Expression of brain-derived neurotrophic factor (BDNF) is induced in cultured rat cortical astrocytes by catecholamines norepinephrine and dopamine as well as selective a1 and b adrenergic agonists. However, it has remained unknown which receptors mediate dopamine-induced BDNF upregulation in astrocytes. Here, we demonstrate that b adrenoreceptors are the main mediators of this effect in cultured cortical astrocytes, while a1 adrenoreceptors and D1 dopamine receptors contribute to a lesser extent. We show that in cortical astrocytes BDNF exon IV and exon VI containing mRNAs are induced by dopamine and norepinephrine via CREB-dependent signaling and that this regulation is mediated by a mechanism that is distinct from activity-dependent CREBmediated activation of BDNF transcription in neurons. We also show that regulation of BDNF promoters IV and VI by catecholamines requires a distal regulatory element in the BDNF locus.Finally, we demonstrate that dopamine-induced astrocyte stellation and induction of CREB signaling are mediated by cross-reaction of dopamine with b adrenoreceptors.
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