Dopamine cross-reacts with adrenoreceptors in cortical astrocytes to induce BDNF expression, CREB signaling and morphological transformation.

Abstract

Expression of brain-derived neurotrophic factor (BDNF) is induced in cultured rat cortical astrocytes by catecholamines norepinephrine and dopamine as well as selective α1 and β adrenergic agonists. However, it has remained unknown which receptors mediate dopamine-induced BDNF upregulation in astrocytes. Here, we demonstrate that β adrenoreceptors are the main mediators of this effect in cultured cortical astrocytes, while α1 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 CREB-mediated 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 β adrenoreceptors.