ИСТИНА

Aims: Recently we have shown that stimulation of postsynaptic PAR1 thrombin receptors suggested the release of BDNF as a retrograde signal. The particular signaling pathways triggered by BDNF followed by changes in synaptic transmission in mouse motor synapses have been investigated poorly. Methods: The mechanisms underlying the BDNF-induced modulation of acetylcholine release were studied using intracellular microelectrode recordings of miniature endplate potentials (MEPPs) and multiquantal endplate potentials (EPPs) in mouse diaphragm neuromuscular preparations. Results: BDNF (1 nM) increased both the MEPP frequency and amplitude. Phospholipase C mediates the increase only in MEPP frequency. The increase in MEPP amplitude was due to the quantal size enhancement since this effect was prevented by vesamicol or bafilomycine A1. BDNF-induced increase in quantal size, but not in MEPP frequency was fully prevented by blocking MEK/Erk-pathway with U0126 or by inhibition of PKA with H-89. The activity of adenosine A2A-receptors is required for the manifestation of BDNF effect on MEPP amplitude: A2A-blocker ZM241385 greatly diminished the BDNF effect on MEPP amplitude. On the contrary, prolonged stimulation of A2A-receptors with CGS21680 increased the amplitude of MEPPs by itself and occluded the BDNF effect. BDNF increased EPP amplitude in short trains (50 Hz, 1 s) mainly due to the increase in the quantal size since the EPP quantal content was increased only at the beginning of EPP train. Conclusion: Our data suggest that BDNF simultaneously triggers multiple presynaptic signaling pathways leading to upregulation of acetylcholine release in motor synapses. The work was supported by RFBR grant 19-04-00616a.