Treadmill exercise improves neurological function by inhibiting autophagy and the binding of HMGB1 to Beclin1 in MCAO juvenile rats

Pan, Guoyuan; Jin, Lingqin; Shen, Wei-Min; Zhang, Jieqiong; Pan, Juanjuan; Cheng, Jing-Yan; Xie, Qipeng; Hu, Quan; Wu, Shamin; Zhang, Hongmei; Chen, Xiang

doi:10.1016/j.lfs.2020.117279

Cited by 20 publications

(15 citation statements)

References 46 publications

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“…Recent work by our group substantiates these findings by demonstrating exercise-improved glycometabolism, decreased neuroinflammation, and apoptosis (Li et al, 2017a,b,c). The present results were largely supported by the findings of other groups, which demonstrated that exercise accelerated CBF (Pianta et al, 2019), decreased infarct volume (Tian et al, 2013;Pan et al, 2020) and improved functional outcomes (Pianta et al, 2019). In contrast, a few studies have reported no neuroprotective effects of exercise on the neurological deficit and infarct volume after stroke within 3 days (Matsuda et al, 2011;Cui et al, 2020).…”

Section: Discussionsupporting

confidence: 89%

In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

Huber

et al. 2020

Front. Cell. Neurosci.

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Although physical exercise has been demonstrated to augment recovery of the post-stroke brain, the question of what level of exercise intensity optimizes neurological outcomes of post-stroke rehabilitation remains unsettled. In this study, we aim to clarify the mechanisms underlying the intensity-dependent effect of exercise on neurologic function, and thereby to help direct the clinical application of exercisebased neurorehabilitation. To do this, we used a well-established rat model of ischemic stroke consisting of cerebral ischemia induction through middle cerebral artery occlusion (MCAO). Ischemic rats were subsequently assigned either to a control group entailing post-stroke rest or to one of two exercise groups distinguished by the intensity of their accompanying treadmill regimens. After 24 h of reperfusion, exercise was initiated. Infarct volume, apoptotic cell death, and neurological defects were quantified in all groups at 3 days, and motor and cognitive functions were tracked up to day-28. Additionally, Western blotting was used to assess the influence of our interventions on several proteins related to synaptogenesis and neuroplasticity (growth-associated protein 43, a microtubule-associated protein, postsynaptic density-95, synapsin I, hypoxia-inducible factor-1α, brain-derived neurotrophic factor, nerve growth factor, tyrosine kinase B, and cAMP response element-binding protein). Our results were in equal parts encouraging and surprising. Both mild and intense exercise significantly decreased infarct volume, cell death, and neurological deficits. Motor and cognitive function, as determined using an array of tests such as beam balance, forelimb placing, and the Morris water maze, were also significantly improved by both exercise protocols. Interestingly, while an obvious enhancement of neuroplasticity proteins was shown in both exercise groups, mild exercise rats demonstrated a stronger effect on the expressions of Tau (p < 0.01), brain-derived neurotrophic factor (p < 0.01), and tyrosine kinase B (p < 0.05). These findings contribute to the growing body of literature regarding the positive effects of both mild and intense long-term treadmill exercise on brain injury, functional outcome, and

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Section: Discussionsupporting

confidence: 89%

In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

Huber

et al. 2020

Front. Cell. Neurosci.

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“…HMGB1 was shown to bind to Beclin1, which is involved in the recruitment of autophagy-related proteins, to maintain autophagy. In a rat model of childhood stroke, the authors showed that treadmill exercise alleviates neurological damage by inhibiting autophagy via blocking the binding of HMGB1 to Belin1 (Pan et al, 2020). Collectively, these results indicated that HMGB1 plays an important role in regulating autophagic pathways during cerebral ischemia-reperfusion (Pan et al, 2020).…”

Section: Toll-like Receptors (Tlrs)mentioning

confidence: 94%

“…Inhibition of the NLRP3 inflammasome activation may have a neuroprotective role after cerebral ischemia (Li et al, 2020). Recent research by Pan et al (2020) revealed connections between HMGB1 and autophagy in an MCAO model in juvenile rats. HMGB1 was shown to bind to Beclin1, which is involved in the recruitment of autophagy-related proteins, to maintain autophagy.…”

Section: Toll-like Receptors (Tlrs)mentioning

confidence: 99%

“…In addition to the above strategies, several other strategies have been proposed to inhibit HMGB1, including peptides and proteins, physical methods, chemicals, and clinical drugs. For example, in the MCAO juvenile rat model, treadmill exercise inhibited cell autophagy in the ischemic penumbra by inhibiting HMGB1 translocation and its binding with Beclin1 to improve neurological function (Pan et al, 2020).…”

Section: Othersmentioning

confidence: 99%

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The Roles of High Mobility Group Box 1 in Cerebral Ischemic Injury

Gou

Ying

Yan

et al. 2020

Front. Cell. Neurosci.

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High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that plays an important role in stabilizing nucleosomes and DNA repair. HMGB1 can be passively released from necrotic neurons or actively secreted by microglia, macrophages/monocytes, and neutrophils. Cerebral ischemia is a major cause of mortality and disability worldwide, and its outcome depends on the number of neurons dying due to hypoxia in the ischemic area. HMGB1 contributes to the pathogenesis of cerebral ischemia via mediating neuroinflammatory responses to cerebral ischemic injury. Extracellular HMGB1 regulates many neuroinflammatory events by interacting with its different cell surface receptors, such as receptors for advanced glycation end products, toll-like receptor (TLR)-2, and TLR-4. Additionally, HMGB1 can be redox-modified, thus exerting specific cellular functions in the ischemic brain and has different roles in the acute and late stages of cerebral ischemic injury. However, the role of HMGB1 in cerebral ischemia is complex and remains unclear. Herein, we summarize and review the research on HMGB1 in cerebral ischemia, focusing especially on the role of HMGB1 in hypoxic ischemia in the immature brain and in white matter ischemic injury. We also outline the possible mechanisms of HMGB1 in cerebral ischemia and the main strategies to inhibit HMGB1 pertaining to its potential as a novel critical molecular target in cerebral ischemic injury.

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“…Exercise plays an essential role in controlling inflammatory diseases such as diabetes by reducing the secretion of inflammatory cytokines and increasing the secretion of anti-inflammatory cytokines [14]. Aerobic exercise reduces HMGB1 levels in the blood and tissue of diabetic rats [15] and blocks the middle cerebral artery in an experimental model of rats [16]. However, finding the exact mechanisms of aerobic exercise effects on HMGB1 gene expression and related mechanisms requires further studies in diabetic patients.…”

mentioning

confidence: 99%

Effect of a 6-week Aerobic Exercise Program on High-mobility Group Box 1 Gene Expression in Aortic Tissue of Diabetic Rats

et al. 2021

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Aims: Type 2 diabetes is a rising problem and a significant risk factor for small and large vessel disease. The present study aims to investigate the effect of a 6-week aerobic exercise program on High-mobility Group Box 1 (HMGB1) gene expression in aortic tissue of diabetic rats. Methods & Materials: In this experimental study, 40 male rats aged 8 weeks were randomly selected. Once familiarized with the exercise protocol, they were divided into four groups of healthy-control (n=10), diabetic-control (n=10), healthy-exercise (n=10), and diabetic-exercise (n=10). Type 2 diabetes was first induced, and then the rats run on a treadmill for 6 weeks, 5 sessions per week. After 12-14 h of fasting and 72 h after the last session, aortic tissue sampling was performed for HMGB1 analysis by quantitative real-time polymerase chain reaction (q-RT PCR) technique. Data analysis was performed using 1-way ANOVA and Tukey post hoc test at the significant level of P<0.05. Findings: Induction of type 2 diabetes led to a significant increase in HMGB1 gene expression in rats (P=0.001), significantly reduced following aerobic exercise (P=0.003). Aerobic exercise also reduced the expression of the HMGB1 gene in healthy rats (P=0.000). Conclusion: Aerobic exercise may have a protective effect by reducing the HMGB1 gene expression in the aortic tissue of diabetic rats. It can be used as an effective non-pharmacological method to improve diabetes-induced inflammation and prevent vascular disorders.

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Treadmill exercise improves neurological function by inhibiting autophagy and the binding of HMGB1 to Beclin1 in MCAO juvenile rats

Cited by 20 publications

References 46 publications

In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

The Roles of High Mobility Group Box 1 in Cerebral Ischemic Injury

Effect of a 6-week Aerobic Exercise Program on High-mobility Group Box 1 Gene Expression in Aortic Tissue of Diabetic Rats

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