L-Cysteine

Abstract NMDA receptors). Therefore, hypoxic/ischemic (H/I) brain damage in infant rodents may be mediated exclusively by interaction of endogenous Glu with NMDA receptors (1,4). Cys preferentially destroys neuronal populations that are also most sensitive to H/I injury (18) and the NMDA antagonist, MK-801, prevents either Cys-induced (2,8) or H/I (3,7) damage in infant rat brain. Moreover, it appears that within a several-week period, during which the postnatal rodent brain is hypersensitive to NMDA neurotoxicity, each of the vulnerable neuronal populations may be governed by its own timetable for reaching peak sensitivity (1). L-Cysteine (Cys) is a common sulfur-containing amino acid which, like glutamate, is found ubiquitously in nature, is a normal constituent of foods, and is present in the human body and CNS. Cys administered orally or subcutaneously can damage many regions of the fetal or infant forebrain in pregnant rodents or their neonatal offspring (6). Cys neurotoxicity has been shown to be a form of excitotoxicity mediated by N-methyl-D-apartate (NMDA) receptors (and prevented by NMDA receptor antagonists) (2,8). Cys neurotoxicity is augmented by bicarbonate (i.e., in the presence of physiological concentrations of bicarbonate, Cys is transformed from a relatively weak to a more potent excitotoxin). This may stem from the ability of bicarbonate to facilitate the conversion of Cys to an a-amino carbamate molecule that stereochemically resembles the potent excitotoxin, NMDA (5). Cys appears to be a unique excitotoxin that can penetrate both placental and blood-brain barriers and, after entering the brain, may undergo conversion to a molecule that potently interacts with NMDA receptors to destroy neurons in the immature forebrain. Cys has also been proposed to act synergistically with glutamate to produce neurotoxicity in immature rat arcuate nucleus in vivo (9). Cys-induced tonic seizures in mice are attenuated by N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthase (10).