Cellular and subcellular distribution of D-aspartate oxidase in human and rat brain

The unusual amino acid D-aspartate is present in significant amounts in brain and endocrine glands and is supposed to be involved in neurotransmission and neurosecretion (Wolosker et al. [2000] Neuroscience 100:183-189). D-aspartate oxidase is the only enzyme known to metabolize D-aspartate and could regulate its level in different regions of the brain. We examined the cellular and subcellular distribution of this enzyme and its mRNA in human and rat brain by immunohistochemistry, in situ hybridization, and immunoelectron microscopy. D-aspartate oxidase protein and mRNA are ubiquitous. The protein shows a granular pattern, particularly within neurons and to a significantly lesser extent in astrocytes and oligodendrocytes. No evidence for a synaptic association was observed. Whereas between most positive neurons only gradual differences were observed, in the hypothalamic paraventricular nucleus, neurons with high enzyme content were found next to others with no labeling. cDNA cloning of D-aspartate oxidase corroborates an inherent targeting signal sequence for protein import into peroxisomes. Immunoelectron microscopy showed that the protein is localized in single membrane-bound organelles, apparently peroxisomes.