Ontogeny and localization of the neutral amino acid transporter ASCT1 in rat brain

Abstract

ASCT1 is a protein that encodes System ASC, a sodium-dependent amino acid transport activity that transports primarily zwitterionic amino acids at physiological pH. ASCT1 has a 39–44% identity to the EAAT family of glutamate transporters. At extracellular pH values below 7.4, ASCT1 shifts substrate specificity to transport anionic amino acids. In this study we have examined the location of the ASCT1 transporter by immunohistochemistry in the developing rat brain. In addition, we have examined the cellular localization of ASCT1 in glial and neuronal cultures. The presence of ASCT1 immunoreactivity (ASCT1ir) in the developing brain was detectable as early as 14 days of gestation. At the cellular level, ASCT1ir was prominent in hippocampal pyramidal and dentate granule neurons. In the cerebellum, Purkinje cells and their dendrites were intensely labeled, whereas the granule and molecular layers were moderately labeled. In the cerebral cortex, neuronal cell bodies in all lamina and scattered astrocytes showed intense ASCT1ir. Double labeling experiments in vitro confirmed that ASCT1 was localized to both glia and neurons. These data illustrate that the rat ASCT1 transporter is expressed in the developing brain at levels equivalent to those observed in adult tissue. In addition, the expression and localization of ASCT1 are consistent with its possible role in pathophysiological processes that involve glutamate toxicity.