A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model
Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performanc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
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| Series: | Current Research in Neurobiology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665945X22000122 |
| _version_ | 1811201770371678208 |
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| author | Wang Zhuo Adam J. Lundquist Erin K. Donahue Yumei Guo Derek Phillips Giselle M. Petzinger Michael W. Jakowec Daniel P. Holschneider |
| author_facet | Wang Zhuo Adam J. Lundquist Erin K. Donahue Yumei Guo Derek Phillips Giselle M. Petzinger Michael W. Jakowec Daniel P. Holschneider |
| author_sort | Wang Zhuo |
| collection | DOAJ |
| description | Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performance in PD but its role in cognitive function remains poorly eludicated. In this study in a rodent model of PD, we sought to examine whether exercise improves cognitive processing and flexibility, important features of EF. Rats received 6-hydroxydopamine lesions of the bilateral striatum (caudate-putamen, CPu), specifically the dorsomedial CPu, a brain region central to EF. Rats were exercised on motorized running wheels or horizontal treadmills for 6–12 weeks. EF-related behaviors including attention and processing, as well as flexibility (inhibition) were evaluated using either an operant 3-choice serial reaction time task (3-CSRT) with rule reversal (3-CSRT-R), or a T-maze task with reversal. Changes in striatal transcript expression of dopamine receptors (Drd1-4) and synaptic proteins (Synaptophysin, PSD-95) were separately examined following 4 weeks of exercise in a subset of rats. Exercise/Lesion rats showed a modest, yet significant improvement in processing-related response accuracy in the 3-CSRT-R and T-maze, as well as a significant improvement in cognitive flexibility as assessed by inhibitory aptitude in the 3-CSRT-R. By four weeks, exercise also elicited increased expression of Drd1, Drd3, Drd4, synaptophysin, and PSD-95 in the dorsomedial and dorsolateral CPu. Our results underscore the observation that exercise, in addition to improving motor function may benefit cognitive performance, specifically EF, and that early changes (by 4 weeks) in CPu dopamine modulation and synaptic connectivity may underlie these benefits. |
| first_indexed | 2024-04-12T02:27:30Z |
| format | Article |
| id | doaj.art-230d708754664aad909e44e81bcc4ba7 |
| institution | Directory Open Access Journal |
| issn | 2665-945X |
| language | English |
| last_indexed | 2024-04-12T02:27:30Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Neurobiology |
| spelling | doaj.art-230d708754664aad909e44e81bcc4ba72022-12-22T03:51:56ZengElsevierCurrent Research in Neurobiology2665-945X2022-01-013100039A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat modelWang Zhuo0Adam J. Lundquist1Erin K. Donahue2Yumei Guo3Derek Phillips4Giselle M. Petzinger5Michael W. Jakowec6Daniel P. Holschneider7Department of Psychiatry and the Behavioral Sciences, University of Southern California, 1333 San Pablo St., Los Angeles, CA, 90033, USANeuroscience Graduate Program, University of Southern California, Los Angeles, CA, 90089, USANeuroscience Graduate Program, University of Southern California, Los Angeles, CA, 90089, USADepartment of Psychiatry and the Behavioral Sciences, University of Southern California, 1333 San Pablo St., Los Angeles, CA, 90033, USANeuroscience Graduate Program, University of Southern California, Los Angeles, CA, 90089, USADepartment of Neurology, University of Southern California, 1333 San Pablo St., Los Angeles, CA, 90033, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, 90089, USADepartment of Neurology, University of Southern California, 1333 San Pablo St., Los Angeles, CA, 90033, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, 90089, USADepartment of Neurology, University of Southern California, 1333 San Pablo St., Los Angeles, CA, 90033, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, 90089, USA; Department of Psychiatry and the Behavioral Sciences, University of Southern California, 1333 San Pablo St., Los Angeles, CA, 90033, USA; Corresponding author. Department of Psychiatry and the Behavioral Sciences, University of Southern California, 1975 Zonal Ave., KAM 400, MC9037, Los Angeles, CA, 90089-9037, USA.Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performance in PD but its role in cognitive function remains poorly eludicated. In this study in a rodent model of PD, we sought to examine whether exercise improves cognitive processing and flexibility, important features of EF. Rats received 6-hydroxydopamine lesions of the bilateral striatum (caudate-putamen, CPu), specifically the dorsomedial CPu, a brain region central to EF. Rats were exercised on motorized running wheels or horizontal treadmills for 6–12 weeks. EF-related behaviors including attention and processing, as well as flexibility (inhibition) were evaluated using either an operant 3-choice serial reaction time task (3-CSRT) with rule reversal (3-CSRT-R), or a T-maze task with reversal. Changes in striatal transcript expression of dopamine receptors (Drd1-4) and synaptic proteins (Synaptophysin, PSD-95) were separately examined following 4 weeks of exercise in a subset of rats. Exercise/Lesion rats showed a modest, yet significant improvement in processing-related response accuracy in the 3-CSRT-R and T-maze, as well as a significant improvement in cognitive flexibility as assessed by inhibitory aptitude in the 3-CSRT-R. By four weeks, exercise also elicited increased expression of Drd1, Drd3, Drd4, synaptophysin, and PSD-95 in the dorsomedial and dorsolateral CPu. Our results underscore the observation that exercise, in addition to improving motor function may benefit cognitive performance, specifically EF, and that early changes (by 4 weeks) in CPu dopamine modulation and synaptic connectivity may underlie these benefits.http://www.sciencedirect.com/science/article/pii/S2665945X22000122 |
| spellingShingle | Wang Zhuo Adam J. Lundquist Erin K. Donahue Yumei Guo Derek Phillips Giselle M. Petzinger Michael W. Jakowec Daniel P. Holschneider A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model Current Research in Neurobiology |
| title | A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model |
| title_full | A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model |
| title_fullStr | A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model |
| title_full_unstemmed | A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model |
| title_short | A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model |
| title_sort | mind in motion exercise improves cognitive flexibility impulsivity and alters dopamine receptor gene expression in a parkinsonian rat model |
| url | http://www.sciencedirect.com/science/article/pii/S2665945X22000122 |
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