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Irisin stimulates protective signaling pathways in rat hippocampal neurons

Physical exercise stimulates neuroprotective pathways, has pro-cognitive actions, and alleviates memory impairment in Alzheimer’s disease (AD). Irisin is an exercise-linked hormone produced by cleavage of fibronectin type III domain containing protein 5 (FNDC5) in skeletal muscle, brain and other ti...

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Autores principales: Lourenco, Mychael V., de Freitas, Guilherme B., Raony, Ícaro, Ferreira, Sergio T., De Felice, Fernanda G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518673/
https://www.ncbi.nlm.nih.gov/pubmed/36187295
http://dx.doi.org/10.3389/fncel.2022.953991
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author Lourenco, Mychael V.
de Freitas, Guilherme B.
Raony, Ícaro
Ferreira, Sergio T.
De Felice, Fernanda G.
author_facet Lourenco, Mychael V.
de Freitas, Guilherme B.
Raony, Ícaro
Ferreira, Sergio T.
De Felice, Fernanda G.
author_sort Lourenco, Mychael V.
collection PubMed
description Physical exercise stimulates neuroprotective pathways, has pro-cognitive actions, and alleviates memory impairment in Alzheimer’s disease (AD). Irisin is an exercise-linked hormone produced by cleavage of fibronectin type III domain containing protein 5 (FNDC5) in skeletal muscle, brain and other tissues. Irisin was recently shown to mediate the brain benefits of exercise in AD mouse models. Here, we sought to obtain insight into the neuroprotective actions of irisin. We demonstrate that adenoviral-mediated expression of irisin promotes extracellular brain derived neurotrophic factor (BDNF) accumulation in hippocampal cultures. We further show that irisin stimulates transient activation of extracellular signal-regulated kinase 1/2 (ERK 1/2), and prevents amyloid-β oligomer-induced oxidative stress in primary hippocampal neurons. Finally, analysis of RNA sequencing (RNAseq) datasets shows a trend of reduction of hippocampal FNDC5 mRNA with aging and tau pathology in humans. Results indicate that irisin activates protective pathways in hippocampal neurons and further support the notion that stimulation of irisin signaling in the brain may be beneficial in AD.
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spelling pubmed-95186732022-09-29 Irisin stimulates protective signaling pathways in rat hippocampal neurons Lourenco, Mychael V. de Freitas, Guilherme B. Raony, Ícaro Ferreira, Sergio T. De Felice, Fernanda G. Front Cell Neurosci Neuroscience Physical exercise stimulates neuroprotective pathways, has pro-cognitive actions, and alleviates memory impairment in Alzheimer’s disease (AD). Irisin is an exercise-linked hormone produced by cleavage of fibronectin type III domain containing protein 5 (FNDC5) in skeletal muscle, brain and other tissues. Irisin was recently shown to mediate the brain benefits of exercise in AD mouse models. Here, we sought to obtain insight into the neuroprotective actions of irisin. We demonstrate that adenoviral-mediated expression of irisin promotes extracellular brain derived neurotrophic factor (BDNF) accumulation in hippocampal cultures. We further show that irisin stimulates transient activation of extracellular signal-regulated kinase 1/2 (ERK 1/2), and prevents amyloid-β oligomer-induced oxidative stress in primary hippocampal neurons. Finally, analysis of RNA sequencing (RNAseq) datasets shows a trend of reduction of hippocampal FNDC5 mRNA with aging and tau pathology in humans. Results indicate that irisin activates protective pathways in hippocampal neurons and further support the notion that stimulation of irisin signaling in the brain may be beneficial in AD. Frontiers Media S.A. 2022-09-09 /pmc/articles/PMC9518673/ /pubmed/36187295 http://dx.doi.org/10.3389/fncel.2022.953991 Text en Copyright © 2022 Lourenco, de Freitas, Raony, Ferreira and De Felice. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Lourenco, Mychael V.
de Freitas, Guilherme B.
Raony, Ícaro
Ferreira, Sergio T.
De Felice, Fernanda G.
Irisin stimulates protective signaling pathways in rat hippocampal neurons
title Irisin stimulates protective signaling pathways in rat hippocampal neurons
title_full Irisin stimulates protective signaling pathways in rat hippocampal neurons
title_fullStr Irisin stimulates protective signaling pathways in rat hippocampal neurons
title_full_unstemmed Irisin stimulates protective signaling pathways in rat hippocampal neurons
title_short Irisin stimulates protective signaling pathways in rat hippocampal neurons
title_sort irisin stimulates protective signaling pathways in rat hippocampal neurons
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518673/
https://www.ncbi.nlm.nih.gov/pubmed/36187295
http://dx.doi.org/10.3389/fncel.2022.953991
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