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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)

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Abstract

Treadmill exercise is widely considered an effective strategy for restoration of skilled motor function after spinal cord injury (SCI). However, the specific exercise intensity that optimizes recovery and the underlying mechanistic basis of this recovery remain unclear. To that end, we sought to investigate the effect of different treadmill exercise intensities on cortical mTOR activity, a key regulator of functional recovery following CNS trauma, in an animal model of C5 crush spinal cord injury (SCI). Following injury, animals were subjected to treadmill exercise for 4 consecutive weeks at three different intensities (low intensity [LEI]; moderate intensity [MEI]; and high intensity [HEI]). Motor function recovery was assessed by horizontal ladder test, cylinder rearing test, and electrophysiology, while neurotrophic factors and cortical mechanistic target of rapamycin (mTOR) pathway–related proteins were assessed by Western blotting. The activation of the cortical mTOR pathway and axonal sprouting was evaluated by immunofluorescence and the changes of plasticity in motor cortex neurons were assessed by Golgi staining. In keeping with previous studies, we found that 4 weeks of treadmill training resulted in improved skilled motor function, enhanced nerve conduction capability, increased neuroplasticity, and axonal sprouting. Importantly, we also demonstrated that when compared with the LEI group, MEI and HEI groups demonstrated elevated expression of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), phosphorylated ribosomal S6 protein (p-S6), and protein kinase B (p-Akt), consistent with an intensity-dependent activation of the mTOR pathway and neurotrophic factor expression in the motor cortex. We also observed impaired exercise endurance and higher mortality during training in the HEI group than in the LEI and MEI groups. Collectively, our findings suggest that treadmill exercise following SCI is an effective means of promoting recovery and highlight the importance of the cortical mTOR pathway and neurotrophic factors as mediators of this effect. Importantly, our findings also demonstrate that excessive exercise can be detrimental, suggesting that moderation may be the optimal strategy. These findings provide an important foundation for further investigation of treadmill training as a modality for recovery following spinal cord injury and of the underlying mechanisms.

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Data Availability

All data in the current study are available from the corresponding authors on reasonable request.

References

  1. Kumar R, Lim J, Mekary RA, Rattani A, Dewan MC, Sharif SY, Osorio-Fonseca E, Park KB (2018) Traumatic spinal injury: global epidemiology and worldwide volume. World Neurosurg 113:e345–e363. https://doi.org/10.1016/j.wneu.2018.02.033

    Article  Google Scholar 

  2. Mehrholz J, Thomas S, Elsner B (2017) Treadmill training and body weight support for walking after stroke. Cochrane Database Syst Rev 8(8):Cd002840. https://doi.org/10.1002/14651858.CD002840.pub4

  3. Sandrow-Feinberg HR, Houlé JD (2015) Exercise after spinal cord injury as an agent for neuroprotection, regeneration and rehabilitation. Brain Res 1619:12–21. https://doi.org/10.1016/j.brainres.2015.03.052

    Article  CAS  Google Scholar 

  4. Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, Ferreira CK, Harkema SJ (2018) Recovery of over-ground walking after chronic motor complete spinal cord injury. N Engl J Med 379(13):1244–1250. https://doi.org/10.1056/NEJMoa1803588

    Article  Google Scholar 

  5. Rose DK, Nadeau SE, Wu SS, Tilson JK, Dobkin BH, Pei Q, Duncan PW (2017) Locomotor training and strength and balance exercises for walking recovery after stroke: response to number of training sessions. Phys Ther 97(11):1066–1074. https://doi.org/10.1093/ptj/pzx079

    Article  Google Scholar 

  6. Duncan PW, Sullivan KJ, Behrman AL, Azen SP, Wu SS, Nadeau SE, Dobkin BH, Rose DK, Tilson JK, Cen S, Hayden SK (2011) Body-weight-supported treadmill rehabilitation after stroke. N Engl J Med 364(21):2026–2036. https://doi.org/10.1056/NEJMoa1010790

    Article  CAS  Google Scholar 

  7. Karelina K, Schneiderman K, Shah S, Fitzgerald J, Cruz RV, Oliverio R, Whitehead B, Yang J, Weil ZM (2021) Moderate intensity treadmill exercise increases survival of newborn hippocampal neurons and improves neurobehavioral outcomes after traumatic brain injury. J Neurotrauma 38(13):1858–1869. https://doi.org/10.1089/neu.2020.7389

    Article  Google Scholar 

  8. Chin LM, Keyser RE, Dsurney J, Chan L (2015) Improved cognitive performance following aerobic exercise training in people with traumatic brain injury. Arch Phys Med Rehabil 96(4):754–759. https://doi.org/10.1016/j.apmr.2014.11.009

    Article  Google Scholar 

  9. Rahmati M, Keshvari M, Xie W, Yang G, Jin H, Li H, Chehelcheraghi F, Li Y (2022) Resistance training and Urtica dioica increase neurotrophin levels and improve cognitive function by increasing age in the hippocampus of rats. Biomed Pharmacother 153:113306. https://doi.org/10.1016/j.biopha.2022.113306

    Article  CAS  Google Scholar 

  10. Rahmati M, Keshvari M, Mirnasouri R, Chehelcheraghi F (2021) Exercise and Urtica dioica extract ameliorate hippocampal insulin signaling, oxidative stress, neuroinflammation, and cognitive function in STZ-induced diabetic rats. Biomed Pharmacother 139:111577. https://doi.org/10.1016/j.biopha.2021.111577

    Article  CAS  Google Scholar 

  11. Jung SY, Kim DY, Yune TY, Shin DH, Baek SB, Kim CJ (2014) Treadmill exercise reduces spinal cord injury-induced apoptosis by activating the PI3K/Akt pathway in rats. Exp Ther Med 7(3):587–593. https://doi.org/10.3892/etm.2013.1451

    Article  CAS  Google Scholar 

  12. Leech KA, Hornby TG (2017) High-intensity locomotor exercise increases brain-derived neurotrophic factor in individuals with incomplete spinal cord injury. J Neurotrauma 34(6):1240–1248. https://doi.org/10.1089/neu.2016.4532

    Article  Google Scholar 

  13. Bilchak JN, Caron G, Côté MP (2021) Exercise-induced plasticity in signaling pathways involved in motor recovery after spinal cord injury. Int J Mol Sci 22(9). https://doi.org/10.3390/ijms22094858

  14. Wang H, Liu NK, Zhang YP, Deng L, Lu QB, Shields CB, Walker MJ, Li J, Xu XM (2015) Treadmill training induced lumbar motoneuron dendritic plasticity and behavior recovery in adult rats after a thoracic contusive spinal cord injury. Exp Neurol 271:368–378. https://doi.org/10.1016/j.expneurol.2015.07.004

    Article  Google Scholar 

  15. Keshvari M, Rahmati M, Mirnasouri R, Chehelcheraghi F (2020) Effects of endurance exercise and Urtica dioica on the functional, histological and molecular aspects of the hippocampus in STZ-Induced diabetic rats. J Ethnopharmacol 256:112801. https://doi.org/10.1016/j.jep.2020.112801

    Article  CAS  Google Scholar 

  16. Muir GD, Whishaw IQ (1999) Complete locomotor recovery following corticospinal tract lesions: measurement of ground reaction forces during overground locomotion in rats. Behav Brain Res 103(1):45–53. https://doi.org/10.1016/s0166-4328(99)00018-2

    Article  CAS  Google Scholar 

  17. Hilton BJ, Assinck P, Duncan GJ, Lu D, Lo S, Tetzlaff W (2013) Dorsolateral funiculus lesioning of the mouse cervical spinal cord at C4 but not at C6 results in sustained forelimb motor deficits. J Neurotrauma 30(12):1070–1083. https://doi.org/10.1089/neu.2012.2734

    Article  Google Scholar 

  18. Kanagal SG, Muir GD (2007) Bilateral dorsal funicular lesions alter sensorimotor behaviour in rats. Exp Neurol 205(2):513–524. https://doi.org/10.1016/j.expneurol.2007.03.014

    Article  Google Scholar 

  19. Chen K, Zheng Y, Wei JA, Ouyang H, Huang X, Zhang F, Lai CSW, Ren C, So KF, Zhang L (2019) Exercise training improves motor skill learning via selective activation of mTOR. Sci Adv 5(7):eaaw1888. https://doi.org/10.1126/sciadv.aaw1888

  20. Ferreira JC, Rolim NP, Bartholomeu JB, Gobatto CA, Kokubun E, Brum PC (2007) Maximal lactate steady state in running mice: effect of exercise training. Clin Exp Pharmacol Physiol 34(8):760–765. https://doi.org/10.1111/j.1440-1681.2007.04635.x

    Article  CAS  Google Scholar 

  21. Rahmati M, Kazemi A (2019) Various exercise intensities differentially regulate GAP-43 and CAP-1 expression in the rat hippocampus. Gene 692:185–194. https://doi.org/10.1016/j.gene.2019.01.013

    Article  CAS  Google Scholar 

  22. Vieira RP, Claudino RC, Duarte AC, Santos AB, Perini A, Faria Neto HC, Mauad T, Martins MA, Dolhnikoff M, Carvalho CR (2007) Aerobic exercise decreases chronic allergic lung inflammation and airway remodeling in mice. Am J Respir Crit Care Med 176(9):871–877. https://doi.org/10.1164/rccm.200610-1567OC

    Article  Google Scholar 

  23. Pan L, Tan B, Tang W, Luo M, Liu Y, Yu L, Yin Y (2021) Combining task-based rehabilitative training with PTEN inhibition promotes axon regeneration and upper extremity skilled motor function recovery after cervical spinal cord injury in adult mice. Behav Brain Res 405:113197. https://doi.org/10.1016/j.bbr.2021.113197

    Article  CAS  Google Scholar 

  24. Novikova L, Novikov L, Kellerth JO (1997) Persistent neuronal labeling by retrograde fluorescent tracers: a comparison between Fast Blue, Fluoro-Gold and various dextran conjugates. J Neurosci Methods 74(1):9–15. https://doi.org/10.1016/s0165-0270(97)02227-9

    Article  CAS  Google Scholar 

  25. Gyengesi E, Calabrese E, Sherrier MC, Johnson GA, Paxinos G, Watson C (2014) Semi-automated 3D segmentation of major tracts in the rat brain: comparing DTI with standard histological methods. Brain Struct Funct 219(2):539–550. https://doi.org/10.1007/s00429-013-0516-8

    Article  Google Scholar 

  26. Luo M, Yin Y, Li D, Tang W, Liu Y, Pan L, Yu L, Tan B (2021) Neuronal activity-dependent myelin repair promotes motor function recovery after contusion spinal cord injury. Brain Res Bull 166:73–81. https://doi.org/10.1016/j.brainresbull.2020.11.009

    Article  CAS  Google Scholar 

  27. Sholl A, Uttley AM (1953) Pattern discrimination and the visual cortex. Nature 171(4348):387–388. https://doi.org/10.1038/171387a0

    Article  CAS  Google Scholar 

  28. Sholl DA (1953) Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 87(4):387–406

    CAS  Google Scholar 

  29. Sripetchwandee J, Pipatpiboon N, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2014) DPP-4 inhibitor and PPARγ agonist restore the loss of CA1 dendritic spines in obese insulin-resistant rats. Arch Med Res 45(7):547–552. https://doi.org/10.1016/j.arcmed.2014.09.002

    Article  CAS  Google Scholar 

  30. Jin D, Liu Y, Sun F, Wang X, Liu X, He Z (2015) Restoration of skilled locomotion by sprouting corticospinal axons induced by co-deletion of PTEN and SOCS3. Nat Commun 6:8074. https://doi.org/10.1038/ncomms9074

    Article  CAS  Google Scholar 

  31. Zhang W, Yang B, Weng H, Liu T, Shi L, Yu P, So KF, Qu Y, Zhou L (2019) Wheel running improves motor function and spinal cord plasticity in mice with genetic absence of the corticospinal tract. Front Cell Neurosci 13:106. https://doi.org/10.3389/fncel.2019.00106

    Article  CAS  Google Scholar 

  32. Torres-Espín A, Beaudry E, Fenrich K, Fouad K (2018) Rehabilitative training in animal models of spinal cord injury. J Neurotrauma 35(16):1970–1985. https://doi.org/10.1089/neu.2018.5906

    Article  Google Scholar 

  33. Magnuson DS, Smith RR, Brown EH, Enzmann G, Angeli C, Quesada PM, Burke D (2009) Swimming as a model of task-specific locomotor retraining after spinal cord injury in the rat. Neurorehabil Neural Repair 23(6):535–545. https://doi.org/10.1177/1545968308331147

    Article  Google Scholar 

  34. Van Meeteren NL, Eggers R, Lankhorst AJ, Gispen WH, Hamers FP (2003) Locomotor recovery after spinal cord contusion injury in rats is improved by spontaneous exercise. J Neurotrauma 20(10):1029–1037. https://doi.org/10.1089/089771503770195876

    Article  Google Scholar 

  35. Gallegos C, Carey M, Zheng Y, He X, Cao QL (2020) Reaching and grasping training improves functional recovery after chronic cervical spinal cord injury. Front Cell Neurosci 14:110. https://doi.org/10.3389/fncel.2020.00110

    Article  CAS  Google Scholar 

  36. Lovely RG, Gregor RJ, Roy RR, Edgerton VR (1986) Effects of training on the recovery of full-weight-bearing stepping in the adult spinal cat. Exp Neurol 92(2):421–435. https://doi.org/10.1016/0014-4886(86)90094-4

    Article  CAS  Google Scholar 

  37. Barbeau H, Rossignol S (1987) Recovery of locomotion after chronic spinalization in the adult cat. Brain Res 412(1):84–95. https://doi.org/10.1016/0006-8993(87)91442-9

    Article  CAS  Google Scholar 

  38. Ward PJ, Herrity AN, Harkema SJ, Hubscher CH (2016) Training-induced functional gains following SCI. Neural Plast 2016:4307694. https://doi.org/10.1155/2016/4307694

    Article  CAS  Google Scholar 

  39. Jung SY, Seo TB, Kim DY (2016) Treadmill exercise facilitates recovery of locomotor function through axonal regeneration following spinal cord injury in rats. J Exerc Rehabil 12(4):284–292. https://doi.org/10.12965/jer.1632698.349

    Article  Google Scholar 

  40. Shibata T, Tashiro S, Shinozaki M, Hashimoto S, Matsumoto M, Nakamura M, Okano H, Nagoshi N (2021) Treadmill training based on the overload principle promotes locomotor recovery in a mouse model of chronic spinal cord injury. Exp Neurol 345:113834. https://doi.org/10.1016/j.expneurol.2021.113834

    Article  Google Scholar 

  41. Maier IC, Baumann K, Thallmair M, Weinmann O, Scholl J, Schwab ME (2008) Constraint-induced movement therapy in the adult rat after unilateral corticospinal tract injury. J Neurosci 28(38):9386–9403. https://doi.org/10.1523/jneurosci.1697-08.2008

    Article  CAS  Google Scholar 

  42. Bloom MS, Orthmann-Murphy J, Grinspan JB (2022) Motor learning and physical exercise in adaptive myelination and remyelination. ASN Neuro 14:17590914221097510. https://doi.org/10.1177/17590914221097510

    Article  CAS  Google Scholar 

  43. Goldshmit Y, Lythgo N, Galea MP, Turnley AM (2008) Treadmill training after spinal cord hemisection in mice promotes axonal sprouting and synapse formation and improves motor recovery. J Neurotrauma 25(5):449–465. https://doi.org/10.1089/neu.2007.0392

    Article  Google Scholar 

  44. Onifer SM, Smith GM, Fouad K (2011) Plasticity after spinal cord injury: relevance to recovery and approaches to facilitate it. Neurotherapeutics 8(2):283–293. https://doi.org/10.1007/s13311-011-0034-4

    Article  Google Scholar 

  45. Ploughman M, Granter-Button S, Chernenko G, Attwood Z, Tucker BA, Mearow KM, Corbett D (2007) Exercise intensity influences the temporal profile of growth factors involved in neuronal plasticity following focal ischemia. Brain Res 1150:207–216. https://doi.org/10.1016/j.brainres.2007.02.065

    Article  CAS  Google Scholar 

  46. Lou SJ, Liu JY, Chang H, Chen PJ (2008) Hippocampal neurogenesis and gene expression depend on exercise intensity in juvenile rats. Brain Res 1210:48–55. https://doi.org/10.1016/j.brainres.2008.02.080

    Article  CAS  Google Scholar 

  47. Rojas Vega S, Abel T, Lindschulten R, Hollmann W, Bloch W, Strüder HK (2008) Impact of exercise on neuroplasticity-related proteins in spinal cord injured humans. Neuroscience 153(4):1064–1070. https://doi.org/10.1016/j.neuroscience.2008.03.037

    Article  CAS  Google Scholar 

  48. Camargo GL, de Souza RA, da Silva DB, Garcia JAD, Silveira L Jr (2017) Raman spectral characteristics of neck and head of femur in low-density lipoprotein receptor gene knockout mice submitted to treadmill aerobic training. J Photochem Photobiol B 173:92–98. https://doi.org/10.1016/j.jphotobiol.2017.05.017

    Article  CAS  Google Scholar 

  49. Battistuzzo CR, Rank MM, Flynn JR, Morgan DL, Callister R, Callister RJ, Galea MP (2017) Effects Of treadmill training on hindlimb muscles of spinal cord-injured mice. Muscle Nerve 55(2):232–242. https://doi.org/10.1002/mus.25211

    Article  CAS  Google Scholar 

  50. Torres-Espín A, Forero J, Fenrich KK, Lucas-Osma AM, Krajacic A, Schmidt E, Vavrek R, Raposo P, Bennett DJ, Popovich PG, Fouad K (2018) Eliciting inflammation enables successful rehabilitative training in chronic spinal cord injury. Brain 141(7):1946–1962. https://doi.org/10.1093/brain/awy128

    Article  Google Scholar 

  51. Nees TA, Tappe-Theodor A, Sliwinski C, Motsch M, Rupp R, Kuner R, Weidner N, Blesch A (2016) Early-onset treadmill training reduces mechanical allodynia and modulates calcitonin gene-related peptide fiber density in lamina III/IV in a mouse model of spinal cord contusion injury. Pain 157(3):687–697. https://doi.org/10.1097/j.pain.0000000000000422

    Article  CAS  Google Scholar 

  52. Häger C, Keubler LM, Talbot SR, Biernot S, Weegh N, Buchheister S, Buettner M, Glage S, Bleich A (2018) Running in the wheel: defining individual severity levels in mice. PLoS Biol 16(10):e2006159. https://doi.org/10.1371/journal.pbio.2006159

    Article  CAS  Google Scholar 

  53. Wu Q, Cao Y, Dong C, Wang H, Wang Q, Tong W, Li X, Shan C, Wang T (2016) Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury. PeerJ 4:e2025. https://doi.org/10.7717/peerj.2025

    Article  CAS  Google Scholar 

  54. Beverungen H, Klaszky SC, Klaszky M, Côté MP (2020) Rehabilitation decreases spasticity by restoring chloride homeostasis through the brain-derived neurotrophic factor-KCC2 pathway after spinal cord injury. J Neurotrauma 37(6):846–859. https://doi.org/10.1089/neu.2019.6526

    Article  Google Scholar 

  55. Kleim JA, Chan S, Pringle E, Schallert K, Procaccio V, Jimenez R, Cramer SC (2006) BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat Neurosci 9(6):735–737. https://doi.org/10.1038/nn1699

    Article  CAS  Google Scholar 

  56. Mysoet J, Canu MH, Gillet C, Fourneau J, Garnier C, Bastide B, Dupont E (2017) Reorganization of motor cortex and impairment of motor performance induced by hindlimb unloading are partially reversed by cortical IGF-1 administration. Behav Brain Res 317:434–443. https://doi.org/10.1016/j.bbr.2016.10.005

    Article  CAS  Google Scholar 

  57. Kowiański P, Lietzau G, Czuba E, Waśkow M, Steliga A, Moryś J (2018) BDNF: A key factor with multipotent impact on brain signaling and synaptic plasticity. Cell Mol Neurobiol 38(3):579–593. https://doi.org/10.1007/s10571-017-0510-4

    Article  CAS  Google Scholar 

  58. Hakuno F, Takahashi SI (2018) IGF1 receptor signaling pathways. J Mol Endocrinol 61(1):T69-t86. https://doi.org/10.1530/jme-17-0311

    Article  CAS  Google Scholar 

  59. Watson K, Baar K (2014) mTOR and the health benefits of exercise. Semin Cell Dev Biol 36:130–139. https://doi.org/10.1016/j.semcdb.2014.08.013

    Article  CAS  Google Scholar 

  60. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475(7354):91–95. https://doi.org/10.1038/nature10130

    Article  CAS  Google Scholar 

  61. Dyer AH, Vahdatpour C, Sanfeliu A, Tropea D (2016) The role of Insulin-Like Growth Factor 1 (IGF-1) in brain development, maturation and neuroplasticity. Neuroscience 325:89–99. https://doi.org/10.1016/j.neuroscience.2016.03.056

    Article  CAS  Google Scholar 

  62. Park KK, Liu K, Hu Y, Smith PD, Wang C, Cai B, Xu B, Connolly L, Kramvis I, Sahin M, He Z (2008) Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322(5903):963–966. https://doi.org/10.1126/science.1161566

    Article  CAS  Google Scholar 

  63. Duan X, Qiao M, Bei F, Kim IJ, He Z, Sanes JR (2015) Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling. Neuron 85(6):1244–1256. https://doi.org/10.1016/j.neuron.2015.02.017

    Article  CAS  Google Scholar 

  64. Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, Tedeschi A, Park KK, Jin D, Cai B, Xu B, Connolly L, Steward O, Zheng B, He Z (2010) PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 13(9):1075–1081. https://doi.org/10.1038/nn.2603

    Article  CAS  Google Scholar 

  65. Ge C, Liu D, Sun Y (2020) The promotive effect of activation of the Akt/mTOR/p70S6K signaling pathway in oligodendrocytes on nerve myelin regeneration in rats with spinal cord injury. Br J Neurosurg 1–9. https://doi.org/10.1080/02688697.2020.1862056

  66. Wang ZY, Liu WG, Muharram A, Wu ZY, Lin JH (2014) Neuroprotective effects of autophagy induced by rapamycin in rat acute spinal cord injury model. NeuroImmunoModulation 21(5):257–267. https://doi.org/10.1159/000357382

    Article  CAS  Google Scholar 

  67. Sekiguchi A, Kanno H, Ozawa H, Yamaya S, Itoi E (2012) Rapamycin promotes autophagy and reduces neural tissue damage and locomotor impairment after spinal cord injury in mice. J Neurotrauma 29(5):946–956. https://doi.org/10.1089/neu.2011.1919

    Article  Google Scholar 

  68. Kanno H, Ozawa H, Sekiguchi A, Yamaya S, Tateda S, Yahata K, Itoi E (2012) The role of mTOR signaling pathway in spinal cord injury. Cell Cycle 11(17):3175–3179. https://doi.org/10.4161/cc.21262

    Article  CAS  Google Scholar 

  69. Schwab ME, Bartholdi D (1996) Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev 76(2):319–370. https://doi.org/10.1152/physrev.1996.76.2.319

    Article  CAS  Google Scholar 

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Acknowledgements

The authors sincerely appreciate the experimental platform support of the State Key Laboratory of Trauma, Burns and Combined Injury, Department of Research Institute of Surgery, Daping Hospital, Army Military Medical University.

Funding

Botao Tan and Ying Yin were supported by the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University. This work was supported by the National Natural Science Foundation of China (81702221 and 82002377) and the Natural Science Foundation of Chongqing (cstc2020jcyj-msxm0161, cstc2019jcyj-msxmX0195, and cstc2018jcyjAX0180).

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  1. Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Zuxiong Zhan, Lu Pan, Ying Zhu, Yunhang Wang, Qin Zhao, Lehua Yu, Ying Yin & Botao Tan

  2. State Key Laboratory of Trauma, Burns and Combined Injury, Department of Special War Wound, Daping Hospital, Army Medical University, Chongqing, 400042, China

    Yuan Liu, Sen Li, Haiyan Wang & Ce Yang

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Supervision, funding acquisition, and resources supporting: Lehua Yu, Ce Yang, Yuan Liu, Botao Tan, and Ying Yin. Study design, manuscript preparation and writing: Zuxiong Zhan and Botao Tan. Manuscript review: Botao Tan. Animal experiments, statistical collection, and analysis: Zuxiong Zhan, Ying Zhu, Lu Pan, Yunhang Wang. Experimental technology support: Sen Li and Haiyan Wang. All authors read and approved the final manuscript.

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Zhan, Z., Pan, L., Zhu, Y. et al. 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). Mol Neurobiol 60, 960–978 (2023). https://doi.org/10.1007/s12035-022-03117-6

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