Stereospecificity of the gliotoxic and anti-neurotoxic actions of alpha-aminoadipate.

The glutamate (Glu) analog, DL-alpha-aminoadipate (DL-alpha AA), and the separate D and L isomers of alpha AA, were administered subcutaneously to infant mice and histopathological effects on the arcuate hypothalamic (AH) nucleus were studied. L-alpha AA induced striking gliotoxic and neurotoxic changes; D-alpha AA and DL-alpha AA respectively induced mild and extreme gliotoxic but not neurotoxic changes. The neurotoxicity of L-alpha AA is of interest in view of its known neuroexcitatory potential. The non-neurotoxicity of DL-alpha AA implies effective antagonism by D-alpha AA of the neurotoxicity of L-alpha AA, which is of interest in that D-alpha AA is recognized as an effective antagonist of amino acid excitants and is thought to block specifically at the excitatory receptor.