Sandrine Bertrand receives a grant from ARLSA

Sandrine Bertrand, director of INCIA and CNRS researcher in the MotoPSyn team, has been awarded a grant of €60,000 by the Association for Research on ALS (ARSLA) for her project “Role of spinal neurons in contact with cerebrospinal fluid in ALS.”

Description of the project

This project aims to investigate the role of cerebrospinal fluid-contacting neurons (CSF-cNs) located around the central canal (CC) of the spinal cord in the pathogenesis of amyotrophic lateral sclerosis (ALS). In neurodegenerative diseases such as ALS, disruptions in cerebrospinal fluid composition and ependymal cell function have been observed, yet the mechanisms driving these changes are poorly understood. In addition to their sensory role, CSF-cNs have recently been shown to possess secretory functions and to release immune-related compounds in response to infection, as well as to control glial scar formation following spinal cord injury. These data indicate a significant role of CSF-cNs in pathological conditions. Our preliminary data suggest that both the ependymal area of the spinal cord and CSF-cNs undergo significant structural and genomic alterations during ALS progression. Our project aims at determining whether CSF-cNs contribute to ALS development using the SOD1^G93A ALS mouse model, while also assessing anatomical changes in the ependymal region of both mice and ALS patients. The two main objectives of the CentralCanALS project are: (1) to characterize anatomical, biochemical, and genomic changes in CSF-cNs and surrounding cells during ALS in mice and histological alteration in the ependymal area of ALS patients; (2) to assess how partial loss of sensory function in CSF-cNs impacts ALS symptoms and survival in mice and (3) to investigate the role of PKD2L1 in immune and inflammatory processes involving CSF-cNs in mice.

By combining advanced mouse models and behavioral analysis with cutting-edge techniques (such as transcriptomics, proteomics, and cell sorting) and post-mortem human tissue analysis, this project aims to uncover the role of CSF-cNS and associated cells in the ependymal area during ALS progression, with the potential to pave the way for innovative diagnostic and therapeutic strategies.