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Exercise hormone irisin is a critical regulator of cognitive function.
Islam, Mohammad R; Valaris, Sophia; Young, Michael F; Haley, Erin B; Luo, Renhao; Bond, Sabrina F; Mazuera, Sofia; Kitchen, Robert R; Caldarone, Barbara J; Bettio, Luis E B; Christie, Brian R; Schmider, Angela B; Soberman, Roy J; Besnard, Antoine; Jedrychowski, Mark P; Kim, Hyeonwoo; Tu, Hua; Kim, Eunhee; Choi, Se Hoon; Tanzi, Rudolph E; Spiegelman, Bruce M; Wrann, Christiane D.
Afiliação
  • Islam MR; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Valaris S; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Young MF; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Haley EB; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Luo R; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Bond SF; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Mazuera S; Program in Behavioral Neuroscience, Northeastern University, Boston, MA, USA.
  • Kitchen RR; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Caldarone BJ; Program in Behavioral Neuroscience, Northeastern University, Boston, MA, USA.
  • Bettio LEB; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Christie BR; Harvard NeuroDiscovery Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Schmider AB; Division of Medical Sciences, University of Victoria, Victoria, British Colombia, Canada.
  • Soberman RJ; Division of Medical Sciences, University of Victoria, Victoria, British Colombia, Canada.
  • Besnard A; Nephrology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Jedrychowski MP; Nephrology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Kim H; Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Tu H; Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
  • Kim E; Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
  • Choi SH; LakePharma, San Carlos, CA, USA.
  • Tanzi RE; MassGeneral Institute for Neurodegenerative Disease, Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
  • Spiegelman BM; McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
  • Wrann CD; MassGeneral Institute for Neurodegenerative Disease, Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Nat Metab ; 3(8): 1058-1070, 2021 08.
Article em En | MEDLINE | ID: mdl-34417591
ABSTRACT
Identifying secreted mediators that drive the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in ageing or Alzheimer's disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the benefits of exercise on cognitive function. Genetic deletion of Fndc5/irisin (global Fndc5 knock-out (KO) mice; F5KO) impairs cognitive function in exercise, ageing and AD. Diminished pattern separation in F5KO mice can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KO mice, adult-born neurons in the dentate gyrus are morphologically, transcriptionally and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral delivery of irisin via adeno-associated viral overexpression in the liver results in enrichment of central irisin and is sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of the cognitive benefits of exercise and is a potential therapeutic agent for treating cognitive disorders including AD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Condicionamento Físico Animal / Fibronectinas / Cognição / Hormônios Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Nat Metab Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Condicionamento Físico Animal / Fibronectinas / Cognição / Hormônios Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Nat Metab Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos