Ontogeny of glutamate transporters in the sheep brain

Extracellular glutamate can he neurotrophic or neurotoxic in the developing brain, depending on the concentration which is regulated by glutamate transporter proteins. Using immunoblotting and immunocytochemistry (ICC), we tested the hypothesis that expression of neuronal (EAAC1) and glial (GLT) glutamate transporter proteins was regionally and temporally regulated in the developing brain. Immunoblots for EAAC1 revealed a single immunere active (IR) band at 7OkDa. whereas 73 and 140kl)a proteins were seen with GLT antibodies. EAAC1 and GLT are regulated differently during development with EAAC1 being most abundant at (i() days (d) completed gestation (term=145d} and dissipating thereafter while GLT was most abundant ,at 13Bd gestation. ICC confirmed these observations and revealed that GLT is expressed by neuronal and nonneuronal cell types during mid gestation with astrocyte IR first evident at 93d and glial selectivity developing by!36d. During midgestation transient expression of GLT is seen in pyramidal cells in hippocampus, motor neurons in cranial nerve nuclei, subplate neurons, and Purkinje cells in the cerebellum. Conversely, EAAC1 expression is predominantly neuronal throughout gestation with intense labeling of dendrites within the telencephulon evident at GOd. Neuropü. neuronal cell bodies and processes are EAAC1+ throughout gestation with no evidence of astrocytic or oligodendroglial IR. The differential and developmental regulation of these protrins may have implications for our understanding of changes in cellular vulnerability to hypoxic/ ischémie and traumatic events during development.