Aerobic exercise modulates the striatal Erk/MAPK signaling pathway and improves LID in a mouse model of Parkinson's disease
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
OBJECTIVE: To investigate the role of the striatal extracellular signal-regulated kinase (Erk1/2) and its phosphorylation (p-Erk1/2) in aerobic training to alleviate the development of the L-DOPA induced dyskinesia (LID) in PD mice.
METHODS: Forty-eight male C57BL/6 N mice were randomly divided into the 6-OHDA surgery group (6-OHDA, n=42) and the sham surgery group (Sham, n=6). A two-point injection of 6-OHDA into the right striatum was used to establish a lateralized injury PD model. PD mice were randomly divided into a PD control group (PD, n=13) and a PD exercise group (PDE, n=16), this is followed by 4 weeks of L-DOPA treatment, and PDE mice received concurrent running table training (18 m/min, 40 min/day, 5 times/week). AIM scores were performed weekly, and mice were assessed for motor function after 4 weeks using the rotarod, open field, and gait tests. Immunohistochemistry was used to test nigrostriatal TH expression, Western blot was used to determine Erk1/2 and p-Erk1/2 protein expression, and immunofluorescence double-labeling technique was used to detect Erk1/2 and p-Erk1/2 co-expression with prodynorphin (PDYN).
RESULTS: (1) All AIM scores of PD and PDE mice increased significantly (P < 0.05) with the prolongation of L-DOPA treatment. Compared with PD, all AIM scores were significantly lower in PDE mice (P < 0.05). (2) After 4 weeks, the motor function of PD mice was significantly reduced compared with Sham (P < 0.05 or P < 0.01); compared with PD, the motor function of PDE mice was significantly increased (P < 0.05). (3) Compared with Sham, the expression of Erk1/2 protein, the number of positive cells of Erk1/2 and p-Erk1/2 and the number of positive cells co-expressed with PDYN were significantly increased in PD mice (P < 0.05); compared with PD, Erk1/2 protein expression was significantly decreased in PDE mice (P < 0.05), and the number of Erk1/2 and p-Erk1/2 positive cells was significantly reduced (P < 0.05).
CONCLUSION: 4 weeks of aerobic exercise can effectively alleviate the development of L-DOPA-induced dyskinesia and improve motor function in PD mice. The related mechanism may be related to the inhibition of striatal Erk/MAPK signaling pathway overactivation by aerobic exercise, but this change did not occur selectively in D1-MSNs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:209 |
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| Enthalten in: |
Brain research bulletin - 209(2024) vom: 30. März, Seite 110906 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Fangyuan [VerfasserIn] |
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| Links: |
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| Themen: |
46627O600J |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 28.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.brainresbull.2024.110906 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368850900 |
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| 100 | 1 | |a Zhou, Fangyuan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Aerobic exercise modulates the striatal Erk/MAPK signaling pathway and improves LID in a mouse model of Parkinson's disease |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 25.03.2024 | ||
| 500 | |a Date Revised 28.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a OBJECTIVE: To investigate the role of the striatal extracellular signal-regulated kinase (Erk1/2) and its phosphorylation (p-Erk1/2) in aerobic training to alleviate the development of the L-DOPA induced dyskinesia (LID) in PD mice | ||
| 520 | |a METHODS: Forty-eight male C57BL/6 N mice were randomly divided into the 6-OHDA surgery group (6-OHDA, n=42) and the sham surgery group (Sham, n=6). A two-point injection of 6-OHDA into the right striatum was used to establish a lateralized injury PD model. PD mice were randomly divided into a PD control group (PD, n=13) and a PD exercise group (PDE, n=16), this is followed by 4 weeks of L-DOPA treatment, and PDE mice received concurrent running table training (18 m/min, 40 min/day, 5 times/week). AIM scores were performed weekly, and mice were assessed for motor function after 4 weeks using the rotarod, open field, and gait tests. Immunohistochemistry was used to test nigrostriatal TH expression, Western blot was used to determine Erk1/2 and p-Erk1/2 protein expression, and immunofluorescence double-labeling technique was used to detect Erk1/2 and p-Erk1/2 co-expression with prodynorphin (PDYN) | ||
| 520 | |a RESULTS: (1) All AIM scores of PD and PDE mice increased significantly (P < 0.05) with the prolongation of L-DOPA treatment. Compared with PD, all AIM scores were significantly lower in PDE mice (P < 0.05). (2) After 4 weeks, the motor function of PD mice was significantly reduced compared with Sham (P < 0.05 or P < 0.01); compared with PD, the motor function of PDE mice was significantly increased (P < 0.05). (3) Compared with Sham, the expression of Erk1/2 protein, the number of positive cells of Erk1/2 and p-Erk1/2 and the number of positive cells co-expressed with PDYN were significantly increased in PD mice (P < 0.05); compared with PD, Erk1/2 protein expression was significantly decreased in PDE mice (P < 0.05), and the number of Erk1/2 and p-Erk1/2 positive cells was significantly reduced (P < 0.05) | ||
| 520 | |a CONCLUSION: 4 weeks of aerobic exercise can effectively alleviate the development of L-DOPA-induced dyskinesia and improve motor function in PD mice. The related mechanism may be related to the inhibition of striatal Erk/MAPK signaling pathway overactivation by aerobic exercise, but this change did not occur selectively in D1-MSNs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Aerobic exercise | |
| 650 | 4 | |a Erk/MAPK signaling pathway | |
| 650 | 4 | |a LID | |
| 650 | 4 | |a Parkinson's disease | |
| 650 | 4 | |a Striatum | |
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| 650 | 7 | |a Levodopa |2 NLM | |
| 650 | 7 | |a 46627O600J |2 NLM | |
| 650 | 7 | |a Oxidopamine |2 NLM | |
| 650 | 7 | |a 8HW4YBZ748 |2 NLM | |
| 700 | 1 | |a Wei, Longwei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yinhao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Wei |e verfasserin |4 aut | |
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