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Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing

Authors :
Graziana Spoto
Michele Vecchio
Angela Maria Amorini
Michelino Di Rosa
Rosalba Parenti
Rosario Gulino
Nunzio Vicario
Grazia Scandura
Federica M. Spitale
Cirino Botta
Simona D’Aprile
G. Leanza
Massimo Gulisano
Giuseppe Lazzarino
Joshua D. Bernstock
Emanuele Buratti
Daniele Tibullo
Cristiana Alberghina
Cesarina Giallongo
Renata Mangione
Miriam Wissam Saab
Robert Zorec
Giovanni Li Volti
Vicario N.
Spitale F.M.
Tibullo D.
Giallongo C.
Amorini A.M.
Scandura G.
Spoto G.
Saab M.W.
D'Aprile S.
Alberghina C.
Mangione R.
Bernstock J.D.
Botta C.
Gulisano M.
Buratti E.
Leanza G.
Zorec R.
Vecchio M.
Di Rosa M.
Li Volti G.
Lazzarino G.
Parenti R.
Gulino R.
Source :
Cell Death & Disease, Cell Death and Disease, Vol 12, Iss 7, Pp 1-13 (2021)
Publication Year :
2021
Publisher :
Springer Nature, 2021.

Abstract

Motoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and supporting spinal plasticity. These effects were coupled with reduced pro-inflammatory microglia and reactive astrogliosis, reduced muscle atrophy, and support of mitochondrial integrity and metabolism. Our results suggest that clobetasol stimulates a series of compensatory processes and therefore represents a translational approach for intractable denervating and neurodegenerative disorders.

Details

Language :
English
Database :
OpenAIRE
Journal :
Cell Death & Disease, Cell Death and Disease, Vol 12, Iss 7, Pp 1-13 (2021)
Accession number :
edsair.doi.dedup.....36418db7187bf323d52a6c3c731d3267