Mechanism of GABA(B) receptor-induced BDNF secretion and promotion of GABA(A) receptor membrane expression.

Kuczewski, N., Fuchs, C., Ferrand, N., Jovanovic, J.N., Gaiarsa, J-L. and Porcher, C. (2011) Mechanism of GABA(B) receptor-induced BDNF secretion and promotion of GABA(A) receptor membrane expression. Journal of Neurochemistry . 10.1111/j.1471-4159.2011.07192.x.

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DOI: 10.1111/j.1471-4159.2011.07192.x

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, CREB, 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-TrkB dependent signalling pathway.

Item Type:Article
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:2006
Journal or Publication Title:Journal of Neurochemistry
Deposited By:Library Staff
Deposited On:01 Apr 2011 15:03
Last Modified:01 Apr 2011 16:41

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