D-aspartate localizations imply neuronal and neuroendocrine roles

Though L-amino acids predominate in living organisms, substantial levels of free D-serine and D-aspartate occur in mammals, especially in nervous and endocrine tissues. Using an antibody specific for glutaraldehyde-fixed D-aspartate, we have localized D-aspartate in rat tissues. In the brain we observe discrete neuronal localizations of D-aspartate, especially in the external plexiform layer of the olfactory bulb, hypothalamic supraoptic and paraventricular nuclei, the medial habenula, and certain brainstem nuclei. In rats 3-4 weeks old, we observe D-aspartate in septal nuclei and in a subset of stellate and basket cells of the cerebellum. D-aspartate is also concentrated in glands, including the epinephrine cells of the adrenal medulla, the posterior pituitary, and the pineal gland. Levels in the pineal gland are the highest of any mammalian tissue. D-aspartate oxidase, visualized by enzyme histochemistry, is concentrated in neurons of the hippocampus, cerebral cortex, and olfactory epithelium, as well as choroid plexus and ependyma. Localizations of D-aspartate oxidase are reciprocal to D-aspartate, suggesting that the enzyme depletes endogenous stores of the amino acid and might inactivate synaptically released D-aspartate.