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Iodoacetate Produces Striatal Excitotoxic Lesions
Author(s) -
Matthews Russell T.,
Ferrante Robert J.,
Jenkins Bruce G.,
Browne Susan E.,
Goetz Katrine,
Berger Stephanie,
Chen Iris Y.C.,
Beal M. Flint
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69010285.x
Subject(s) - neuroscience , striatum , chemistry , biology , dopamine
Impairment of energy production may play a role in the pathogenesis of Huntington's disease (HD). It was recently shown that huntingtin can bind to and possibly inhibit the glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH). We found that intrastriatal administration of the GAPDH inhibitor iodoacetate produces striatal lesions that are significantly attenuated by removal of the corticostriatal glutamatergic input, consistent with an excitotoxic mechanism. The lesions are accompanied by increased production of hydroxyl free radicals as assessed by conversion of salicylate to 2,3‐ and 2,5‐dihydroxybenzoic acid. In vivo magnetic resonance imaging showed lesions on T 2 ‐weighted scans, but there was only a small increase in lactate content. These results show that inhibition of GAPDH produces striatal lesions in vivo and suggest that inhibition of GAPDH could contribute to neuronal degeneration in HD.