Autophagy suppression by exercise pretreatment and p38 inhibition is neuroprotective in cerebral ischemia

Zhang, Li; Niu, Wenxiu; He, Zhaoyi; Zhang, Qi; Wu, Yi; Jiang, Congyu; Tang, Chaozheng; Hu, Ya-Han; Jia, Jie

doi:10.1016/j.brainres.2014.08.067

Cited by 29 publications

(11 citation statements)

References 54 publications

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“…Upregulating the autophagy lever caused by oxidative damage is detrimental to neural survival and proliferation . Suppression of excessive autophagic activation through pharmacological or genetic methods may be a novel target to reduce reactive zinc‐induced neurons and astrocytes death and alleviate the brain infarction after ischaemia injury . These findings support the possibility that correcting autophagic dysfunction may be a potential therapeutic strategy for repairing nerve injury.…”

Section: Discussionmentioning

confidence: 71%

Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death

Zhu

et al. 2018

J Cellular Molecular Medi

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Seeking for effective drugs which are beneficial to facilitating axonal regrowth and elongation after peripheral nerve injury (PNI) has gained extensive attention. Fibroblast growth factor 21 (FGF21) is a metabolic factor that regulates blood glucose and lipid homeostasis. However, there is little concern for the potential protective effect of FGF21 on nerve regeneration after PNI and revealing related molecular mechanisms. Here, we firstly found that exogenous FGF21 administration remarkably promoted functional and morphologic recovery in a rat model of sciatic crush injury, manifesting as persistently improved motor and sensory function, enhanced axonal remyelination and regrowth and accelerated Schwann cells (SCs) proliferation. Furthermore, local FGF21 application attenuated the excessive activation of oxidative stress, which was accompanied with the activation of nuclear factor erythroid‐2‐related factor 2 (Nrf‐2) transcription and extracellular regulated protein kinases (ERK) phosphorylation. We detected FGF21 also suppressed autophagic cell death in SCs. Additionally, treatment with the ERK inhibitor U0126 or autophagy inhibitor 3‐MA partially abolishes anti‐oxidant effect and reduces SCs death. Taken together, these results indicated that the role of FGF21 in remyelination and nerve regeneration after PNI was probably related to inhibit the excessive activation of ERK/Nrf‐2 signalling‐regulated oxidative stress and autophagy‐induced cell death. Overall, our work suggests that FGF21 administration may provide a new therapy for PNI.

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Section: Discussionmentioning

confidence: 71%

Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death

Zhu

et al. 2018

J Cellular Molecular Medi

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“…Beneficial effects can result from facilitating cerebellar reserve both in terms of activation of neuroprotective mechanisms, and of stimulation of circuit maturation. It is worth noting that the impact of motor exercise on autophagy regulation with neuroprotective effects has been shown also in other neurological pathologies [175][176][177]. Autophagy modulation can therefore add to the numerous mechanistic substrates through which experience-including exercise-molds the brain.…”

Section: Cellular Mechanisms Underlying Functional Cerebellar Reservementioning

confidence: 97%

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders

et al. 2019

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Cerebellar reserve refers to the capacity of the cerebellum to compensate for tissue damage or loss of function resulting from many different etiologies. When the inciting event produces acute focal damage (e.g., stroke, trauma), impaired cerebellar function may be compensated for by other cerebellar areas or by extracerebellar structures (i.e., structural cerebellar reserve). In contrast, when pathological changes compromise cerebellar neuronal integrity gradually leading to cell death (e.g., metabolic and immune-mediated cerebellar ataxias, neurodegenerative ataxias), it is possible that the affected area itself can compensate for the slowly evolving cerebellar lesion (i.e., functional cerebellar reserve). Here, we examine cerebellar reserve from the perspective of the three cornerstones of clinical ataxiology: control of ocular movements, coordination of voluntary axial and appendicular movements, and cognitive functions. Current evidence indicates that cerebellar reserve is potentiated by environmental enrichment through the mechanisms of autophagy and synaptogenesis, suggesting that cerebellar reserve is not rigid or fixed, but exhibits plasticity potentiated by experience. These conclusions have therapeutic implications. During the period when cerebellar reserve is preserved, treatments should be directed at stopping disease progression and/or limiting the pathological process. Simultaneously, cerebellar reserve may be potentiated using multiple approaches. Potentiation of cerebellar reserve may lead to compensation and restoration of function in the setting of cerebellar diseases, and also in disorders primarily of the cerebral hemispheres by enhancing cerebellar mechanisms of action. It therefore appears that cerebellar reserve, and the underlying plasticity of cerebellar microcircuitry that enables it, may be of critical neurobiological importance to a wide range of neurological/neuropsychiatric conditions.

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“…They also studied autophagy signaling as a possible mechanism. Their results revealed that exercise, by reducing the autophagy process in the cell, could play a role in cardiac protection from IR injury [13]. Lu et al (2018) argued that exercise preconditioning can reduce exhaustive exercise-induced myocardial injuries.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, preventing autophagy balance disruption during IR can reduce cellular and tissue damages. Exercise training can significantly affect cellular autophagy balance [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Studies report that exercise training reduces the myocardial infarct size in laboratory rats [5,8], and provides neuroprotection in cerebral ischemic injury via autophagy suppression [13]. Exercise training has obvious benefits in maintaining the autophagy process balance [11][12][13]. Exercise training, by modulating cellular autophagy, may play a cardiovascular protection role from IR injury.…”

Section: Introductionmentioning

confidence: 99%

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Preconditioning Effect of High-Intensity Aerobic Training on Myocardial Ischemia-Reperfusion Injury and Beclin-1 Gene Expression in Rats

Ghahremani

Salehi

Komaki‬

et al. 2018

PTJ

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Purpose: Ischemia-Reperfusion (IR) injury is one of the most common cardiac disorders leading to irreversible heart damage. Many underlying mechanisms seem to be involved, among which disruption of cellular autophagy balance. Since physical training has a beneficial effect on the improvement of autophagy balance, it may have a cardioprotective effect against IR injury. This study investigates the protective role of aerobic training from cardiac IR injury and the autophagy process as a possible mechanism.Methods: Thirty-two male Wistar rats (8 weeks old) were divided into control, sham, control plus IR, and training plus IR groups (8 rats each). The training group was exercised aerobically on a treadmill for 8 weeks (5 d/wk). After 8 weeks, the anesthetized rats underwent left thoracotomy (sham, control plus IR, and training plus IR groups) to access the left anterior descending coronary artery, which was occluded by a silk suture for 30 min and then released for 90 min of reperfusion (IR groups). Triphenyltetrazolium chloride staining was used to determine the infarct size. The gene expression of Beclin-1 was evaluated by real-time polymerase chain reaction. One-way ANOVA was used for statistical analysis with the significance level set at P≤0.05. Results:The cardiac infarct size was smaller in training plus IR (20.24±5.7%) group compared to that in the control plus IR (35.9±2.3%) group (P≤0.05). On the other hand, IR operation significantly increased the gene expression of Beclin-1, while exercise training prevented expression of the mentioned gene in training plus IR group (P≤0.05). Conclusion:Aerobic training can protect the heart against Ischemia-Reperfusion injury. It seems that improvement of autophagy balance during IR injury may be involved in exercise-induced cardioprotection against Ischemia-Reperfusion.

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Autophagy suppression by exercise pretreatment and p38 inhibition is neuroprotective in cerebral ischemia

Cited by 29 publications

References 54 publications

Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death

Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders

Preconditioning Effect of High-Intensity Aerobic Training on Myocardial Ischemia-Reperfusion Injury and Beclin-1 Gene Expression in Rats

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