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Mechanism of GABA B receptor‐induced BDNF secretion and promotion of GABA A receptor membrane expression
Author(s) -
Kuczewski Nicola,
Fuchs Celine,
Ferrand Nadine,
Jovanovic Jasmi.,
Gaiarsa JeanLuc,
Porcher Christophe
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07192.x
Subject(s) - tropomyosin receptor kinase b , microbiology and biotechnology , gabaergic , receptor , brain derived neurotrophic factor , biology , gabaa receptor , signal transduction , chemistry , neurotrophic factors , medicine , endocrinology , biochemistry
J. Neurochem. (2011) 118 , 533–545. Abstract Recent studies have shown that GABA B receptors play more than a classical inhibitory role and can function as an important synaptic maturation signal early in life. In a previous study, we reported that GABA B receptor activation triggers secretion of brain‐derived neurotrophic factor (BDNF) and promotes the functional maturation of GABAergic synapses in the developing rat hippocampus. To identify the signalling pathway linking GABA B receptor activation to BDNF secretion in these cells, we have now used the phosphorylated form of the cAMP response element‐binding protein as a biological sensor for endogenous BDNF release. In the present study, we show that GABA B receptor‐induced secretion of BDNF relies on the activation of phospholipase C, followed by the formation of diacylglycerol, activation of protein kinase C, and the opening of L‐type voltage‐dependent Ca 2+ channels. We further show that once released by GABA B receptor activation, BDNF increases the membrane expression of β 2/3 ‐containing GABA A receptors in neuronal cultures. These results reveal a novel function of GABA B receptors in regulating the expression of GABA A receptor through BDNF‐tropomyosin‐related kinase B receptor dependent signalling pathway.