期刊
JOURNAL OF NEUROCHEMISTRY
卷 118, 期 4, 页码 533-545出版社
WILEY
DOI: 10.1111/j.1471-4159.2011.07192.x
关键词
activity; BDNF; CREB; development; GABA; GABA(B); neurotrophin
资金
- INSERM
- CNRS
- ANR (French national research council)
- FRM (Fondation pour la Recherche Medicale)
- ANR
- LFCE (Ligue Francaise Contre l'Epilepsie)
- MRC, UK
- MRC [G0800498] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/C507237/1] Funding Source: researchfish
- Medical Research Council [G0800498] Funding Source: researchfish
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 Ca2+ channels. We further show that once released by GABAB receptor activation, BDNF increases the membrane expression of beta(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.
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