Learning by Research

Thesis Title: Axon guidance modalities in the context of adult central nervous system regeneration

The central nervous system (CNS), consisting of the brain, the spinal cord and the optic and olfactory nerves can undergo different affections: traumatic (spinal cord or brain traumatisms) or degenerative diseases (Alzheimer’s disease, Parkinson’s disease, glaucoma). These affections that destroy neuronal circuits induce irreversible loss of cognitive, sensitive and/or motor functions. Until now, these lesions have permanent consequences because the CNS is not able to regenerate after an injury. Moreover, there is no treatment available currently.
But today, long distance regeneration (from the eye to the brain) is possible thanks to neurons modulation. Unfortunately, this regrowth does not lead to a return of functions. Indeed, regrowing neurons are lost on their path and do not reconnect their correct targets: they need to be guided. Axon guidance is a process occurring during embryonic development allowing axons (neurons extension) to be brought to their target in the body.

First, I highlighted the presence of guidance signaling in the adult brain. Then, I modulated these signals in order to correct the regrowing axons trajectory. Thus, I achieved to bring the regenerating axons back to one of their correct targets. I also showed that the newly formed connection is functional. This study highlighted the importance of guiding the regenerating neurons in order to rebuild new functional circuits. These breakthroughs will be of crucial importance to develop innovative therapies to repair lesioned CNS but also for neurodegenerative diseases.

Key Words: Régénération (biologie), système nerveux central, cellules ganglionnaires de la rétine, rétine, suprachiasmatic nucleus, guidage axonal

Doctoral School: ED CSV – Chemistry and Life Sciences
Research laboratory: Institut des neurosciences de Grenoble (GIN - Inserm/UGA)
Thesis supervision: Marylin VANTARD and Homaira NAWABI

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