TY - JOUR
T1 - Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models
AU - Lourenco, Mychael V.
AU - Frozza, Rudimar L.
AU - de Freitas, Guilherme B.
AU - Zhang, Hong
AU - Kincheski, Grasielle C.
AU - Ribeiro, Felipe C.
AU - Gonçalves, Rafaella A.
AU - Clarke, Julia R.
AU - Beckman, Danielle
AU - Staniszewski, Agnieszka
AU - Berman, Hanna
AU - Guerra, Lorena A.
AU - Forny-Germano, Letícia
AU - Meier, Shelby
AU - Wilcock, Donna M.
AU - de Souza, Jorge M.
AU - Alves-Leon, Soniza
AU - Prado, Vania F.
AU - Prado, Marco A.M.
AU - Abisambra, Jose F.
AU - Tovar-Moll, Fernanda
AU - Mattos, Paulo
AU - Arancio, Ottavio
AU - Ferreira, Sergio T.
AU - De Felice, Fernanda G.
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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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U2 - 10.1038/s41591-018-0275-4
DO - 10.1038/s41591-018-0275-4
M3 - Article
C2 - 30617325
AN - SCOPUS:85059759869
SN - 1078-8956
VL - 25
SP - 165
EP - 175
JO - Nature Medicine
JF - Nature Medicine
IS - 1
ER -