Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke

Abstract In stroke patients, loss of skeletal muscle mass leads to prolonged weakness and less efficient rehabilitation. We previously showed that expression of myostatin, a master negative regulator of skeletal muscle mass, was strongly increased in skeletal muscle in a mouse model of stroke. We th...

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Autores principales: Marine Maud Desgeorges, Xavier Devillard, Jérome Toutain, Josiane Castells, Didier Divoux, David Frédéric Arnould, Christopher Haqq, Myriam Bernaudin, Anne-Cécile Durieux, Omar Touzani, Damien Gilles Freyssenet
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/ad0c911773f74bc491f220592714b3a1
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spelling oai:doaj.org-article:ad0c911773f74bc491f220592714b3a12021-12-02T11:41:10ZPharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke10.1038/s41598-017-13912-02045-2322https://doaj.org/article/ad0c911773f74bc491f220592714b3a12017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13912-0https://doaj.org/toc/2045-2322Abstract In stroke patients, loss of skeletal muscle mass leads to prolonged weakness and less efficient rehabilitation. We previously showed that expression of myostatin, a master negative regulator of skeletal muscle mass, was strongly increased in skeletal muscle in a mouse model of stroke. We therefore tested the hypothesis that myostatin inhibition would improve recovery of skeletal muscle mass and function after cerebral ischemia. Cerebral ischemia (45 minutes) was induced by intraluminal right middle cerebral artery occlusion (MCAO). Swiss male mice were randomly assigned to Sham-operated mice (n = 10), MCAO mice receiving the vehicle (n = 15) and MCAO mice receiving an anti-myostatin PINTA745 (n = 12; subcutaneous injection of 7.5 mg.kg−1 PINTA745 immediately after surgery, 3, 7 and 10 days after MCAO). PINTA745 reduced body weight loss and improved body weight recovery after cerebral ischemia, as well as muscle strength and motor function. PINTA745 also increased muscle weight recovery 15 days after cerebral ischemia. Mechanistically, the better recovery of skeletal muscle mass in PINTA745-MCAO mice involved an increased expression of genes encoding myofibrillar proteins. Therefore, an anti-myostatin strategy can improve skeletal muscle recovery after cerebral ischemia and may thus represent an interesting strategy to combat skeletal muscle loss and weakness in stroke patients.Marine Maud DesgeorgesXavier DevillardJérome ToutainJosiane CastellsDidier DivouxDavid Frédéric ArnouldChristopher HaqqMyriam BernaudinAnne-Cécile DurieuxOmar TouzaniDamien Gilles FreyssenetNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Marine Maud Desgeorges
Xavier Devillard
Jérome Toutain
Josiane Castells
Didier Divoux
David Frédéric Arnould
Christopher Haqq
Myriam Bernaudin
Anne-Cécile Durieux
Omar Touzani
Damien Gilles Freyssenet
Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke
description Abstract In stroke patients, loss of skeletal muscle mass leads to prolonged weakness and less efficient rehabilitation. We previously showed that expression of myostatin, a master negative regulator of skeletal muscle mass, was strongly increased in skeletal muscle in a mouse model of stroke. We therefore tested the hypothesis that myostatin inhibition would improve recovery of skeletal muscle mass and function after cerebral ischemia. Cerebral ischemia (45 minutes) was induced by intraluminal right middle cerebral artery occlusion (MCAO). Swiss male mice were randomly assigned to Sham-operated mice (n = 10), MCAO mice receiving the vehicle (n = 15) and MCAO mice receiving an anti-myostatin PINTA745 (n = 12; subcutaneous injection of 7.5 mg.kg−1 PINTA745 immediately after surgery, 3, 7 and 10 days after MCAO). PINTA745 reduced body weight loss and improved body weight recovery after cerebral ischemia, as well as muscle strength and motor function. PINTA745 also increased muscle weight recovery 15 days after cerebral ischemia. Mechanistically, the better recovery of skeletal muscle mass in PINTA745-MCAO mice involved an increased expression of genes encoding myofibrillar proteins. Therefore, an anti-myostatin strategy can improve skeletal muscle recovery after cerebral ischemia and may thus represent an interesting strategy to combat skeletal muscle loss and weakness in stroke patients.
format article
author Marine Maud Desgeorges
Xavier Devillard
Jérome Toutain
Josiane Castells
Didier Divoux
David Frédéric Arnould
Christopher Haqq
Myriam Bernaudin
Anne-Cécile Durieux
Omar Touzani
Damien Gilles Freyssenet
author_facet Marine Maud Desgeorges
Xavier Devillard
Jérome Toutain
Josiane Castells
Didier Divoux
David Frédéric Arnould
Christopher Haqq
Myriam Bernaudin
Anne-Cécile Durieux
Omar Touzani
Damien Gilles Freyssenet
author_sort Marine Maud Desgeorges
title Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke
title_short Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke
title_full Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke
title_fullStr Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke
title_full_unstemmed Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke
title_sort pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/ad0c911773f74bc491f220592714b3a1
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