Moderate Intensity Treadmill Exercise Increases Survival of Newborn Hippocampal Neurons and Improves Neurobehavioral Outcomes after Traumatic Brain Injury

Karelina, Kate; Schneiderman, Katarina; Shah, Sarthak; Fitzgerald, Julie; Cruz, Ruth Velazquez; Oliverio, Robin; Whitehead, Bailey; Yang, Jingzhen; Weil, Zachary M.

doi:10.1089/neu.2020.7389

Cited by 21 publications

(7 citation statements)

References 89 publications

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“…41 Moreover, 10 days of moderate-intensity treadmill exercise improved anxiety-like behavior and promoted the neurogenesis in mice with traumatic brain injury. 42 In the study, consistent and regular moderate treadmill exercise for the VCD mice was performed from the onset of estrous cycle prolongation until to acyclic.…”

Section: Discussionmentioning

confidence: 99%

Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD‐induced menopausal mice

et al. 2023

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AimsAs the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to alleviate anxiety and depression and the bone‐derived hormone osteocalcin has been reported to be necessary to prevent anxiety‐like behaviors. The aim of this study was to investigate the effects of exercise on anxiety behaviors in climacteric mice and whether it was related to osteocalcin.MethodsMenopausal mouse model was induced by intraperitoneal injection of 4‐vinylcyclohexene diepoxide (VCD). Open field, elevated plus maze, and light–dark tests were used to detect anxious behavior in mice. The content of serum osteocalcin was measured and its correlation with anxiety behavior was analyzed. BRDU and NEUN co‐localization cells were detected with immunofluorescence. Western blot was applied to obtain apoptosis‐related proteins.ResultsThe VCD mice showed obvious anxiety‐like behaviors and 10 weeks of treadmill exercise significantly ameliorated the anxiety and increased circulating osteocalcin in VCD mice. Exercise increased the number of BRDU and NEUN co‐localization cells in hippocampal dentate gyrus, reduced the number of impaired hippocampal neurons, inhibited the expression of BAX, cleaved Caspase3, and cleaved PARP, promoted the expression of BCL‐2. Importantly, circulating osteocalcin levels were positively associated with the improvements of anxiety, the number of BRDU and NEUN co‐localization cells in hippocampal dentate gyrus and negatively related to impaired hippocampal neurons.ConclusionExercise ameliorates anxiety behavior, promotes hippocampal dentate gyrus neurogenesis, and inhibits hippocampal cell apoptosis in VCD‐induced menopausal mice. They are related to circulating osteocalcin, which are increased by exercise.

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Section: Discussionmentioning

confidence: 99%

Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD‐induced menopausal mice

et al. 2023

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“…In contrast, repeat mTBI mice (but not single mTBI mice) have increased activity in the light cycle for the first 72 h post-injury [ 45 ]. It is also worth noting that the use of enriched environments, exercise and BDNF are known to improve outcomes after TBI [ 55 , 56 ], and we cannot rule out that our use of stimulating environments and the ability to run on average 9–10 km every 24 h may have improved brain health and reduced our ability to detect circadian changes after TBI.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Traumatic Brain Injury on Sleep Architecture and Circadian Rhythms in Mice—A Comparison of High-Frequency Head Impact and Controlled Cortical Injury

Korthas

Main

Harvey

et al. 2022

Biology

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Traumatic brain injury (TBI) is a significant risk factor for the development of sleep and circadian rhythm impairments. In this study we compare the circadian rhythms and sleep patterns in the high-frequency head impact (HFHI) and controlled cortical impact (CCI) mouse models of TBI. These mouse models have different injury mechanisms key differences of pathology in brain regions controlling circadian rhythms and EEG wave generation. We found that both HFHI and CCI caused dysregulation in the diurnal expression of core circadian genes (Bmal1, Clock, Per1,2, Cry1,2) at 24 h post-TBI. CCI mice had reduced locomotor activity on running wheels in the first 7 d post-TBI; however, both CCI and HFHI mice were able to maintain circadian behavior cycles even in the absence of light cues. We used implantable EEG to measure sleep cycles and brain activity and found that there were no differences in the time spent awake, in NREM or REM sleep in either TBI model. However, in the sleep states, CCI mice have reduced delta power in NREM sleep and reduced theta power in REM sleep at 7 d post-TBI. Our data reveal that different types of brain trauma can result in distinct patterns of circadian and sleep disruptions and can be used to better understand the etiology of sleep disorders after TBI.

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“…Axonal degeneration was observed based on silver staining in the white matter tracts of the forebrain. The silver score was determined as previously reported qualitatively using a point-value system: such that 0 = little to no axonal degeneration, 1 = sparse silver staining limited to the corpus callosum, 2 = moderate silver staining in the corpus callosum and other white matter tracts, and 3 = very dense silver staining throughout multiple white matter tracts ( Karelina et al, 2021 ). All analyses were performed blind to experimental conditions.…”

Section: Methodsmentioning

confidence: 99%

Ovarian Steroids Mediate Sex Differences in Alcohol Reward After Brain Injury in Mice

Oliverio

Fitzgerald

Velazquez-Cruz

et al. 2022

Front. Behav. Neurosci.

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Intoxication is a leading risk factor for injury, and TBI increases the risk for later alcohol misuse, especially when the injury is sustained in childhood. Previously, we modeled this pattern in mice, wherein females injured at postnatal day 21 drank significantly more than uninjured females, while we did not see this effect in males. However, the biological underpinnings of this sex difference have remained elusive. In this study, we utilize this preclinical model and traditional endocrine manipulations to assess the effect of perinatal sex steroids on post-injury ethanol response. We found that perinatal androgen administration and adult ovariectomy prevented the development of conditioned place preference to ethanol in females, while there was not an effect of gonadectomy either developmental time point on the severity of axonal degeneration. Finally, although TBI increased the number of microglia in males, there was no corresponding effect of gonadectomy, which suggests that males exhibit prolonged neuroinflammation after brain injury irrespective of circulating sex steroids. Taken together, our results indicate a potential role for ovarian sex steroids in the development of greater alcohol preference after a juvenile TBI in female mice.

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Moderate Intensity Treadmill Exercise Increases Survival of Newborn Hippocampal Neurons and Improves Neurobehavioral Outcomes after Traumatic Brain Injury

Cited by 21 publications

References 89 publications

Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD‐induced menopausal mice

Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD‐induced menopausal mice

The Effect of Traumatic Brain Injury on Sleep Architecture and Circadian Rhythms in Mice—A Comparison of High-Frequency Head Impact and Controlled Cortical Injury

Ovarian Steroids Mediate Sex Differences in Alcohol Reward After Brain Injury in Mice

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