Serotonin reuptake inhibitors improve muscle stem cell function and muscle regeneration in male mice

Mylène Fefeu, Michael Blatzer, Anita Kneppers, David Briand, Pierre Rocheteau, Alexandre Haroche, David Hardy, Mélanie Juchet-Martin, Anne Danckaert, François Coudoré, Abdulkarim Tutakhail, Corinne Huchet, Aude Lafoux, Rémi Mounier, Olivier Mir, Raphaël Gaillard () and Fabrice Chrétien ()
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Mylène Fefeu: Service Hospitalo-Universitaire de psychiatrie
Michael Blatzer: Global Health Department
Anita Kneppers: Univ Lyon
David Briand: Global Health Department
Pierre Rocheteau: Global Health Department
Alexandre Haroche: Service Hospitalo-Universitaire de psychiatrie
David Hardy: Global Health Department
Mélanie Juchet-Martin: Global Health Department
Anne Danckaert: UTechS PBI
François Coudoré: Université Paris-Saclay
Abdulkarim Tutakhail: Université Paris-Saclay
Corinne Huchet: CHU Nantes
Aude Lafoux: IRS 2 Nantes Biotech
Rémi Mounier: Univ Lyon
Olivier Mir: Gustave Roussy
Raphaël Gaillard: Service Hospitalo-Universitaire de psychiatrie
Fabrice Chrétien: Global Health Department

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Serotonin reuptake inhibitor antidepressants such as fluoxetine are widely used to treat mood disorders. The mechanisms of action include an increase in extracellular level of serotonin, neurogenesis, and growth of vessels in the brain. We investigated whether fluoxetine could have broader peripheral regenerative properties. Following prolonged administration of fluoxetine in male mice, we showed that fluoxetine increases the number of muscle stem cells and muscle angiogenesis, associated with positive changes in skeletal muscle function. Fluoxetine also improved skeletal muscle regeneration after single and multiples injuries with an increased muscle stem cells pool and vessel density associated with reduced fibrotic lesions and inflammation. Mice devoid of peripheral serotonin treated with fluoxetine did not exhibit beneficial effects during muscle regeneration. Specifically, pharmacological, and genetic inactivation of the 5-HT1B subtype serotonin receptor also abolished the enhanced regenerative process induced by fluoxetine. We highlight here a regenerative property of serotonin on skeletal muscle.

Date: 2024
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DOI: 10.1038/s41467-024-50220-4

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