Effects of Neurotrophic Factors on Neuromuscular Junction Maturation

The neuromuscular junction undergoes a maturation process physiologically after initial nerve-muscle contact, which is characterized by spontaneous synaptic current amplitude increase and rise time decrease, as well as the development of well-defined quantal ACh release. Chronic application of BDNF and elevation of intracellular cAMP resulted in inhibition in the maturation process, while NT-3, NT-4, GDNF, HB-GAM and HGF appeared to promote it. The response to BDNF was mediated by TrkB receptor. PKA inhibitors could reverse the inhibitory effects of cAMP and BDNF, which suggests that cAMP and BDNF suppress NMJ maturation through cAMP-PKA-dependent signaling pathway. Further investigations revealed that CaMKs and intracellular Ca2+ mediate the inhibitory effects of cAMP and BDNF.