Developmental regulation of glutamate transporters and glutamine synthetase activity in astrocyte cultures differentiated in vitro

Glutamate plays an important role in brain development; physiological funct ion, and neurodegeneration. Astrocytes control synaptic concentration of gl utamate via the high affinity glutamate transporters, GLT-1 and GLAST, and the glutamate catabolizing enzyme, glutamine synthetase. In this study we s how that astrocytes cultured from rat brain in various; stages of developme nt including embryonic (E18), postnatal (P1-P21) and mature (P50), show dis tinct patterns of GLT-1 and GLAST expression, glutamine synthetase activity , and phenotypic changes induced by dibutyryl-cyclic adenosine monophosphat e. The transcripts for GLT-1 message were detectable in embryonic astrocyte s only, whereas the GLAST message was highly expressed in E1S and P1-P4 ast rocyte cultures, declined in P10-P21, and was undetectable in P50 astrocyte s. Uptake of H-3-glutamate correlated well with GLAST expression in astrocy te cultures of all developmental stages. Glutamine synthetase activity sign ificantly declined from high embryonic levels in P4 astrocytes and remained low throughout postnatal maturation. Exposure of astrocyte cultures to the differentiating agent, db-cAMP (250-500 mu M; 6 days), resulted in a prono unced stellation, up regulation of GLT-1 and GLAST in E18, and GLAST in P4 cultures, while it was ineffective in P10 astrocytes. By contrast, db-cAMP induced a more pronounced stimulation of glutamine synthetase activity (up to 10-fold above basal) in P10 than in E18 cultures(up to 2 times above bas al). The differences in expression/inducibility of glutamate transporters a nd glutamine synthetase observed in astrocyte cultures derived from various stages of fetal and postnatal development suggest that astrocytes in vivo might also respond differently to environmental or injurious stimuli during development and maturation. (C) 1999 ISDN. Published by Elsevier Science L td. All rights reserved.