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Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulated in Exercise in a Mouse Model of Parkinson’s Disease
BACKGROUND: Exercise plays an essential role in improving motor symptoms in Parkinson’s disease (PD), but the underlying mechanism in the central nervous system remains unclear. METHODS: Motor ability was observed after 12-week treadmill exercise on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MP...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260255/ https://www.ncbi.nlm.nih.gov/pubmed/35813950 http://dx.doi.org/10.3389/fnagi.2022.891644 |
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author | Tong, Weifang Zhang, Kunshan Yao, Hongkai Li, Lixi Hu, Yong Zhang, Jingxing Song, Yunping Guan, Qiang Li, Siguang Sun, Yi E. Jin, Lingjing |
author_facet | Tong, Weifang Zhang, Kunshan Yao, Hongkai Li, Lixi Hu, Yong Zhang, Jingxing Song, Yunping Guan, Qiang Li, Siguang Sun, Yi E. Jin, Lingjing |
author_sort | Tong, Weifang |
collection | PubMed |
description | BACKGROUND: Exercise plays an essential role in improving motor symptoms in Parkinson’s disease (PD), but the underlying mechanism in the central nervous system remains unclear. METHODS: Motor ability was observed after 12-week treadmill exercise on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. RNA-sequencing on four brain regions (cerebellum, cortex, substantia nigra (SN), and striatum) from control animals, MPTP-induced PD, and MPTP-induced PD model treated with exercise for 12 weeks were performed. Transcriptional networks on the four regions were further identified by an integrative network biology approach. RESULTS: The 12-week treadmill exercise significantly improved the motor ability of an MPTP-induced mouse model of PD. RNA-seq analysis showed SN and striatum were remarkably different among individual region’s response to exercise in the PD model. Especially, synaptic regulation pathways about axon guidance, synapse assembly, neurogenesis, synaptogenesis, transmitter transport-related pathway, and synaptic regulation genes, including Neurod2, Rtn4rl2, and Cd5, were upregulated in SN and striatum. Lastly, immunofluorescence staining revealed that exercise rescued the loss of TH(+) synapses in the striatal region in PD mice, which validates the key role of synaptic regulation pathways in exercise-induced protective effects in vivo. CONCLUSION: SN and striatum are important brain regions in which critical transcriptional changes, such as in synaptic regulation pathways, occur after the exercise intervention on the PD model. |
format | Online Article Text |
id | pubmed-9260255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92602552022-07-08 Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulated in Exercise in a Mouse Model of Parkinson’s Disease Tong, Weifang Zhang, Kunshan Yao, Hongkai Li, Lixi Hu, Yong Zhang, Jingxing Song, Yunping Guan, Qiang Li, Siguang Sun, Yi E. Jin, Lingjing Front Aging Neurosci Neuroscience BACKGROUND: Exercise plays an essential role in improving motor symptoms in Parkinson’s disease (PD), but the underlying mechanism in the central nervous system remains unclear. METHODS: Motor ability was observed after 12-week treadmill exercise on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. RNA-sequencing on four brain regions (cerebellum, cortex, substantia nigra (SN), and striatum) from control animals, MPTP-induced PD, and MPTP-induced PD model treated with exercise for 12 weeks were performed. Transcriptional networks on the four regions were further identified by an integrative network biology approach. RESULTS: The 12-week treadmill exercise significantly improved the motor ability of an MPTP-induced mouse model of PD. RNA-seq analysis showed SN and striatum were remarkably different among individual region’s response to exercise in the PD model. Especially, synaptic regulation pathways about axon guidance, synapse assembly, neurogenesis, synaptogenesis, transmitter transport-related pathway, and synaptic regulation genes, including Neurod2, Rtn4rl2, and Cd5, were upregulated in SN and striatum. Lastly, immunofluorescence staining revealed that exercise rescued the loss of TH(+) synapses in the striatal region in PD mice, which validates the key role of synaptic regulation pathways in exercise-induced protective effects in vivo. CONCLUSION: SN and striatum are important brain regions in which critical transcriptional changes, such as in synaptic regulation pathways, occur after the exercise intervention on the PD model. Frontiers Media S.A. 2022-06-23 /pmc/articles/PMC9260255/ /pubmed/35813950 http://dx.doi.org/10.3389/fnagi.2022.891644 Text en Copyright © 2022 Tong, Zhang, Yao, Li, Hu, Zhang, Song, Guan, Li, Sun and Jin. 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 Tong, Weifang Zhang, Kunshan Yao, Hongkai Li, Lixi Hu, Yong Zhang, Jingxing Song, Yunping Guan, Qiang Li, Siguang Sun, Yi E. Jin, Lingjing Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulated in Exercise in a Mouse Model of Parkinson’s Disease |
title | Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulated in Exercise in a Mouse Model of Parkinson’s Disease |
title_full | Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulated in Exercise in a Mouse Model of Parkinson’s Disease |
title_fullStr | Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulated in Exercise in a Mouse Model of Parkinson’s Disease |
title_full_unstemmed | Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulated in Exercise in a Mouse Model of Parkinson’s Disease |
title_short | Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulated in Exercise in a Mouse Model of Parkinson’s Disease |
title_sort | transcriptional profiling reveals brain region-specific gene networks regulated in exercise in a mouse model of parkinson’s disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260255/ https://www.ncbi.nlm.nih.gov/pubmed/35813950 http://dx.doi.org/10.3389/fnagi.2022.891644 |
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