Treadmill exercise activates ATF3 and ERK1/2 downstream molecules to facilitate axonal regrowth after sciatic nerve injury

Kim, Jieun; Cho, Yeong-Hyun; Seo, Tae-Beom

doi:10.12965/jer.2040188.094

Cited by 10 publications

(10 citation statements)

References 37 publications

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“…Previous studies reporting on nerve regeneration and regular exercise suggested that that neurotrophin 4/5 and BDNF were required for the early stage of regeneration axons in peripheral nerves, and they were continuously increased for a 4weeks treadmill exercise after SNI ( English et al, 2005 ). In addition, Kim et al (2020) investigated that low-intensity treadmill exercise upregulated expression level of GAP-43 in the injured axons and ipsilateral DRG after SNI. These findings in previous studies support our findings that regular treadmill walking might be a valid therapeutic method for facilitating axonal regrowth in the injured sciatic nerve.…”

Section: Discussionmentioning

confidence: 99%

The timing point of exercise intervention regulates neuropathic pain-related molecules in the ipsilateral dorsal root ganglion neurons after sciatic nerve injury

Cho¹,

Seo²

2022

J Exerc Rehabil

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The purpose of this study was to determine whether the timing of treadmill exercise application can control expression levels of neuropathic pain- and regeneration-related proteins in the ipsilateral lumbar 4 (L4) to 6 (L6) dorsal root ganglion cells (DRG) after sciatic nerve injury (SNI). The experimental rats were randomly divided into five groups: the normal control, SNI+sedentary (IS), exercise+SNI (EI), SNI+exercise (IE), exercise+SNI+exercise (EIE) groups. The rats in exercise groups performed treadmill exercise at a speed of 8 m/min for 30 min once a day during 14 days before and/or after SNI. For investigating the expression of specific neuropathic pain and regeneration-related proteins in DRG, we prepared L4 to L6 DRG in the ipsilateral side. In the quantitative analysis, growth associated protein 43 (GAP-43) and brain-derived neurotrophic factor levels were further increased in the ipsilateral DRG at all treadmill exercise groups than those in IS group. In the histological findings, GAP-43 was qualitatively increased IE and EIE groups than IS group at DRG. Wnt3a and β-catenin were dramatically downregulated in EIE and IE groups than IS groups. In addition, nuclear factor kappa-light-chain-enhancer of activated B cells and tumor necrosis factor-α were significantly decreased in IE and EIE groups than IS group in the ipsilateral DRG. Our findings suggested novel information that regular low-intensity exercise before and/or after SNI might be a therapeutic and preventive approaches for relieving neuropathic pain and improving axonal elongation after peripheral nerve injury.

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Section: Discussionmentioning

confidence: 99%

The timing point of exercise intervention regulates neuropathic pain-related molecules in the ipsilateral dorsal root ganglion neurons after sciatic nerve injury

Cho¹,

Seo²

2022

J Exerc Rehabil

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“…In addition, there are no significant differences TEX and TEX+BMSC groups. In previous studies, GAP-43 started to be expressed from the early phase of the sciatic nerve regeneration and treadmill exercise continuously increased from 1 day to 2 weeks after SNI (Kim et al, 2020;Seo et al, 2009). BMSC-dervied extracellular vesicles treatment also promoted the functional recovery and nerve regeneration after SNI through upregulation of GAP-43 protein (Ma et al, 2017).…”

Section: Discussionmentioning

confidence: 89%

Effect of treadmill exercise combined with bone marrow stromal cell transplantation on atrophy-related signaling pathway in the denervated soleus muscle

Cho¹,

Seo²

2021

J Exerc Rehabil

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The purpose of this study was to investigate whether combination of low-intensity exercise with bone marrow stromal cell (BMSC) transplantation could regulate protein kinas B (Akt)- mammalian target of rapamycin (mTOR) and Wnt3a-β-catenin signaling pathways for prevention of soleus muscle atrophy after sciatic nerve injury (SNI). The experimental rats divided into 5 groups (n= 10): normal control group, SNI+sedentary group (SED), SNI+low-intensity treadmill exercise group (TEX), SNI+BMSC transplantation group (BMSC), SNI+TEX+BMSC transplantation group (TEX+BMSC). Sciatic nerve crush injury was applied into the middle of thigh twice for 1 min and 30 sec at interval. Low-intensity treadmill exercise was comprised of walking at a speed of 4 to 8 m/min for 30 min once a day. cultured BMSC at a density of 5× 106 in 50-μL phosphate-buffered saline was injected into the distal portion of the injured sciatic nerves. TEX+BMSC group dramatically upregulated expression levels of growth-associated protein-43 in the injured sciatic nerve at 2 weeks postinjury. Also, although Akt and mTOR signaling pathway significantly increased in TEX and BMSC groups than SED group, TEX+BMSC group showed more potent increment on this signaling in soleus muscle after SNI. Lastly, Wnt3a and the nuclear translocation of β-catenin and nuclear factor-kappa B in soleus were increased by SNI, but TEX+BMSC group significantly downregulated activity of this signaling pathway in the nuclear cell lysate of soleus muscle. Present findings provide new information that combination of low-intensity treadmill exercise might be effective therapeutic approach on restriction of soleus muscle atrophy after peripheral nerve injury.

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“…Moreover, exercise upregulates ATF3 transcription in skeletal muscle after exercise ( Fernández-Verdejo et al, 2017 ). Treadmill exercise can promote sciatic nerve injury regeneration through ATF3 upregulation ( Kim et al, 2020 ). In contrast, silencing of the ATF3 family gene can inhibit exercise-induced angiogenesis ( Fan et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Exercise Modifies the Transcriptional Regulatory Features of Monocytes in Alzheimer’s Patients: A Multi-Omics Integration Analysis Based on Single Cell Technology

Chen

Sun

Luo

et al. 2022

Front. Aging Neurosci.

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Monocytes have been reported to be important mediators of the protective effect of exercise against the development of Alzheimer’s disease (AD). This study aims explored the mechanism by which monocytes achieve this. Using single cell transcriptome analysis, results showed that CD14 + and CD16 + monocytes interacted with other cells in the circulating blood. TNF, CCR1, APP, and AREG, the key ligand-receptor-related genes, were found to be differentially expressed between exercise-treated and AD patients. The SCENIC analysis was performed to identify individual clusters of the key transcription factors (TFs). Nine clusters (M1-M9) were obtained from the co-expression network. Among the identified TFs, MAFB, HES4, and FOSL1 were found to be differentially expressed in AD. Moreover, the M4 cluster to which MAFB, HES4, and FOSL1 belonged was defined as the signature cluster for AD phenotype. Differential analysis by bulkRNA-seq revealed that the expression of TNF, CCR1, and APP were all upregulated after exercise (p < 0.05). And ATF3, MAFB, HES4, and KLF4 that were identified in M4 clusters may be the TFs that regulate TNF, CCR1, and APP in exercise prescription. After that, APP, CCR1, TNF, ATF3, KLF4, HES4, and MAFB formed a regulatory network in the ERADMT gene set, and all of them were mechanistically linked. The ERADMT gene set has been found to be a potential risk marker for the development of AD and can be used as an indicator of compliance to exercise therapy in AD patients. Using single-cell integration analysis, a network of exercise-regulating TFs in monocytes was constructed for AD disease. The constructed network reveals the mechanism by which exercise regulated monocytes to confer therapeutic benefits against AD and its complications. However, this study, as a bioinformatic research, requires further experimental validation.

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Treadmill exercise activates ATF3 and ERK1/2 downstream molecules to facilitate axonal regrowth after sciatic nerve injury

Cited by 10 publications

References 37 publications

The timing point of exercise intervention regulates neuropathic pain-related molecules in the ipsilateral dorsal root ganglion neurons after sciatic nerve injury

The timing point of exercise intervention regulates neuropathic pain-related molecules in the ipsilateral dorsal root ganglion neurons after sciatic nerve injury

Effect of treadmill exercise combined with bone marrow stromal cell transplantation on atrophy-related signaling pathway in the denervated soleus muscle

Exercise Modifies the Transcriptional Regulatory Features of Monocytes in Alzheimer’s Patients: A Multi-Omics Integration Analysis Based on Single Cell Technology

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