30 Septembre 2022 – Valeria Cavalli – Satellite Glial Cells in sensory nervous system health, injury and disease

Exceptionnellement ce séminaire aura lieu en Salle des thèses (3ème étage) – Campus Saint-Germain-des-Prés, 45 rue des Saints-Pères, 75006 Paris

Research in my laboratory focuses on elucidating the principles and mechanisms by which peripheral nervous system neurons regenerate, and to identify therapeutic targets to improve neuronal recovery following axon injury.

To understand why regeneration occurs in the peripheral but not the central nervous system, our lab studies a unique cell type that spans both systems: sensory neurons of the dorsal root ganglia. The cell bodies of sensory neurons are located in the dorsal root ganglion, a structure that sits just outside the spinal cord. These sensory neurons have a unique pseudo-unipolar morphology with a single axon which bifurcates within the ganglion; one axon proceeds along peripheral nerves and the other proceeds centrally along the dorsal root into the spinal cord. Importantly, the peripheral axon has a much greater regenerative capacity than the central axon. Using this system, we have discovered epigenetic, transcriptional and translational pathways employed by peripheral neurons to increase their growth capacity.

While we continue to study the signaling pathways elicited in sensory neurons, we recently turned our attention to the possibility that other cells residing in dorsal root ganglia contribute to the nerve repair process. We focused on the glial cells that envelop the sensory neuron soma, known as satellite glial cells (SGC). Our discovery that SGC contribute to nerve repair significantly shifts the research landscape surrounding peripheral nerve injury to include consideration of sensory neuron microenvironment in nerve injury. Specifically, we discovered that PPARa activity downstream of fatty acid synthase (Fasn) in SGC represents a novel mechanism mediating axon regeneration in adult peripheral nerves. This response fails after spinal cord injury and may contribute to the poor pro-regenerative response of sensory neurons after central nervous system injury. Notably, we found that treatment with the FDA-approved PPARα agonist fenofibrate increased axon regeneration after dorsal root injury. Importantly, we also found that that key features of SGC in rodent model, including lipid metabolism and similarities between SGC and astrocytes are conserved in human SGC. We also found that other cell types, including macrophages, endothelial cells, and mesenchymal cells respond differently to peripheral vs central injuries. Our studies point to the importance of better understanding the contribution of other DRG resident cells in nerve injury responses, which may pave the way for improved efficiency in translating discovery into new treatments of nerve injury.