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Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system

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The brains and retinas of infant mice were examined following subcutaneous administration of monosodium glutamate (MSG) and structurally related compounds in an attempt to clarify the molecular specificity of MSG-induced neuropathology. Based on the effects on the infant retina and hypothalamus all compounds could be placed into one of four groups: 1. Those equipotent with L-MSG in necrosing neurons. 2. Those substantially more potent than L-MSG in necrosing neurons. 3. Those which affect non-neuronal components (glial, ependymal, Muller cells) without appreciable effects on neurons. 4. Those with no cytotoxic effects. Except for L-cysteine, all neurotoxic compounds were acidic amino acids known to excite neurones, the most potent neurotoxic compounds being those which are powerful neuroexcitants (N-methyl DL-aspartic and DL-homocysteic acids). The exception posed by L-cysteine may be more apparent than real in that the in vivo conversion of the SH terminal to a more acidic group (SO2H or SO3H) could account for its neurotoxicity. The close correspondence in molecular specificities associated with neurotoxic and neuroexcitatory properties of simple amino acids suggests the two phenomena may be governed by similar mechanisms of action.

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Supported in part by PHS grants MH 38894 (Research Career Development Award to John W. OIney) and NS 09156. We thank Dr. E. Robins for suggestions in preparation of the manuscript.

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Olney, J.W., Ho, O.L. & Rhee, V. Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system. Exp Brain Res 14, 61–76 (1971).

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