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DL- and L-alpha-aminoadipic acid (alpha-AA) are specific gliotoxins in vitro (Huck, S., F. Grass, and M. E. Hatten (1984) Neuroscience 12: 783-796). By combining immunohistochemical and autoradiographic techniques, we now show that DL-[14C]-alpha-AA is accumulated almost selectively by astrocytes in cultures of the dissociated postnatal mouse cerebellum, presumptive neurons being free of the radiolabel. High pressure liquid chromatography analysis of cultures incubated with D- or L-alpha-AA and DL-[14C]-alpha-AA autoradiograms conducted in the presence of D- or L-alpha-AA reveal a stereospecificity of astroglial L-alpha-AA uptake. Both the uptake of alpha-AA by astrocytes and alpha-AA-induced gliotoxicity were sodium dependent. Since 2 microM tetrodotoxin did not prevent the morphological changes, we conclude that sodium plays its role in alpha-AA-induced gliotoxicity by mediating the transport of the substance. Thus, alpha-AA appears to be taken up by the astrocytes before exerting its cytotoxic effect.

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