Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function
Physical inactivity is the 4th leading cause of death globally and has been shown to significantly increase the risk for developing Alzheimer’s Disease (AD). Recent work has demonstrated that exercise prior to breeding produces heritable benefits to the brains of offspring, suggesting that the physi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1147420/full |
| _version_ | 1797854037637332992 |
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| author | Nathan R. Kerr Taylor J. Kelty Taylor J. Kelty Xuansong Mao Thomas E. Childs David D. Kline David D. Kline David D. Kline R. Scott Rector R. Scott Rector R. Scott Rector Frank W. Booth Frank W. Booth Frank W. Booth Frank W. Booth |
| author_facet | Nathan R. Kerr Taylor J. Kelty Taylor J. Kelty Xuansong Mao Thomas E. Childs David D. Kline David D. Kline David D. Kline R. Scott Rector R. Scott Rector R. Scott Rector Frank W. Booth Frank W. Booth Frank W. Booth Frank W. Booth |
| author_sort | Nathan R. Kerr |
| collection | DOAJ |
| description | Physical inactivity is the 4th leading cause of death globally and has been shown to significantly increase the risk for developing Alzheimer’s Disease (AD). Recent work has demonstrated that exercise prior to breeding produces heritable benefits to the brains of offspring, suggesting that the physical activity status of previous generations could play an important role in one’s brain health and their subsequent risk for neurodegenerative diseases. Thus, our study aimed to test the hypothesis that selective breeding for physical inactivity, or for high physical activity, preference produces heritable deficits and enhancements to brain health, respectively. To evaluate this hypothesis, male and female sedentary Low Voluntary Runners (LVR), wild type (WT), and High Voluntary Runner (HVR) rats underwent cognitive behavioral testing, analysis of hippocampal neurogenesis and mitochondrial respiration, and molecular analysis of the dentate gyrus. These analyses revealed that selecting for physical inactivity preference has produced major detriments to cognition, brain mitochondrial respiration, and neurogenesis in female LVR while female HVR display enhancements in brain glucose metabolism and hippocampal size. On the contrary, male LVR and HVR showed very few differences in these parameters relative to WT. Overall, we provide evidence that selective breeding for physical inactivity has a heritable and detrimental effect on brain health and that the female brain appears to be more susceptible to these effects. This emphasizes the importance of remaining physically active as chronic intergenerational physical inactivity likely increases susceptibility to neurodegenerative diseases for both the inactive individual and their offspring. |
| first_indexed | 2024-04-09T19:59:24Z |
| format | Article |
| id | doaj.art-2f613e6b9f704748aee29e529cd6e607 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-09T19:59:24Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-2f613e6b9f704748aee29e529cd6e6072023-04-03T05:16:04ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-04-011510.3389/fnagi.2023.11474201147420Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic functionNathan R. Kerr0Taylor J. Kelty1Taylor J. Kelty2Xuansong Mao3Thomas E. Childs4David D. Kline5David D. Kline6David D. Kline7R. Scott Rector8R. Scott Rector9R. Scott Rector10Frank W. Booth11Frank W. Booth12Frank W. Booth13Frank W. Booth14Department of Biomedical Sciences, University of Missouri, Columbia, MO, United StatesDepartment of Biomedical Sciences, University of Missouri, Columbia, MO, United StatesDepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, United StatesDepartment of Biomedical Sciences, University of Missouri, Columbia, MO, United StatesDepartment of Biomedical Sciences, University of Missouri, Columbia, MO, United StatesDepartment of Biomedical Sciences, University of Missouri, Columbia, MO, United StatesDepartment of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, United StatesDalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United StatesDepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, United StatesResearch Service, Harry S. Truman Memorial Veterans Hospital, University of Missouri, Columbia, MO, United StatesDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO, United StatesDepartment of Biomedical Sciences, University of Missouri, Columbia, MO, United StatesDepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, United StatesDepartment of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, United StatesDalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United StatesPhysical inactivity is the 4th leading cause of death globally and has been shown to significantly increase the risk for developing Alzheimer’s Disease (AD). Recent work has demonstrated that exercise prior to breeding produces heritable benefits to the brains of offspring, suggesting that the physical activity status of previous generations could play an important role in one’s brain health and their subsequent risk for neurodegenerative diseases. Thus, our study aimed to test the hypothesis that selective breeding for physical inactivity, or for high physical activity, preference produces heritable deficits and enhancements to brain health, respectively. To evaluate this hypothesis, male and female sedentary Low Voluntary Runners (LVR), wild type (WT), and High Voluntary Runner (HVR) rats underwent cognitive behavioral testing, analysis of hippocampal neurogenesis and mitochondrial respiration, and molecular analysis of the dentate gyrus. These analyses revealed that selecting for physical inactivity preference has produced major detriments to cognition, brain mitochondrial respiration, and neurogenesis in female LVR while female HVR display enhancements in brain glucose metabolism and hippocampal size. On the contrary, male LVR and HVR showed very few differences in these parameters relative to WT. Overall, we provide evidence that selective breeding for physical inactivity has a heritable and detrimental effect on brain health and that the female brain appears to be more susceptible to these effects. This emphasizes the importance of remaining physically active as chronic intergenerational physical inactivity likely increases susceptibility to neurodegenerative diseases for both the inactive individual and their offspring.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1147420/fullhippocampusphysical inactivitysedentaryneurodegenerationbrain healthphysical activity |
| spellingShingle | Nathan R. Kerr Taylor J. Kelty Taylor J. Kelty Xuansong Mao Thomas E. Childs David D. Kline David D. Kline David D. Kline R. Scott Rector R. Scott Rector R. Scott Rector Frank W. Booth Frank W. Booth Frank W. Booth Frank W. Booth Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function Frontiers in Aging Neuroscience hippocampus physical inactivity sedentary neurodegeneration brain health physical activity |
| title | Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function |
| title_full | Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function |
| title_fullStr | Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function |
| title_full_unstemmed | Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function |
| title_short | Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function |
| title_sort | selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function |
| topic | hippocampus physical inactivity sedentary neurodegeneration brain health physical activity |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1147420/full |
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