DISTRIBUTION OF GLUTAMATE TRANSPORTER SUBTYPES DURING HUMAN BRAIN-DEVELOPMENT

In the mature brain, removal of glutamate from the synaptic cleft play s an important role in the maintenance of subtoxic levels of glutamate . This requirement is handled by a family of glutamate transporters, E AAT1, EAAT2, EAAT3, and EAAT4. Due to the involvement of glutamate als o in neuronal development, it is believed that glutamate transport pla ys a role in developmental processes as well. Therefore, we have used immunohistochemical and immunoblot analysis to determine the distribut ion of the four glutamate transporters during human brain development using human pre-and postnatal brain tissue. Regional analysis showed t hat each transporter subtype has a unique distribution during developm ent. EAAT2 was the most prominent glutamate transporter subtype and wa s highly enriched in cortex, basal ganglia, cerebellum, and thalamus i n ail ages examined. EAAT1 immunoreactivity was lower than that of EAA T2, with predominant localization in cortex, basal ganglia, hippocampu s, and periventricular region. EAAT3 was located mainly in cortex, bas al ganglia, and hippocampus, and EAAT4 was found only in cortex, hippo campus, and cerebellar cortex. The distinct regional distribution of v arious EAAT subtypes and also the transient expression of specific EAA T subtypes during development suggest multiple functional roles for gl utamate transporters in the developing brain.