Biology subjects

Stheneur, P.

Publications and source records attributed to Stheneur, P..

2 recordsLinked to original sources

bioRxiv2025

Neuronal activity promotes repair by microglial reprogramming following demyelination

Microglia, the resident immune cells of the central nervous system (CNS), play a multifaceted role in neurological disorders. In multiple sclerosis (MS), a chronic demyelinating and neurodegenerative disease, microglia contribute to inflammation and tissue damage, but can also support repair by clearing myelin debris, limiting inflammation and promoting remyelination and neuroprotection. The timely transition from their pro-inflammatory to pro-regenerative states is essential for effective repair and, in chronic MS, persistent, defective microglial activation contributes to disease progression. Yet, the mechanisms underlying the microglial switch remain largely unknown. In this study, we demonstrate that neuronal activity can modulate microglial signature at the onset of remyelination in MS models, in a pattern-dependent manner. Transcriptomic analyses reveal a downregulation of pro-inflammatory, disease-associated microglial signatures alongside an upregulation of genes associated with oxidative phosphorylation and lipid metabolism, indicative of a shift toward pro-regenerative states following physiological activity enhancement. This activity-dependent reprogramming also extends to infiltrating monocytes and macrophages, collectively fostering a microenvironment favoring repair.

neuroscience↗

bioRxiv2024

Neuronal activity promotes axonal node-like clustering prior to myelination and remyelination in the central nervous system.

Nodes of Ranvier ensure the fast saltatory conduction along myelinated axons, through their enrichment in voltage-gated sodium and potassium channels. We and others have shown that node-like cluster assembly can occur before myelination. In multiple sclerosis, demyelination is associated with node of Ranvier disassembly, but node-like reassembly can occur prior to remyelination. Given the crucial role of neuronal activity in inducing (re)myelination, we asked whether neuronal activity could regulate node-like clustering. We show that node-like clustering is promoted by neuronal activity and decreased when excitatory glutamatergic receptors are inhibited. Altering glutamatergic neurotransmission leads to the downregulation of Nav1.1 expression, which we show to be critical for node-like clustering. Neuronal activity also promotes node-like clustering in remyelination. As node-like clusters modulate conduction velocity and myelination initiation along axons, we propose that activity-dependent node-like clustering could modulate neuronal network establishment, as well as myelination regulation and patterning during development, plasticity and repair.

neuroscience↗