Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ.

Laia Just-Borràs,Víctor Cilleros-Mañé,Olivier Biondi,Maria A Lanuza,Erica Hurtado,Marta Tomàs,Josep Tomàs,Frédéric Charbonnier,Neus Garcia

doi:10.3390/ijms22094577

Laia Just-Borràs, Víctor Cilleros-Mañé + Show 7 more

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https://doi.org/10.3390/ijms22094577

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Abstract

Physical exercise improves motor control and related cognitive abilities and reinforces neuroprotective mechanisms in the nervous system. As peripheral nerves interact with skeletal muscles at the neuromuscular junction, modifications of this bidirectional communication by physical activity are positive to preserve this synapse as it increases quantal content and resistance to fatigue, acetylcholine receptors expansion, and myocytes’ fast-to-slow functional transition. Here, we provide the intermediate step between physical activity and functional and morphological changes by analyzing the molecular adaptations in the skeletal muscle of the full BDNF/TrkB downstream signaling pathway, directly involved in acetylcholine release and synapse maintenance. After 45 days of training at different intensities, the BDNF/TrkB molecular phenotype of trained muscles from male B6SJLF1/J mice undergo a fast-to-slow transition without affecting motor neuron size. We provide further knowledge to understand how exercise induces muscle molecular adaptations towards a slower phenotype, resistant to prolonged trains of stimulation or activity that can be useful as therapeutic tools.

Highlights

Motor neurons (MNs) interact with skeletal muscles through the neuromuscular junction (NMJ) to regulate themselves in a feedback loop mode [1,2,3]
We have recently found that the Brain-derived neurotrophic (BDNF)/Tropomyosin receptor kinase B (TrkB) signaling pathway, including kinases directly involved in the acetylcholine (ACh) release machinery, are differently expressed in slow and fast muscles
We analyzed total and phosphorylated protein levels of the BDNF/TrkB downstream signaling pathway including BDNF and NT4 neurotrophic factor (NTF); their receptors TrkB and p75 neurotrophic factor receptor (p75NTR); three downstream protein kinases C (PKC) (α, βI and ε) and its priming kinase (PDK1); the different protein kinase A (PKA) subunits; and two PKC and PKA targets related with neurotransmitter release (Munc18-1 and synaptosomal nerve-associated protein 25 (SNAP-25))

Summary

Introduction

Motor neurons (MNs) interact with skeletal muscles through the neuromuscular junction (NMJ) to regulate themselves in a feedback loop mode [1,2,3]. Exercise is beneficial for the nervous system [7] as it improves motor control and cognitive abilities and reinforces neuroprotective mechanisms in brain [8], spinal cord [9,10], peripheral nerves, and muscles [11]. Among others, it induces cellular adaptations [12,13], increases mitochondrial capacity [14], and raises neurotrophic factor (NTF) expression [9]

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