The Neurodegenerative Properties Of Intracerebral Quinolinic Acid And Its Structural Analog Cis-2,3-Piperidine Dicarboxylic Acid

Abstract

Experiments using intracerebral injections in rodents of kainic (KA) or ibotenic (IBO) acid, two amino acids of plant and fungal origin, respectively, have led to the hypothesis that human neurodegenerative diseases, e.g. Huntington’s disease (HD) and temporal lobe epilepsy, may be related to a pathological overproduction of endogenous neuroexcitatory amino acids (Coyle et al., 1977; Divac, 1977; Olney and de Gubareff, 1978; French et al., 1982). Of these, glutamate, aspartate and cysteine sulfinate, all putative neurotransmitters in the central nervous system (Roberts et al., 1981; Recasens et al., 1982), do not appear to posses pronounced neurotoxicity, even when introduced into the brain at very high concentrations (Olney and de Gubareff, 1978; Mangano and Schwarcz, 1983). Also, examinations of acidic amino acids in tissues and body fluids of patients suffering from HD or epilepsy have merely yielded equivocal results (Perry et al., 1975; Gray et al., 1980; Perry and Hansen, 1981; Mangano and Schwarcz, 1981, 1982). Their dysfunction in neuro-psychiatric disorders has as yet not been established.