582>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]

[CR140] 140.Baik HM, Choe BY, Lee HK, Suh TS, Son BC, Lee JM. Metabolic alterations in Parkinson’s disease after thalamotomy, as revealed by (1)H MR spectroscopy. Korean J Radiol. 2002;3:180–188. doi: 10.3348/kjr.2002.3.3.180. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]

[CR141] 141.Baik HM, Choe BY, Son BC, Jeun SS, Kim MC, Lee KS, et al. Proton MR spectroscopic changes in Parkinson’s diseases after thalamotomy. Eur J Radiol. 2003;47:179–187. doi: 10.1016/s0720-048x(02)00211-5. [DOI] [PubMed] [Google Scholar]

[CR142] 142.Verbessern P, Lemiere J, Eijnde BO, Swinnen S, Vanhees L, van Leemputte M, et al. Creatine supplementation in Huntington’s disease: a placebo-controlled pilot trial. Neurology. 2003;61:925–930. doi: 10.1212/01.wnl.0000090629.40891.4b. [DOI] [PubMed] [Google Scholar]

[CR143] 143.Hersch SM, Gevorkian S, Marder K, Moskowitz C, Feigin A, Cox M, et al. Creatine in Huntington’s disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2′dG. Neurology. 2006;66:250–252. doi: 10.1212/01.wnl.0000194318.74946.b6. [DOI] [PubMed] [Google Scholar]

[CR144] 144.Tsang TM, Woodman B, McLoughlin G, Griffin JL, Tabrizi SJ, Bates GP, et al. Metabolic characterisation of the R6/2 transgenic mouse model of Huntington’s disease by high-resolution MAS 1H NMR spectroscopy. J Proteome Res. 2006;5:483–492. doi: 10.1021/pr050244o. [DOI] [PubMed] [Google Scholar]

[CR145] 145.Matthews RT, Yang L, Jenkins BG, Ferrante RJ, Rosen BR, Kaddurah-Daouk R, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. J Neurosci. 1998;18:156–163. doi: 10.1523/JNEUROSCI.18-01-00156.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR146] 146.Tabrizi SJ, Blamire AM, Manners DN, Rajagopalan B, Styles P, Schapira AH, et al. Creatine therapy for Huntington’s disease: clinical and MRS findings in a 1-year pilot study. Neurology. 2003;61:141–142. doi: 10.1212/01.wnl.0000070186.97463.a7. [DOI] [PubMed] [Google Scholar]

[CR147] 147.Tsang TM, Huang JTJ, Holmes E, Bahn S. Metabolic profiling of plasma from discordant schizophrenia twins: correlation between lipid signals and global functioning in female schizophrenia patients. J Proteome Res. 2006;5:756–760. doi: 10.1021/pr0503782. [DOI] [PubMed] [Google Scholar]

[CR148] 148.Tkac I, Rao R, Georgieff MK, Gruetter R. Developmental and regional changes in the neurochemical profile of the rat brain determined by in vivo 1H NMR spectroscopy. Magn Reson Med. 2003;50:24–32. doi: 10.1002/mrm.10497. [DOI] [PubMed] [Google Scholar]

[CR149] 149.Dautry C, Vaufrey F, Brouillet E, Bizat N, Henry PG, Conde F, et al. Early N-acetylaspartate depletion is a marker of neuronal dysfunction in rats and primates chronically treated with the mitochondrial toxin 3-nitropropionic acid. J Cereb Blood Flow Metab. 2000;20:789–799. doi: 10.1097/00004647-200005000-00005. [DOI] [PubMed] [Google Scholar]

[CR150] 150.Matthews RT, Ferrante RJ, Klivenyi P, Yang L, Klein AM, Mueller G, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol. 1999;157:142–149. doi: 10.1006/exnr.1999.7049. [DOI] [PubMed] [Google Scholar]

PERMALINK

The application of NMR-based metabonomics in neurological disorders

Elaine Holmes

Tsz M Tsang

Sarah J Tabrizi

Summary

References

ACTIONS

PERMALINK

RESOURCES

Cite

Add to Collections

PERMALINK

The application of NMR-based metabonomics in neurological disorders

Elaine Holmes

Tsz M Tsang

Sarah J Tabrizi

Summary

References

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases