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. 2011 Jun 4;27(3):143–155. doi: 10.1007/s12264-011-1028-2

Combined administration of D-galactose and aluminium induces Alzheimerlike lesions in brain

D- 半乳糖和铝联合应用诱导大脑产生阿尔茨海默病样损伤

Fei Xiao 1, Xiao-Guang Li 2,3, Xiao-Yu Zhang 1, Jun-Dai Hou 1, Lian-Feng Lin 1, Qin Gao 2,3,✉, Huan-Min Luo 1,2,3
PMCID: PMC5560362  PMID: 21614097

Abstract

Objective

It has been reported that D-galactose (D-gal) can model subacute aging, and aluminum (Al) acts as a neurotoxin, but combined effects of them have not been reported. The present work aimed to reveal the effect of combined administration of D-gal and Al in mice and compare the effect of D-gal treatment with that of Al treatment.

Methods

Al was intragastrically administered and D-gal was subcutaneously injected into Kunming mice for 10 consecutive weeks. Learning and memory, cholinergic systems, as well as protein levels of amyloid β (Aβ) and hyperphosphorylated tau were determined using Morri water maze test, biochemical assays and immunohistochemical staining, respectively.

Results

The mice with combined treatment had obvious learning and memory deficits, and showed decreases in brain acetylcholine (ACh) level and in activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Formation of senile plaque (SP)-like and neurofibrillary tangle (NFT)-like structures was also observed. The behavioral and pathological changes persisted for at least 6 weeks after withdrawal of D-gal and Al.

Conclusion

Combined use of D-gal and Al is an effective way to establish the non-transgenic Alzheimer’s disease (AD) animal model, and is useful for studies of AD pathogenesis and therapeutic evaluation.

Keywords: Alzheimer’s disease, brain change, D-galactose, aluminum, neurodegenerative disease, animal model

Footnotes

These authors contributed equally to this work.

References

  • [1].Whitehouse P.J., Price D.L., Struble R.G., Clark A.W., Coyle J.T., Delon M.R. Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science. 1982;215(4537):1237–1239. doi: 10.1126/science.7058341. [DOI] [PubMed] [Google Scholar]
  • [2].Selkoe D.J. Alzheimer’s disease: Genes, proteins, and therapy. Physiological Rev. 2001;81(2):741–766. doi: 10.1152/physrev.2001.81.2.741. [DOI] [PubMed] [Google Scholar]
  • [3].Duff K., Hardy J. Alzheimer’s disease: mouse model made. Nature. 1995;373(6514):476–477. doi: 10.1038/373476a0. [DOI] [PubMed] [Google Scholar]
  • [4].Kawabata S., Higgins G.A., Gordon J.W. Amyloid plaques, neurofibrillary tangles and neuronal loss in brains of transgenic mice overexpressing a C-terminal fragment of human amyloid precursor protein. Nature. 1991;354(6353):476–478. doi: 10.1038/354476a0. [DOI] [PubMed] [Google Scholar]
  • [5].Quon D., Wang Y., Catalano R., Scardina J.M., Murakami K., Cordell B. Formation of beta-amyloid protein deposits in brains of transgenic mice. Nature. 1991;352(6332):239–241. doi: 10.1038/352239a0. [DOI] [PubMed] [Google Scholar]
  • [6].Ho S.C., Liu J.H., Wu R.Y. Establishment of the mimetic aging effect in mice caused by D-galactose. Biogerontology. 2003;4(1):15–18. doi: 10.1023/A:1022417102206. [DOI] [PubMed] [Google Scholar]
  • [7].Zhang Q., Li X., Cui X., Zuo P. D-galactose injured neurogenesis in the hippocampus of adult mice. Neurol Res. 2005;27(5):552–556. doi: 10.1179/016164105X25126. [DOI] [PubMed] [Google Scholar]
  • [8].Wei H., Li L., Song Q., Ai H., Chu J., Li W. Behavioural study of the D-galactose induced aging model in C57BL/6J mice. Behav Brain Res. 2005;57(2):245–251. doi: 10.1016/j.bbr.2004.07.003. [DOI] [PubMed] [Google Scholar]
  • [9].Cui X., Wang L., Zuo P., Han Z., Fang Z., Li W., et al. D-galactosecaused life shortening in Drosophila melanogaster and Musca domestica is associated with oxidative stress. Biogerontology. 2004;5(5):317–325. doi: 10.1007/s10522-004-2570-3. [DOI] [PubMed] [Google Scholar]
  • [10].Ida H., Ishibashi K., Reiser K., Hjelmeland L.M., Handa J.T. Ultrastructural aging of the RPE-Bruch’s membrane-choriocapillaris complex in the D-galactose-treated mouse. Invest Ophthalmol Vis Sci. 2004;45(7):2348–2354. doi: 10.1167/iovs.03-1337. [DOI] [PubMed] [Google Scholar]
  • [11].Song X., Bao M., Li D., Li Y.M. Advanced glycation in D-galactoseinduced mouse aging model. Mech Ageing Dev. 1999;108(3):239–251. doi: 10.1016/S0047-6374(99)00022-6. [DOI] [PubMed] [Google Scholar]
  • [12].Moumen R., Ait-Oukhatar N., Bureau F., Fleury C., Bouglé D., Arhan P., et al. Aluminium increases xanthine oxidase activity and disturbs antioxidant status in the rat. J Trace Elem Med Biol. 2001;15(2–3):89–93. doi: 10.1016/S0946-672X(01)80049-3. [DOI] [PubMed] [Google Scholar]
  • [13].Platt B., Fiddler G., Riedel G., Henderson Z. Aluminium toxicity in the rat brain: histochemical and immunocytochemical evidence. Brain Res Bull. 2001;55(2):257–267. doi: 10.1016/S0361-9230(01)00511-1. [DOI] [PubMed] [Google Scholar]
  • [14].Boni U.D., Otvos A., Scott J.W., Crapper D.R. Neurofibrillary degeneration induced by systemic aluminum. Acta Neuropathol (Berl) 1976;35(4):285–294. [PubMed] [Google Scholar]
  • [15].Muller J.P., Bruinink A. Neurotoxic effects of aluminium on embryonic chick brain cultures. Acta Neuropathol (Berl) 1994;88(4):359–366. doi: 10.1007/BF00310380. [DOI] [PubMed] [Google Scholar]
  • [16].Hermenegildo C., Saez R., Minoia C., Manzo L., Felipo V. Chronic exposure to aluminium impairs the glutamate-nitric oxide-cyclic GMP pathway in the rat in vivo. Neurochem Int. 1999;34(3):245–253. doi: 10.1016/S0197-0186(99)00010-8. [DOI] [PubMed] [Google Scholar]
  • [17].Henderson A.S. Epidemiology of dementia disorders. In: Wurtman R.J., Corkin S., Growdon J.H., Ritter-Walker E., editors. Alzheimer’s disease. Vol. 51 Advances in neurology. New York: Raven Press; 1990. pp. 15–25. [PubMed] [Google Scholar]
  • [18].Luo H.M., Xiao F. Alzheimer-like pathological changes of mice induced by D-galactose and aluminum trichloride. Chin J Pharmacol Toxicol. 2004;18(1):22–26. [Google Scholar]
  • [19].Luo HM, Xiao F. Preparing method for Alzheimer disease animal model [P]. CN, CN1278603.2006-10-11.
  • [20].Litchfield S., Nagy Z. New temperature modification makes the Bielschowsky silver stain reproducible. Acta Neuropathologica. 2001;101(1):17–21. doi: 10.1007/s004010000248. [DOI] [PubMed] [Google Scholar]
  • [21].Andrasi E., Pali N., Molnar Z., Kösel S. Brain aluminum, magnesium and phosphorus contents of control and Alzheimer-diseased patients. J Alzheimers Dis. 2005;7(4):273–284. doi: 10.3233/jad-2005-7402. [DOI] [PubMed] [Google Scholar]
  • [22].Fattoretti P., Bertoni-Freddari C., Balietti M., Giorgetti B., Solazzi M., Zatta P. Chronic aluminum administration to old rats results in increased levels of brain metalions and enlarged hippocampal mossy fibers. Ann N Y Acad Sci. 2004;1019(8):44–47. doi: 10.1196/annals.1297.010. [DOI] [PubMed] [Google Scholar]
  • [23].Deloncle R., Guillard O. Mechanism of Alzheimer’s disease: arguments for a neurotransmitter-aluminium complex implication. Neurochem Res. 1990;15(12):1239–1245. doi: 10.1007/BF01208586. [DOI] [PubMed] [Google Scholar]
  • [24].McLachlan D.R., Lukiw W.J., Cho H.J., Carp R.I., Wisniewski H. Chromatin structure in scrapie and Alzheimer’s disease. Can J Neurol Sci. 1986;13(4Suppl):427–431. doi: 10.1017/s0317167100037057. [DOI] [PubMed] [Google Scholar]
  • [25].Yokel R.A. Aluminum produces age related behavioral toxicity in the rabbit. Neurotoxicol Teratol. 1989;11(3):237–242. doi: 10.1016/0892-0362(89)90065-2. [DOI] [PubMed] [Google Scholar]
  • [26].Guo G.W., Wu Y.L., Yang X.H., Guo L.N., Yang Y.X. Effects of aluminum chloride on amyloid β-protein precursor and glial fibrillary acidic protein expression in rat cortex. Chin J Pharmacol Toxicol. 1999;13(3):227–230. [Google Scholar]
  • [27].Qian Y.H., Yang J., Ren H.M., Hu H.T., Zhang Z.J. Immunocytochemical study of amyloid protein accumulation in dorsal hippocampal formation of a rat model of dementia. J Xian Medi Univ. 1997;18(3):304–307. [Google Scholar]
  • [28].McLachlan D.R., Kruck T.P., Lukiw W.J., Krishnan S.S. Would decreased aluminum ingestion reduce the incidence of Alzheimer’s disease? CMAJ. 1991;145(7):793–804. [PMC free article] [PubMed] [Google Scholar]
  • [29].Pepeu G., Giovannini M.G. Changes in acetylcholine extracellular levels during cognitive processes. Learn Mem. 2004;11(1):21–27. doi: 10.1101/lm.68104. [DOI] [PubMed] [Google Scholar]

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