Brain-derived neurotrophic factor inhibits neuromuscular junction maturation in a cAMP-PKA-dependent way

Brain‐derived neurotrophic factor inhibits neuromuscular junction maturation mediated by inTracellular Ca2+ and Ca2+/calmodulin‐dependent kinase

“…24 In mesenchymal stem cells (MSCs) derived from the adult bone marrow, BDNF treatment also increased intracellular Ca 21 levels and promoted functional maturation. 25 In the Xenopus nerve-muscle coculture system, our own recent studies showed that BDNF treatment upregulated presynaptic cAMP-PKA signaling, 4 which had negative effects on NMJ maturation. 3 In addition, elevation of cytosolic Ca 21 signaling was required for cAMP-PKA signaling to regulate synaptic maturation.…”

“…Xenopus nerve-muscle cocultures were prepared as described previously. 4 In brief, neural tube and myotomal tissues were dissected from Xenopus embryos at stages [20][21][22] (FBS), and 2% antibiotics, composed of 100 units/ml penicillin, 100 lg/ml gentamicin, and 100 lg/ml streptomycin. The cultures were kept for 1-3 days before use.…”

“…The micropipette solution consisted of 150 mM KCl, 1 mM NaCl, 1 mM MgCl 2 , 10 mM HEPES, pH 7.2). 4 The membrane potential of the muscle cell was voltage-clamped at -70 mV. The signals were collected by an amplifier (Axopatch 200B; Molecular Devices, Inc., Sunnyvale, California) and sampled at 10 kHZwith the filter set at 2 kHZ.…”

“…As NMJs develop, the ACh packaging within some SVs becomes larger and uniform, leading to a shift of amplitude distribution to a "bell-shaped" histogram centering on larger SSC amplitude. 3,4 Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that acts through TrkB receptor tyrosine kinase. 5 In previous research, this growth factor has shown great nutrient effects on spinal motor neurons.…”

“…However, its long-term biological effects on NMJ maturation were found to be negative in our recent study. 4 Because both BDNF and intracellular Ca 21 signaling are essential for neuronal development, we investigated whether there is crosstalk in the long-term effects of BDNF in NMJ maturation.…”