Anatomy and Cell Biology Publications

Title

Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models

Authors

Mychael V. Lourenco, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro
Rudimar L. Fozza, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro
Guilherme B. de Freitas, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro
Hong Zhang, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University
Grasielle C. Kincheski, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro
Felipe C. Ribeiro, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro
Rafaella A. Goncalves, Centre for Neuroscience Studies, Queen's University
Julia R. Clarke, School of Pharmacy, Federal University of Rio de Janeiro
Danielle Beckman, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro
Agnieszka Staniszewski, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University
Hanna Berman, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University
Lorena A. Guerra, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro
Leticia Forny-Germano, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro
Shelby Meier, Sanders-Brown Center on Aging, University of Kentucky
Donna M. Wilcock, Sanders-Brown Center on Aging, University of Kentucky, Lexington
Jorge M. de Souza, Division of Neurosurgery, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro
Soniza Alves-Leon, Division of Neurology/Epilepsy Program, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro
Vania F. Prado, Robarts Research Institute, University of Western Ontario
Marco A.M. Prado, Robarts Research Institute, University of Western Ontario
Jose F. Abisambra, Sanders-Brown Center on Aging, University of Kentucky
Fernanda Tovar-Moll, D'Or Institute for Research and Education , Rio de Janeiro
Paulo Mattos, Institute of Psychiatry, Federal University of Rio de Janeiro
Ottavio Arancio, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University
Sergio T. Ferreira, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro
Fernanda G. De Felice, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro

Document Type

Article

Publication Date

1-2019

Issue

1

Journal

Nature Medicine

Volume

25

First Page

165

Last Page

175

URL with Digital Object Identifier

https://doi.org/10.1038/s41591-018-0275-4

Abstract

Defective brain hormonal signaling has been associated with Alzheimer's disease (AD), a disorder characterized by synapse and memory failure. Irisin is an exercise-induced myokine released on cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), also expressed in the hippocampus. Here we show that FNDC5/irisin levels are reduced in AD hippocampi and cerebrospinal fluid, and in experimental AD models. Knockdown of brain FNDC5/irisin impairs long-term potentiation and novel object recognition memory in mice. Conversely, boosting brain levels of FNDC5/irisin rescues synaptic plasticity and memory in AD mouse models. Peripheral overexpression of FNDC5/irisin rescues memory impairment, whereas blockade of either peripheral or brain FNDC5/irisin attenuates the neuroprotective actions of physical exercise on synaptic plasticity and memory in AD mice. By showing that FNDC5/irisin is an important mediator of the beneficial effects of exercise in AD models, our findings place FNDC5/irisin as a novel agent capable of opposing synapse failure and memory impairment in AD.

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