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Équipe C. Faivre-Sarrailh

Accueil > Recherche > Équipe C. Faivre-Sarrailh > Neuron-glia interactions and neuropathology

Neuron-glia interactions and neuropathology


In myelinated axons, the action potentials are rapidly generated at nodes Ranvier. The nodal gap contains high densities of voltage-gated sodium Nav1.6 channels. In addition, voltage-gated potassium channels Kv1.1/1.2 are clustered at juxtaparanodes and regulate axonal excitability.

The architecture and function of the nodes of Ranvier depend on several specialized zones of cell contacts between the axon and myelinating glial cells, the nodes, paranodes and juxtaparanodes. We are interested in the molecular characterization of the axo-glial septate-like junctions at paranodes. Our studies provided new insights into the mechanisms regulating surface targeting, and clustering of ion channels and cell adhesion molecules (CAMs).

Alterations of axonal domain organization are associated with demyelinating neuropathies and participate to conduction and excitability defects. We have recently identified nodal and paranodal CAMs, such as Contactin, as primary targets of autoantibodies in peripheral neuropathies, such as the Guillain-Barré syndrome and CIDP. We also determine how these autoantibodies are pathogenic by preventing cell adhesion, mediating disruption of the nodes and conduction loss.

We also focus on Caspr2, a CAM associated with Kv1, which is an autoimmune target in limbic encephalitis. In addition, the gene coding for Caspr2, cntnap2 is associated with neuropsychiatric disorders such as the autism spectrum disorders, schizophrenia or language impairments. We recently reported that Caspr2 is selectively expressed by inhibitory neurons in hippocampal cell culture.

Another topic developed in our lab is the study of neuron-glia interactions in Huntington’s disease, a neuropathology resulting from increased length of a polyglutamine stretch in the Huntingtin protein. We combine Drosophila’s advanced genetic approaches with cellular analyses on primary cultured neurons. Our aim is to understand how glia contributes to energetic defect and abnormal neurotransmission in the disease. We recently showed that manipulation of glucose transporters or mitochondrial shaping genes confers protection against mutant Huntingtin toxicity.

 

 

 

C. Faivre-Sarrailh team

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