1670782

Neurochemical characterization of excitotoxin lesions in the cerebral cortex.

Article date: 1991/1/1

PubMed ID: 1670782

Journal name: The Journal of neuroscience : the official journal of the Society for Neuroscience (ISSN: 0270-6474)

ABSTRACT

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.

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Author List: Beal M F, Swartz K J, Finn S F, Mazurek M F, Kowall N W

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Glutamates; Neuropeptides; Neurotoxins; Neurotransmitter Agents; Quinolinic Acids; Homocysteine; homocysteic acid; Ibotenic Acid; Aspartic Acid; Glutamic Acid; gamma-Aminobutyric Acid; N-Methylaspartate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; NADPH Dehydrogenase; Quinolinic Acid; Kainic Acid;

Mesh terms: Animals; Aspartic Acid/metabolism; Cerebral Cortex/drug effects; Glutamates/metabolism; Glutamic Acid; Homocysteine/analogs & derivatives; Ibotenic Acid/analogs & derivatives; Kainic Acid/toxicity; Male; N-Methylaspartate/toxicity; NADPH Dehydrogenase/metabolism; Neuropeptides/metabolism; Neurotoxins/toxicity; Neurotransmitter Agents/metabolism; Quinolinic Acid; Quinolinic Acids/toxicity; Rats; Rats, Inbred Strains; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; gamma-Aminobutyric Acid/metabolism;

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