title: Brain-derived neurotrophic factor inhibits neuromuscular junction maturation in a cAMP-PKA-dependent way.
abstract: The development of neuromuscular junction (NMJ) is initiated by motor axon's contact with the skeletal muscle cell that is followed by synaptic maturation. Previous studies showed that brain-derived neurotrophic factor (BDNF) enhanced motoneurons' survival and growth but significantly inhibited synaptogenesis. Here, we report that chronic application of BDNF resulted in inhibition in the maturation process both physiologically and morphologically. The response to BDNF was mediated by its cognate receptor TrkB as the effects were abolished by Trk receptor inhibitor K252a. Protein kinase A (PKA) inhibitor reversed the effects of BDNF in inhibiting NMJ maturation. These results indicate that BDNF suppresses NMJ maturation through cAMP-PKA signaling pathway. Together with the previous studies, these results suggest that BDNF suppresses NMJ formation and maturation despite its effects in enhancing neuronal survival and growth.
authors: Peking University Health Science Center, Beijing 100191, China; Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: sw@hsc.pku.edu.cn.
authors: Wei
authors: W
authors: Song
authors: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: albertxiwanjin@gmail.com.
authors: Xiwan Albert
authors: XA
authors: Jin
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D026121:Indole Alkaloids / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D020813:Receptor, trkB / Q000037:antagonists & inhibitors; D014981:Xenopus
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D026121:Indole Alkaloids; C049985:staurosporine aglycone; D000242:Cyclic AMP; D020813:Receptor, trkB; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Brain-derived neurotrophic factor; Cyclic AMP; Protein kinase A; Synaptic maturation; TrkB receptor