Skip to main content
NCBI home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1991 Nov;54(11):984–988. doi: 10.1136/jnnp.54.11.984

Amyotrophic lateral sclerosis: glutamate dehydrogenase and transmitter amino acids in the spinal cord.

S Malessa 1, P N Leigh 1, O Bertel 1, E Sluga 1, O Hornykiewicz 1
PMCID: PMC1014621  PMID: 1686899

Abstract

Measurements were taken of the activity of glutamate dehydrogenase (GDH) and the levels of transmitter amino acids in anatomically dissected regions of cervical and lumbar spinal cord in eight patients dying with amyotrophic lateral sclerosis (ALS) and in 11 neurologically normal controls. GDH activity was considerably increased in lateral and ventral white matter and in the dorsal horn of the ALS cervical spinal cord, but normal in the ventral horn and the dorsal columns. Similar, although less pronounced, GDH changes were found in the lumbar enlargement. The mean concentrations of aspartate and glutamate were reduced in all regions of ALS spinal cord investigated. Taurine concentrations were significantly increased in several subdivisions of cervical spinal cord, but normal in lumbar regions. Glycine levels were significantly reduced in lumbar ventral and dorsal horns. There was no striking change in spinal cord GABA levels in our ALS patients. It is suggested that the reduced levels of glutamate and aspartate as well as the elevated GDH activity in the spinal cord of ALS patients may reflect an overactivity of the neurons releasing these potentially excitotoxic amino acids and thus may be causally related to the spinal neuro-degenerative changes characteristic of ALS.

Full text

PDF
984

Images in this article

985Image
on p.985

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aoki C., Milner T. A., Sheu K. F., Blass J. P., Pickel V. M. Regional distribution of astrocytes with intense immunoreactivity for glutamate dehydrogenase in rat brain: implications for neuron-glia interactions in glutamate transmission. J Neurosci. 1987 Jul;7(7):2214–2231. doi: 10.1523/JNEUROSCI.07-07-02214.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aubby D., Saggu H. K., Jenner P., Quinn N. P., Harding A. E., Marsden C. D. Leukocyte glutamate dehydrogenase activity in patients with degenerative neurological disorders. J Neurol Neurosurg Psychiatry. 1988 Jul;51(7):893–902. doi: 10.1136/jnnp.51.7.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bird E. D., Gale J. S., Spokes E. G. Huntington's chorea: post mortem activity of enzymes involved in cerebral glucose metabolism. J Neurochem. 1977 Sep;29(3):539–545. doi: 10.1111/j.1471-4159.1977.tb10703.x. [DOI] [PubMed] [Google Scholar]
  4. Chee P. Y., Dahl J. L., Fahien L. A. The purification and properties of rat brain glutamate dehydrogenase. J Neurochem. 1979 Jul;33(1):53–60. doi: 10.1111/j.1471-4159.1979.tb11705.x. [DOI] [PubMed] [Google Scholar]
  5. Duvoisin R. C., Chokroverty S., Lepore F., Nicklas W. Glutamate dehydrogenase deficiency in patients with olivopontocerebellar atrophy. Neurology. 1983 Oct;33(10):1322–1326. doi: 10.1212/wnl.33.10.1332. [DOI] [PubMed] [Google Scholar]
  6. Duvoisin R. C., Nicklas W. J., Ritchie V., Sage J., Chokroverty S. Low leukocyte glutamate dehydrogenase activity does not correlate with a particular type of multiple system atrophy. J Neurol Neurosurg Psychiatry. 1988 Dec;51(12):1508–1511. doi: 10.1136/jnnp.51.12.1508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Finocchiaro G., Taroni F., Di Donato S. Glutamate dehydrogenase in olivopontocerebellar atrophies: leukocytes, fibroblasts, and muscle mitochondria. Neurology. 1986 Apr;36(4):550–553. doi: 10.1212/wnl.36.4.550. [DOI] [PubMed] [Google Scholar]
  8. Gillberg P. G., Aquilonius S. M., Eckernäs S. A., Lundqvist G., Winblad B. Choline acetyltransferase and substance P-like immuno-reactivity in the human spinal cord: changes in amyotrophic lateral sclerosis. Brain Res. 1982 Nov 4;250(2):394–397. doi: 10.1016/0006-8993(82)90439-5. [DOI] [PubMed] [Google Scholar]
  9. Hugon J., Tabaraud F., Rigaud M., Vallat J. M., Dumas M. Glutamate dehydrogenase and aspartate aminotransferase in leukocytes of patients with motor neuron disease. Neurology. 1989 Jul;39(7):956–958. doi: 10.1212/wnl.39.7.956. [DOI] [PubMed] [Google Scholar]
  10. Hugon J., Vallat J. M., Spencer P. S., Leboutet M. J., Barthe D. Kainic acid induces early and delayed degenerative neuronal changes in rat spinal cord. Neurosci Lett. 1989 Oct 9;104(3):258–262. doi: 10.1016/0304-3940(89)90585-5. [DOI] [PubMed] [Google Scholar]
  11. Kaneko T., Akiyama H., Mizuno N. Immunohistochemical demonstration of glutamate dehydrogenase in astrocytes. Neurosci Lett. 1987 Jun 15;77(2):171–175. doi: 10.1016/0304-3940(87)90581-7. [DOI] [PubMed] [Google Scholar]
  12. Marchi M., Bocchieri P., Garbarino L., Raiteri M. Muscarinic inhibition of endogenous glutamate release from rat hippocampus synaptosomes. Neurosci Lett. 1989 Jan 16;96(2):229–234. doi: 10.1016/0304-3940(89)90063-3. [DOI] [PubMed] [Google Scholar]
  13. Marchi M., Raiteri M. Interaction acetylcholine-glutamate in rat hippocampus: involvement of two subtypes of M-2 muscarinic receptors. J Pharmacol Exp Ther. 1989 Mar;248(3):1255–1260. [PubMed] [Google Scholar]
  14. Nagata Y., Okuya M., Watanabe R., Honda M. Regional distribution of cholinergic neurons in human spinal cord transections in the patients with and without motor neuron disease. Brain Res. 1982 Jul 29;244(2):223–229. doi: 10.1016/0006-8993(82)90081-6. [DOI] [PubMed] [Google Scholar]
  15. OSTERBERG K. A., WATTENBERG L. W. Oxidative histochemistry of reactive astrocytes. Arch Neurol. 1962 Sep;7:211–218. doi: 10.1001/archneur.1962.04210030049007. [DOI] [PubMed] [Google Scholar]
  16. Perry T. L., Hansen S., Gandham S. S. Postmortem changes of amino compounds in human and rat brain. J Neurochem. 1981 Feb;36(2):406–410. doi: 10.1111/j.1471-4159.1981.tb01608.x. [DOI] [PubMed] [Google Scholar]
  17. Perry T. L., Hansen S., Jones K. Brain glutamate deficiency in amyotrophic lateral sclerosis. Neurology. 1987 Dec;37(12):1845–1848. doi: 10.1212/wnl.37.12.1845. [DOI] [PubMed] [Google Scholar]
  18. Plaitakis A., Berl S., Yahr M. D. Neurological disorders associated with deficiency of glutamate dehydrogenase. Ann Neurol. 1984 Feb;15(2):144–153. doi: 10.1002/ana.410150206. [DOI] [PubMed] [Google Scholar]
  19. Plaitakis A., Caroscio J. T. Abnormal glutamate metabolism in amyotrophic lateral sclerosis. Ann Neurol. 1987 Nov;22(5):575–579. doi: 10.1002/ana.410220503. [DOI] [PubMed] [Google Scholar]
  20. Plaitakis A., Constantakakis E., Smith J. The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosis. Ann Neurol. 1988 Sep;24(3):446–449. doi: 10.1002/ana.410240314. [DOI] [PubMed] [Google Scholar]
  21. Robinson N. Chemical changes in the spinal cord in Friedreich's ataxia and motor neurone disease. J Neurol Neurosurg Psychiatry. 1968 Aug;31(4):330–333. doi: 10.1136/jnnp.31.4.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schmid R., Hong J. S., Meek J., Costa E. The effect of kainic acid on the hippocampal content of putative transmitter amino acids. Brain Res. 1980 Nov 3;200(2):355–362. doi: 10.1016/0006-8993(80)90926-9. [DOI] [PubMed] [Google Scholar]
  23. Swash M., Leader M., Brown A., Swettenham K. W. Focal loss of anterior horn cells in the cervical cord in motor neuron disease. Brain. 1986 Oct;109(Pt 5):939–952. doi: 10.1093/brain/109.5.939. [DOI] [PubMed] [Google Scholar]
  24. Yoshino Y., Koike H., Akai K. Free amino acids in motor cortex of amyotrophic lateral sclerosis. Experientia. 1979 Feb 15;35(2):219–220. doi: 10.1007/BF01920627. [DOI] [PubMed] [Google Scholar]
  25. de Belleroche J., Recordati A., Rose F. C. Elevated levels of amino acids in the CSF of motor neuron disease patients. Neurochem Pathol. 1984 Spring;2(1):1–6. doi: 10.1007/BF02834167. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES