Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion

Ohtomo, Ryo; Kinoshita, Keiji; Ohtomo, Gaku; Takase, Hajime; Hamanaka, Gen; Washida, Kazuo; Islam, Mohammad Rashedul; Wrann, Christiane D.; Katsuki, Hiroshi; Iwata, Atsushi; Lok, Josephine; Lo, Eng H.; Arai, Ken

doi:10.1007/s12975-019-00734-7

Cited by 26 publications

(32 citation statements)

References 37 publications

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“…Accordingly, we performed immunofluorescence (IF) staining for MBP (myelin basic protein), which is a major constituent of the myelin sheath in the brain [19], and for PDGFR␣ (platelet derived growth factor receptor ␣), which labels oligodendrocyte precursor cells [27,28], on hippocampal sections from mice that ran for nine weeks mice and sedentary controls. We first analyzed the corpus callosum because in different disease models, running exercise has been shown to increase myelinization in this brain region [5,29]. In line with these previous reports, we observed a 23% increase in MBP levels after nine weeks of running, though this was not significant (unpaired two-tailed ttest, p = 0.1616 ( Fig.…”

Section: Voluntary Running Enhances Myelinationsupporting

confidence: 79%

“…Some studies indicating that learning elevates hippocampal FA also noted effects on MBP, a main component of the myelin sheath, and GAP-43, a marker for axon remodeling [19,46]. Exercise has also been shown to raise oligodendrocyte precursor proliferation in mouse models [4,5], and a clinical study suggested myelination of the right parahippocampal cingulum is associated with physical activity in young healthy adults [66]. These results align with our findings, namely that running exercise increased the number of PDGFR␣ + oligodendroctyte precursor cells in the corpus callosum.…”

Section: Discussionmentioning

confidence: 99%

“…Mouse studies usually rely on analyzing tissues samples collected post mortem, whereas human studies must generally employ non-invasive neuroimaging techniques. Rodent models investigating neuroplasticity in the hippocampus show that exercise increases dendritic complexity; raises the number of dendritic spines; enhances synaptic plasticity; improves de novo neurogenesis, angiogenesis, and cerebral blood volume in the dentate gyrus; and elevates oligodendrocyte precursor proliferation [4][5][6][7][8][9][10]. In humans, exercise increases both hippocampal volume and cerebral blood flow to the hippocampus [7,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Diffusion tensor-MRI detects exercise-induced neuroplasticity in the hippocampal microstructure in mice

Islam

Luo

Valaris

et al. 2020

BPL

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Background: Despite considerable research on exercise-induced neuroplasticity in the brain, a major ongoing challenge in translating findings from animal studies to humans is that clinical and preclinical settings employ very different techniques. Objective: Here we aim to bridge this divide by using diffusion tensor imaging MRI (DTI), an advanced imaging technique commonly applied in human studies, in a longitudinal exercise study with mice. Methods: Wild-type mice were exercised using voluntary free-wheel running, and MRI scans were at baseline and after four weeks and nine weeks of running. Results: Both hippocampal volume and fractional anisotropy, a surrogate for microstructural directionality, significantly increased with exercise. In addition, exercise levels correlated with effect size. Histological analysis showed more PDGFRα+ oligodendrocyte precursor cells in the corpus callosum of running mice. Conclusions: These results provide compelling in vivo support for the concept that similar adaptive changes occur in the brains of mice and humans in response to exercise.

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Section: Voluntary Running Enhances Myelinationsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Diffusion tensor-MRI detects exercise-induced neuroplasticity in the hippocampal microstructure in mice

Islam

Luo

Valaris

et al. 2020

BPL

Self Cite

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“…The Morris water maze was performed to evaluate spatial and reference memory at 22 and 27 days postictus as previously described in [ 26 , 27 ]. After the training block trial, rats undergo 4 trial blocks to find the platform.…”

Section: Methodsmentioning

confidence: 99%

IL‐20R Activation via rIL‐19 Enhances Hematoma Resolution through the IL‐20R1/ERK/Nrf2 Pathway in an Experimental GMH Rat Pup Model

Liu

Flores

et al. 2021

Oxidative Medicine and Cellular Longevity

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Aims. Blood clots play the primary role in neurological deficits after germinal matrix hemorrhage (GMH). Previous studies have shown a beneficial effect in blood clot clearance after hemorrhagic stroke. The purpose of this study is to investigate interleukin-19’s role in hematoma clearance after GMH and its underlying mechanism of IL-20R1/ERK/Nrf2 signaling pathway. Methods. A total of 240 Sprague-Dawley P7 rat pups were used. GMH was induced by intraparenchymal injection of bacterial collagenase. rIL-19 was administered intranasally 1 hour post-GMH. IL-20R1 CRISPR was administered intracerebroventricularly, or Nrf2 antagonist ML385 was administered intraperitoneally 48 hours and 1 hour before GMH induction, respectively. Neurobehavior, Western blot, immunohistochemistry, histology, and hemoglobin assay were used to evaluate treatment regiments in the short- and long-term. Results. Endogenous IL-19, IL-20R1, IL-20R2, and scavenger receptor CD163 were increased after GMH. rIL-19 treatment improved neurological deficits, reduced hematoma volume and hemoglobin content, reduced ventriculomegaly, and attenuated cortical thickness loss. Additionally, treatment increased ERK, Nrf2, and CD163 expression, whereas IL-20R1 CRISPR-knockdown plasmid and ML385 inhibited the effects of rIL-19 on CD163 expression. Conclusion. rIL-19 treatment improved hematoma clearance and attenuated neurological deficits induced by GMH, which was mediated through the upregulation of the IL-20R1/ERK/Nrf2 pathways. rIL-19 treatment may provide a promising therapeutic strategy for the GMH patient population.

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“…Global cerebral ischemia-reperfusion injury (GCI) that occurs during the arrest period and subsequent return of spontaneous circulation (ROSC), trigger deleterious injury mechanisms including neuroinflammation [4] leading to irreversible brain damage [5]. Besides many other neurofunctional impairments [6], damage to the ischemia vulnerable brain regions such as hippocampus results in cognitive dysfunction following CA [7][8][9]. Cognitive impairment may persist up to 3 years, thereby hindering patients' daily activities and decreasing their quality of life [10].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of mast cell tryptase attenuates neuroinflammation via PAR-2/p38/NFκB pathway following asphyxial cardiac arrest in rats

Ocak

Huang

et al. 2020

J Neuroinflammation

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Background: Cardiac arrest survivors suffer from neurological dysfunction including cognitive impairment. Cerebral mast cells, the key regulators of neuroinflammation contribute to neuroinflammation-associated cognitive dysfunction. Mast cell tryptase was demonstrated to have a proinflammatory effect on microglia via the activation of microglial protease-activated receptor-2 (PAR-2). This study investigated the potential anti-neuroinflammatory effect of mast cell tryptase inhibition and the underlying mechanism of PAR-2/p-p38/NFκB signaling following asphyxia-induced cardiac arrest in rats. Methods: Adult male Sprague-Dawley rats resuscitated from 10 min of asphyxia-induced cardiac arrest were randomized to four separate experiments including time-course, short-term outcomes, long-term outcomes and mechanism studies. The effect of mast cell tryptase inhibition on asphyxial cardiac arrest outcomes was examined after intranasal administration of selective mast cell tryptase inhibitor (APC366; 50 μg/rat or 150 μg/rat). AC55541 (selective PAR-2 activator; 30 μg/rat) and SB203580 (selective p38 inhibitor; 300 μg/rat) were used for intervention. Short-term neurocognitive functions were evaluated using the neurological deficit score, number of seizures, adhesive tape removal test, and T-maze test, while long-term cognitive functions were evaluated using the Morris water maze test. Hippocampal neuronal degeneration was evaluated by Fluoro-Jade C staining.

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Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion

Cited by 26 publications

References 37 publications

Diffusion tensor-MRI detects exercise-induced neuroplasticity in the hippocampal microstructure in mice

Diffusion tensor-MRI detects exercise-induced neuroplasticity in the hippocampal microstructure in mice

IL‐20R Activation via rIL‐19 Enhances Hematoma Resolution through the IL‐20R1/ERK/Nrf2 Pathway in an Experimental GMH Rat Pup Model

Inhibition of mast cell tryptase attenuates neuroinflammation via PAR-2/p38/NFκB pathway following asphyxial cardiac arrest in rats

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