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What excitotoxin kills striatal neurons in Huntington's disease? Clues from neurochemical studies

T L Perry1, S Hansen

  • 1Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.

Neurology
|January 1, 1990
PubMed

Insights

Huntington's disease (HD) is linked to decreased glutamate in the brain and increased glutamate in cerebrospinal fluid (CSF). Researchers suggest glutamate may be a neurotoxin in HD due to impaired reuptake.

Area of Science:

  • Neuroscience
  • Neurochemistry
  • Neurology

Background:

  • Huntington's disease (HD) is a progressive neurodegenerative disorder.
  • The exact neurochemical mechanisms underlying HD pathogenesis remain incompletely understood.

Purpose of the Study:

  • To investigate the role of amino acids, particularly glutamate, in the pathophysiology of Huntington's disease.
  • To explore potential excitotoxic mechanisms contributing to striatal degeneration in HD.

Main Methods:

  • Amino acid analysis of post-mortem caudate nucleus and putamen tissues from HD patients and controls.
  • Measurement of amino acid concentrations in the cerebrospinal fluid (CSF) of living HD patients and controls.

Main Results:

  • Significantly decreased mean glutamate content was observed in the caudate nucleus and putamen of HD patients.
  • Significantly increased mean glutamate concentration was found in the CSF of living HD patients compared to controls.
  • Amino acids such as aspartic acid, proline, 5-oxoproline, homocysteic acid, glycine, and glutathione were investigated and found unlikely to be causative excitotoxins in HD.

Conclusions:

  • Glutamic acid is suggested as a potential proximate causative neurotoxin in the striatum in Huntington's disease.
  • An unexplained failure in the reuptake mechanism for released glutamate in the striatum may underlie its neurotoxic effects in HD.

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