Mechanotransduction of neurons: a future strategy for the regeneration of spinal cord lesions?
Funded in: 2017, 2018, 2019, 2020
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Problem: Axons in the spinal cord fail to regenerate
Target: Regenerative pathways in neurons activated by mechanical force
Goal: More and better axon regeneration after SCI
As the body of humans or large animals grows, the distance between the neuron soma and its cellular target increases, resulting the axon to be in a condition of stretching. In 1941 Paul Weiss first postulated that the tensile force from stretching could be a signal that causes the axon to increase in length. Nowadays, it is largely recognized that mechanical force is sufficient to initiate a neurite de novo, to induce axonal growth and to induce axon regeneration. Axonal growth mediated by mechanical tension is perhaps the most remarkable mechanism for axonal elongation described so far and axons have been described to elongate at 1 cm/day (a rate 10 times faster than spontaneous regeneration).
Surprisingly, little or nothing is known about the molecular pathways evoked by the mechanical force and no practical applications have been proposed so far. The project aims to gain insights on these molecular mechanisms and to translate them in a strategy to induce the regeneration of spinal cord lesions. In order to stretch axons we will take advantage of magnetic micropost technology, which is able to apply small mechanical forces with precision and accuracy. The study will be performed on an in vitro model of nerve regeneration, which recapitulates the biochemical events occurring during nerve regeneration of neurons from the central nervous system (a spinal cord slice) towards the periphery (a sciatic nerve). The molecular pathway(s) activated by mechanical force will be studied by using high throughput sequencing techniques. The expected results is to validate a unified model of axonal growth and, most importantly, to discover completely new therapeutic targets. The potential application is to allow the neurosurgeons of the future to remotely manipulated, guide and enhance axon regeneration, addressing the dream of the re-innervation of the desired target after injury or disease.