The cortical lesion of Huntington's disease: Further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N‐methyl‐D‐aspartate lesions of rat cortex
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AbstractHuntingtons's disease is a progressive neurodegenerative disease in which the basal ganglia are preferentially affected. Recent evidence, however, suggests involvement of the cerebral cortex as well, with sparing of neurochemically defined subsets of gamma‐aminobutyric acid (GABA)‐ergic interneurons. In the present study, we examined changes in concentrations of the amino acid neurotransmitters GABA, glutamate, and aspartate in nine cortical regions from 23 patients with advanced Huntington's disease and 12 control brains. GABA concentrations were significantly increased in eight of the nine regions, consistent with a sparing of GABAergic local circuit neurons in the context of progressive cortical atrophy. Small but significant increases in glutamate were found in six of the nine regions, while aspartate levels were generally unaffected. Striate cortex (Brodmann's area 17) showed the most profound increases in GABA and glutamate. We also investigated the effects of powdering the excitotoxins N‐methyl‐D‐aspartate (NMDA) or kainic acid onto the dura of rats. The resulting lesions were examined at 1 week and 6 months. The NMDA‐induced lesions showed striking sparing of parvalbumin‐positive neurons (a subset of GABAergic interneurons), and this sparing was reflected in neurochemical measurements of GABA; kainic acid lesions failed to display this selectivity. Somatostatin, cholecystokinin, and vasoactive intestinal polypeptide concentrations were spared by the NMDA‐induced lesions, and substance P levels were significantly increased. These results provide evidence that NMDA excitotoxic lesions of cerebral cortex can produce a selective pattern of neuronal damage similar to that which occurs in Huntington's disease.
