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Dopamine cross‐reacts with adrenoreceptors in cortical astrocytes to induce BDNF expression, CREB signaling and morphological transformation
Author(s) -
Koppel Indrek,
Jaanson Kaur,
Klasche Airi,
Tuvikene Jürgen,
Tiirik Tõnis,
Pärn Angela,
Timmusk Tõnis
Publication year - 2018
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23238
Subject(s) - creb , dopamine , brain derived neurotrophic factor , neurotrophic factors , astrocyte , biology , medicine , neuroscience , dopamine receptor , endocrinology , downregulation and upregulation , receptor , microbiology and biotechnology , transcription factor , central nervous system , biochemistry , gene
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.