IN VITRO MICROFLUIDIC DESIGN TO STUDY MITOCHONDRIA-MICROTUBULES INTERACTIONS AFTER AN AXONAL TRAUMATIC INJURY
Résumé
A lesion in the nervous system induces cellular and molecular mechanisms leading to irreversible dysfunctions. Post-injured
environment is non permissive for axonal regeneration and CNS neurons also exhibit a reduced intrinsic growth capacity.
Nevertheless, neuronal plasticity is still possible: injured axons can degenerate or regenerate, but mechanisms governing this
response remains elusive. My aim is to understand the relation between microtubules and mitochondria on axon fate after a
traumatic injury, in particular by focusing on the corticospinal tract connecting to the spinal cord neurons. Corticospinal
neurons are known to show poor regeneration capacities after a spinal cord injury. Axonal degeneration is associated with a
fast decrease of NAD+ leading to energy drop, cytoskeletal disorganization and finally axonal degradation. Mitochondria
repositioning in the axon can stimulate regeneration and branching by rescuing energy deficits. In addition, microtubules (MT)
to which converge extracellular cues for intracellular trafficking are also involved in mitochondrial transport. Thereby,
mitochondria and MT are essential in determining the axon fate. I am developping an in vitro set-up with microfluidics oriented
networks of cortico-spinal neurons on which a physical injruy can be apply. This system will allow to study the influence of
post-translationnal MT modifications on mitochondria dynamic during axonal regeneration or degeneration.