In vitro Modelling of Human Healthy and ALS Proprioceptive Sensory Neurons in the Neuromuscular System
45 Pages Posted: 12 Jan 2022 Publication Status: Review Complete
More...Abstract
Proprioceptive sensory neurons (pSN) are an essential and undervalued part of the neuromuscular circuit. A developed protocol to differentiate healthy and amyotrophic lateral sclerosis (ALS) human neural stem cells (hNSC) into pSN, and their comparison with the motor neuron (MN) differentiation process from the same hNSC sources, facilitated the development of in-vitro coculture platforms. The obtained pSN spheroids cultured with human skeletal myocytes recreated afferent neuromuscular connections, in which we observed the formation of annulospiral wrappinglike structures between TrkC+ neurons and a multinucleated muscle fiber, presenting synaptic bouton-like structures in the contact point. The genetic profile comparative analysis performed in healthy and ALS hNSC differentiated to pSN showed that basal levels of ETV1, critical for motor feedback from pSN, were much lower for ALS samples and that the pSN genetic profile varies between healthy and ALS samples, suggesting a strong involvement of pSN in ALS pathology development and progression.
Keywords: neuromuscular systems, sensory neurons, ALS, In vitro 3D neuromuscular models
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