Moderate-Intensity Treadmill Exercise Promotes mTOR-Dependent Motor Cortical Neurotrophic Factor Expression and Functional Recovery in a Murine Model of Crush Spinal Cord Injury (SCI)

Zhan, Zuxiong; Pan, Lu; Zhu, Ying; Wang, Yunhang; Zhao, Qi; Liu, Yuan; Li, Sen; Wang, Haiyan; Yang, Chen; Yu, Lehua; Yin, Ying; Tan, Botao

doi:10.1007/s12035-022-03117-6

Cited by 8 publications

(13 citation statements)

References 68 publications

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“…Vondran et al found that heterozygous BDNF‐deficient mice showed decreased OPCs proliferation and MBP expression after demyelination (VonDran et al, 2011). Additionally, in our previous work, we observed that 4 weeks of treadmill training elevates BDNF levels in the motor cortex of SCI mice, facilitates nerve conduction, enhances neuroplasticity and axonal sprouting (Zhan et al, 2023), and therefore improves skilled motor function. These reports prompted us to conjecture that exercise‐induced PGC1α‐FNDC5/irisin activation may lead to the potentiation of BDNF‐dependent myelin repair and the improvement of functional performance.…”

Section: Discussionmentioning

confidence: 83%

Myelin repair of spinal cord injury in adult mice induced by treadmill training upregulated peroxisome proliferator‐activated receptor gamma coactivator 1 alpha

Su,

Luo,

Wang

et al. 2023

Glia

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Growing evidence has proven the efficacy of physical exercise in remyelination and motor function performance after spinal cord injury (SCI). However, the molecular mechanisms of treadmill training on myelin repair and functional recovery after SCI have not yet been fully studied. Here, we explored the effect of treadmill training on upregulating peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (PGC1α)‐mediated myelin repair and functional recovery in a mouse model of thoracic T10 contusion injury. A 4‐week treadmill training scheme was conducted on mice with SCI. The expression levels of oligodendrogenesis‐related protein and PGC1α were detected by immunofluorescence, RNA fluorescence in situ hybridization and western blotting. Transmission electron microscopy (TEM) was used to observe myelin structure. The Basso Mouse Scale (BMS) and CatWalk automated gait analysis system were used for motor function recovery evaluation. Motor evoked potentials (MEPs) were also identified. In addition, adeno‐associated virus (AAV)‐mediated PGC1α knockdown in OLs was used to further unravel the role of PGC1α in exercise‐induced remyelination. We found that treadmill training boosts oligodendrocyte precursor cells (OPCs) proliferation, potentiates oligodendrocytes (OLs) maturation, and increases myelin‐related protein and myelin sheath thickness, thus impelling myelin repair and hindlimb functional performance as well as the speed and amplitude of nerve conduction after SCI. Additionally, downregulating PGC1α through AAV attenuated these positive effects of treadmill training. Collectively, our results suggest that treadmill training enhances remyelination and functional recovery by upregulating PGC1α, which should provide a step forward in the understanding of the effects of physical exercise on myelin repair.

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Section: Discussionmentioning

confidence: 83%

Myelin repair of spinal cord injury in adult mice induced by treadmill training upregulated peroxisome proliferator‐activated receptor gamma coactivator 1 alpha

Su,

Luo,

Wang

et al. 2023

Glia

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“… 119 Moreover, a study in mice has reported moderate-intensity treadmill exercise leads to increased expression of several factors in the motor cortex of a crushed spinal cord injury, including brain-derived neurotrophic factor, insulin-like growth factor 1, phosphorylated ribosomal S6 protein, and protein kinase B. 120 These studies support the notion that chronic exercise can induce alterations in nutritional factors and protein synthesis that ultimately facilitate neuronal plasticity.…”

Section: Exercise Increases Nutritional Factors and Protein Synthesismentioning

confidence: 83%

Exercise-induced adaptation of neurons in the vertebrate locomotor system

Dai,

Cheng,

et al. 2024

Journal of Sport and Health Science

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“…Papers reported samples ranging from n = 12–65 and consisted of male and female murids (M:F = 3:2) (Sprague–Dawley rats [ 34 , 38 – 42 , 44 , 49 ], Wistar rats [ 22 , 35 , 36 , 45 – 48 ], and mice [ 37 , 43 ]) aged between 2 and 4 months. The studies used animal models with induced SCI resulting in complete SCI by transection [ 22 , 34 , 35 , 48 ], or incomplete SCI by contusion [ 36 , 38 – 41 , 44 , 45 , 47 , 49 ], hemi-Sect.…”

Section: Resultsmentioning

confidence: 99%

“…The studies used animal models with induced SCI resulting in complete SCI by transection [ 22 , 34 , 35 , 48 ], or incomplete SCI by contusion [ 36 , 38 – 41 , 44 , 45 , 47 , 49 ], hemi-Sect. [ 43 ] compression [ 46 ], or crush injury [ 37 ]. One study did not report the type of injury [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

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The effect of early mobilisation (< 14 days) on pathophysiological and functional outcomes in animals with induced spinal cord injury: a systematic review with meta-analysis

Gray,

Shaikh,

Cowley

et al. 2024

BMC Neurosci

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Introduction The optimum time to mobilise (standing, walking) following spinal cord injury (SCI) is unknown but may have implications for patient outcomes. There are no high-quality experimental studies that examine this issue, with a paucity of guidance for clinicians. Pre-clinical studies lead research in this field and can contribute to knowledge and support future clinical practice. Objective: to evaluate the effect of early compared to no mobilisation on pathophysiological and functional outcomes in animals with induced SCI. Methods A systematic review with meta-analysis was conducted by searching pre-clinical literature in MEDLINE (PubMed), Embase (Ovid), Web of Science, OpenGrey, and EThOS (June 2023). Studies were included of any research method giving numerical results comparing pathophysiological and functional outcomes in rats and mice mobilised within 14-days of induced SCI to those that did not mobilise. Data were synthesised using random-effects meta-analyses. The quality of the evidence was assessed using the CAMARADES checklist. The certainty of findings was reported using the GRADE approach. This study is registered on PROSPERO (CRD42023437494). Results Seventeen studies met the inclusion criteria. Outcomes found that Brain Derived Neurotrophic Factor levels were greater in those that initiated mobilisation within 14-days of SCI compared to the groups that did not. Mobilisation initiated within 14-days of SCI was also associated with statistically significant functional gains: (Basso, Beattie and Bresnahan locomotor rating score (BBB) = 2.13(0–21), CI 1.43, 2.84, Ladder Rung Walking Task = − 12.38(0–100), CI 20.01, − 4.76). Meta-analysis identified the greatest functional gains when mobilisation was initiated within 3 days of SCI (BBB = 3.00, CI 2.31–3.69, p < 0.001), or when delivered at low intensity (BBB = 2.88, CI 2.03–3.70, p < 0.001). Confidence in the findings from this review was low to moderate due to the risk of bias and mixed methodological quality. Conclusion Mobilisation instigated within 14-days of injury, may be an effective way of improving functional outcomes in animal models following SCI, with delays potentially detrimental to recovery. Outcomes from this study support further research in this field to guide future clinical practice.

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Moderate-Intensity Treadmill Exercise Promotes mTOR-Dependent Motor Cortical Neurotrophic Factor Expression and Functional Recovery in a Murine Model of Crush Spinal Cord Injury (SCI)

Cited by 8 publications

References 68 publications

Myelin repair of spinal cord injury in adult mice induced by treadmill training upregulated peroxisome proliferator‐activated receptor gamma coactivator 1 alpha

Myelin repair of spinal cord injury in adult mice induced by treadmill training upregulated peroxisome proliferator‐activated receptor gamma coactivator 1 alpha

Exercise-induced adaptation of neurons in the vertebrate locomotor system

The effect of early mobilisation (< 14 days) on pathophysiological and functional outcomes in animals with induced spinal cord injury: a systematic review with meta-analysis

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