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Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/β5 in Parkinson’s Disease

Parkinson’s disease with cognitive impairment (PD-CI) results in several clinical outcomes for which specific treatment is lacking. Although the pathogenesis of PD-CI has not yet been fully elucidated, it is related to neuronal plasticity decline in the hippocampus region. The dopaminergic projectio...

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Autores principales: Tang, Chuanxi, Liu, Mengting, Zhou, Zihang, Li, Hao, Yang, Chenglin, Yang, Li, Xiang, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178565/
https://www.ncbi.nlm.nih.gov/pubmed/37175535
http://dx.doi.org/10.3390/ijms24097830
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author Tang, Chuanxi
Liu, Mengting
Zhou, Zihang
Li, Hao
Yang, Chenglin
Yang, Li
Xiang, Jie
author_facet Tang, Chuanxi
Liu, Mengting
Zhou, Zihang
Li, Hao
Yang, Chenglin
Yang, Li
Xiang, Jie
author_sort Tang, Chuanxi
collection PubMed
description Parkinson’s disease with cognitive impairment (PD-CI) results in several clinical outcomes for which specific treatment is lacking. Although the pathogenesis of PD-CI has not yet been fully elucidated, it is related to neuronal plasticity decline in the hippocampus region. The dopaminergic projections from the substantia nigra to the hippocampus are critical in regulating hippocampal plasticity. Recently, aerobic exercise has been recognized as an effective therapeutic strategy for enhancing plasticity through the secretion of various muscle factors. The exact role of FNDC5—an upregulated, newly identified myokine produced after exercise—in mediating hippocampal plasticity and regional dopaminergic projections in PD-CI remains unclear. In this study, the effect of treadmill exercise on hippocampal synaptic plasticity was evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced chronic PD models. The results showed that treadmill exercise substantially alleviated the motor dysfunction, cognition disorder, and dopaminergic neuron degeneration induced by MPTP. Here, we discovered that the quadriceps, serum, and brain FNDC5 levels were lower in PD mice and that intervention with treadmill exercise restored FNDC5 levels. Moreover, treadmill exercise enhanced the synaptic plasticity of hippocampal pyramidal neurons via increased dopamine levels and BDNF in the PD mice. The direct protective effect of FNDC5 is achieved by promoting the secretion of BDNF in the hippocampal neurons via binding the integrin αVβ5 receptor, thereby improving synaptic plasticity. Regarding the indirect protection effect, FNDC5 promotes the dopaminergic connection from the substantia nigra to the hippocampus by mediating the interaction between the integrin αVβ5 of the hippocampal neurons and the CD90 molecules on the membrane of dopaminergic terminals. Our findings demonstrated that treadmill exercise could effectively alleviate cognitive disorders via the activation of the FNDC5–BDNF pathway and enhance the dopaminergic synaptic connection from SNpc to the hippocampus in the MPTP-induced chronic PD model.
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spelling pubmed-101785652023-05-13 Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/β5 in Parkinson’s Disease Tang, Chuanxi Liu, Mengting Zhou, Zihang Li, Hao Yang, Chenglin Yang, Li Xiang, Jie Int J Mol Sci Article Parkinson’s disease with cognitive impairment (PD-CI) results in several clinical outcomes for which specific treatment is lacking. Although the pathogenesis of PD-CI has not yet been fully elucidated, it is related to neuronal plasticity decline in the hippocampus region. The dopaminergic projections from the substantia nigra to the hippocampus are critical in regulating hippocampal plasticity. Recently, aerobic exercise has been recognized as an effective therapeutic strategy for enhancing plasticity through the secretion of various muscle factors. The exact role of FNDC5—an upregulated, newly identified myokine produced after exercise—in mediating hippocampal plasticity and regional dopaminergic projections in PD-CI remains unclear. In this study, the effect of treadmill exercise on hippocampal synaptic plasticity was evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced chronic PD models. The results showed that treadmill exercise substantially alleviated the motor dysfunction, cognition disorder, and dopaminergic neuron degeneration induced by MPTP. Here, we discovered that the quadriceps, serum, and brain FNDC5 levels were lower in PD mice and that intervention with treadmill exercise restored FNDC5 levels. Moreover, treadmill exercise enhanced the synaptic plasticity of hippocampal pyramidal neurons via increased dopamine levels and BDNF in the PD mice. The direct protective effect of FNDC5 is achieved by promoting the secretion of BDNF in the hippocampal neurons via binding the integrin αVβ5 receptor, thereby improving synaptic plasticity. Regarding the indirect protection effect, FNDC5 promotes the dopaminergic connection from the substantia nigra to the hippocampus by mediating the interaction between the integrin αVβ5 of the hippocampal neurons and the CD90 molecules on the membrane of dopaminergic terminals. Our findings demonstrated that treadmill exercise could effectively alleviate cognitive disorders via the activation of the FNDC5–BDNF pathway and enhance the dopaminergic synaptic connection from SNpc to the hippocampus in the MPTP-induced chronic PD model. MDPI 2023-04-25 /pmc/articles/PMC10178565/ /pubmed/37175535 http://dx.doi.org/10.3390/ijms24097830 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tang, Chuanxi
Liu, Mengting
Zhou, Zihang
Li, Hao
Yang, Chenglin
Yang, Li
Xiang, Jie
Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/β5 in Parkinson’s Disease
title Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/β5 in Parkinson’s Disease
title_full Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/β5 in Parkinson’s Disease
title_fullStr Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/β5 in Parkinson’s Disease
title_full_unstemmed Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/β5 in Parkinson’s Disease
title_short Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/β5 in Parkinson’s Disease
title_sort treadmill exercise alleviates cognition disorder by activating the fndc5: dual role of integrin αv/β5 in parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178565/
https://www.ncbi.nlm.nih.gov/pubmed/37175535
http://dx.doi.org/10.3390/ijms24097830
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