6533b858fe1ef96bd12b6d73
RESEARCH PRODUCT
Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing
Graziana SpotoMichele VecchioAngela Maria AmoriniMichelino Di RosaRosalba ParentiRosario GulinoNunzio VicarioGrazia ScanduraFederica M. SpitaleCiro BottaSimona D’aprileG. LeanzaMassimo GulisanoGiuseppe LazzarinoJoshua D. BernstockEmanuele BurattiDaniele TibulloCristiana AlberghinaCesarina GiallongoRenata MangioneRenata MangioneMiriam Wissam SaabRobert ZorecGiovanni Li Voltisubject
MaleCancer ResearchPhysiology129 StrainBiochemistryMiceDatabases GeneticMedicineMyocyteMotor NeuronsNeuronal PlasticitySkeletalSmoothened ReceptorHedgehog signaling pathwayMuscle atrophyMitochondriaAstrogliosisNeuroprotective AgentsMusclemedicine.symptomInflammation MediatorsSignal TransductionCholera ToxinMice 129 StrainhedgehogImmunologyMotor ActivityNeuroprotectionArticleDatabasesCellular and Molecular NeurosciencesmoothenedGeneticAnimalsHumansHedgehog ProteinsMuscle SkeletalHedgehogGlucocorticoidsMuscle DenervationQH573-671Animalbusiness.industryAmyotrophic Lateral SclerosisGlial biologyCell Biologymedicine.diseaseSaporinsSpineMitochondria MuscleDisease Models AnimalclobetasolinflammationCase-Control StudiesDisease ModelsDiseases of the nervous systemCytologySmoothenedbusinessEnergy MetabolismNeuroscienceOpen Field Testdescription
AbstractMotoneuronal 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-06-01 |