Project summary :
Multiple sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system (CNS), characterized by demyelination and chronic inflammation, as well as axonal and neuronal loss, affecting 2 to 3 million people worldwide. , including 115,000 in France. Among the many neurological symptoms of MS, pain is a common disabling symptom, often not alleviated by available medications. Recent data suggest the involvement of demyelination in the development of chronic pain in which proteolipid protein (PLP), the major myelin protein of the CNS, may be an underappreciated but important player. In particular, we showed that the loss of PLP expression in mice led to sensitive dysfunctions (hypersensitivity to pain and mechanical allodynia) well before the development of motor dysfunctions. Later, another team described that PLP underexpression could be linked to thermal hypersensitivity and that restoring PLP expression could correct this behavioral alteration. Based on these recent data, and because PLP is strongly underexpressed in demyelinating lesions of MS, the general objective of our project is to better understand the involvement of this protein in the development of sensitive dysfunctions of MS and to propose a new therapeutic target. To achieve this objective, the master 2 internship will be divided into 2 work packages. One evaluating the corrective effect of spinal PLP overexpression (using viral vector-induced gene therapy) in an animal model of MS, namely experimental autoimmune encephalomyelitis (EAE) mice ). The second further characterizes the involvement of PLP in the modulation of sensitive perception using mice with conditional deletion of the Plp1 gene (neuronal vs. oligodendroglial inactivation). Since protein restoration by gene therapy is done quite easily in an animal model but still requires many adjustments for its use in humans, especially in common diseases of non-genetic origin, we need other tools to modify PLP expression. WP2 aims to pave the way for a more in-depth characterization of the cellular mechanisms of action of PLP in the modulation of sensitive perception in mice with the final objective (in the years to come) of proposing drugs capable of modulating the PLP signaling rather than its expression.

Profile :
We are looking for a highly motivated student, with training in neuroscience, pharmacology and/or cell biology, and willing to undertake a doctoral thesis after this internship. A validated qualification for animal testing is preferred.