Exercise hormone irisin is a critical regulator of cognitive function

被引：266

作者：

Islam, Mohammad R. ^{[1
,2
]}

Valaris, Sophia ^{[1
,2
]}

Young, Michael F. ^{[1
,2
]}

Haley, Erin B. ^{[1
,2
]}

Luo, Renhao ^{[1
,2
]}

Bond, Sabrina F. ^{[1
,2
,3
]}

Mazuera, Sofia ^{[1
,2
,3
]}

Kitchen, Robert R. ^{[1
,2
]}

Caldarone, Barbara J. ^{[2
,4
]}

Bettio, Luis E. B. ^{[5
]}

Christie, Brian R. ^{[5
]}

Schmider, Angela B. ^{[2
,6
]}

Soberman, Roy J. ^{[2
,6
]}

Besnard, Antoine ^{[2
,7
]}

Jedrychowski, Mark P. ^{[8
,9
]}

Kim, Hyeonwoo ^{[8
,9
]}

Tu, Hua ^{[10
]}

Kim, Eunhee ^{[11
,12
]}

Choi, Se Hoon ^{[11
,12
]}

Tanzi, Rudolph E. ^{[11
,12
]}

Spiegelman, Bruce M. ^{[8
,9
]}

Wrann, Christiane D. ^{[1
,2
,12
]}

机构：

[1] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Northeastern Univ, Program Behav Neurosci, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Harvard NeuroDiscovery Ctr, 75 Francis St, Boston, MA 02115 USA

[5] Univ Victoria, Div Med Sci, Victoria, BC, Canada

[6] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA

[7] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[8] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[9] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA

[10] LakePharma, San Carlos, CA USA

[11] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA USA

[12] Massachusetts Gen Hosp, McCance Ctr Brain Hlth, Boston, MA 02114 USA

来源：

NATURE METABOLISM | 2021年 / 3卷 / 08期

关键词：

ADULT HIPPOCAMPAL NEUROGENESIS; DENTATE GYRUS; PATTERN SEPARATION; WATER-MAZE; AEROBIC EXERCISE; GRANULE CELLS; NEURAL STEM; IN-VIVO; MICE; MEMORY;

D O I：

10.1038/s42255-021-00438-z

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer's disease, probably through its direct action in the brain. 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.

引用

页码：1058 / +

页数：24

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