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 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.

Effects of Monoamines and Antidepressants on Astrocyte Physiology: Implications for Monoamine Hypothesis of Depression

“…It is shown that dopamine as well as norepinephrine induces BDNF expression in cultured astrocytes. 59 The effects of dopamine are brought about by its cross-reactivity with norepinephrine receptors. 59 Hence, astrocytic norepinephrine receptors may cell autonomously induce BDNF secretion in response to norepinephrine-enhancing antidepressant drugs.…”

“… 59 The effects of dopamine are brought about by its cross-reactivity with norepinephrine receptors. 59 Hence, astrocytic norepinephrine receptors may cell autonomously induce BDNF secretion in response to norepinephrine-enhancing antidepressant drugs. Such mechanisms need more thorough investigation as they may lie at the heart of mechanism of action of antidepressant drugs.…”

“…One study found that the BDNF induction by norepinephrine or dopamine is brought about by β-noradrenergic receptors, whereas the α 1 receptors contribute to a much lesser extent 59 ; another study found that β as well as α 1 -noradrenergic receptors contributes to norepinephrine-mediated BDNF induction. 60 Moreover, activation of adenylate cyclase, protein kinase A (PKA) or protein kinase C (PKC) could mimic BDNF increase.…”

α-Synuclein and Noradrenergic Modulation of Immune Cells in Parkinson’s Disease Pathogenesis

“…NE can also enhance BDNF transcription and BDNF/TrkB kinetics ( Chen et al, 2007 ). Activation of the β1-adrenergic receptor stimulates BDNF transcription in astrocytes ( Koppel et al, 2018 ). When BDNF binds to TrkB, signal transduction is mediated by TrkB dimerizing and autophosphorylating ( Haniu et al, 1997 ).…”

Vascular endothelial growth factor increases the function of calcium‐impermeable AMPA receptor GluA2 subunit in astrocytes via activation of protein kinase C signaling pathway

“…As we have well known, astrocytes can secrete several neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) (Koppel et al, 2018), fibroblast growth factor (FGF) (Kajitani et al, 2015;Zhang et al, 2009), and vascular endothelial growth factor (VEGF) (Ijichi, Sakuma, & Tofilon, 1995). It has been reported that BDNF and FGF can modulate neurogenesis (Kang & Hebert, 2015), brain development (Marte, Messa, Benfenati, & Onofri, 2017;Shimada, Yoshida, & Yamagata, 2016).…”