The TrkB signalling at the neuromuscular junction of amyotrophic lateral sclerosis mice. The protective effect of exercise.

Identificador:  TDX:4010

Handle: https://hdl.handle.net/20.500.11797/TDX4010

Autores:  Just Borràs, Laia

Resumen:
The bidirectional communication between the synaptic and the neurotrophic control at the neuromuscular junction (NMJ) promote its well function and the maintenance of the cell partners, including motor neurons, myocytes and glial cells. Thus, neurodegenerative diseases that induce the NMJ dismantling, such as Amyotrophic lateral sclerosis (ALS), could be related with the loss of this bidirectional relation. The neurotrophic control is partially mediated by myokines with neurotrophic capacity, such as BDNF or NT-4. They trigger presynaptic signalling pathways through the retrograde activation of TrkB receptor, that, at its turn, modulate kinases like PKC and PKA to phosphorylate exocytotic machinery proteins and consequently, regulates neurotransmission. Thus, presynaptic activity and the resulting muscle contraction are affected by the TrkB signalling pathway in a feedback loop to preserve NMJ function under physiological conditions. Consequently, changes in the TrkB signalling modify the NMJ balance, resulting in either neuromuscular dysfunction or reinforcement. Therefore, the aim of the present thesis is to understand how the changes at the NMJ influence the TrkB signalling pathway, in correlation with decreased neuroprotective capacity, like in ALS. Furthermore, the aim is also to determine the capacity of physical exercise to recover or improve the signalling and its neuroprotective capacity under different conditions.