跑台训练对成年小鼠脊髓损伤后髓鞘结构修复的影响

苏虹; 潘璐; 朱莹; 王昀杭; 刘媛; 杨策; 李森; 王海燕; 龙在云; 殷樱; 谭波涛

doi:10.16016/j.2097-0927.202207007

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跑台训练对成年小鼠脊髓损伤后髓鞘结构修复的影响

神经科学 | 更新时间：2026-01-09

- 跑台训练对成年小鼠脊髓损伤后髓鞘结构修复的影响
- Effects of treadmill training on myelin structure repair after spinal cord injury in adult mice
- 陆军军医大学学报 2023年45卷第2期页码：111-120
- 作者机构：
  
  1.400010 重庆，重庆医科大学附属第二医院康复医学科
  2.400042 重庆，陆军特色医学中心野战外科研究部特殊环境战伤防治研究室，创伤、烧伤与复合伤国家重点实验室
- 作者简介：
  
  [谭波涛，E-mail：303518@cqmu.edu.cn TAN Botao, E-mail: 303518@cqmu.edu.cn
- 基金信息：
  
  国家自然科学基金青年科学基金(82002377);重庆市自然科学基金面上项目(cstc2019jcyj-msxmX0195);创伤烧伤与复合伤国家重点实验室开放基金资助项目(SKLKF202111)
- DOI：10.16016/j.2097-0927.202207007
  中图分类号： R-332;R455;R651.2
- 收稿：2022-07-02，
  
  修回：2022-09-14，
  
  纸质出版：2023-01-30
- 稿件说明：
移动端阅览
苏虹, 潘璐, 朱莹, 等. 跑台训练对成年小鼠脊髓损伤后髓鞘结构修复的影响[J]. 陆军军医大学学报, 2023,45(2):111-120.

Hong SU, Lu PAN, Ying ZHU, et al. Effects of treadmill training on myelin structure repair after spinal cord injury in adult mice[J]. Journal of Army Medical University, 2023, 45(2): 111-120.
苏虹, 潘璐, 朱莹, 等. 跑台训练对成年小鼠脊髓损伤后髓鞘结构修复的影响[J]. 陆军军医大学学报, 2023,45(2):111-120. DOI： 10.16016/j.2097-0927.202207007.

Hong SU, Lu PAN, Ying ZHU, et al. Effects of treadmill training on myelin structure repair after spinal cord injury in adult mice[J]. Journal of Army Medical University, 2023, 45(2): 111-120. DOI： 10.16016/j.2097-0927.202207007.

摘要

目的

研究跑台训练对小鼠T10脊髓轻度挫伤后背侧皮质脊髓束(dorsal corticospinal tract

dCST)髓鞘结构修复的影响。

方法

实验采用成年C57/BL雌性小鼠。12只用于模型验证; 另30只按随机数字表法分为(

=10): 假手术组(只接受椎板切除)、脊髓损伤(spinal cord injury

SCI)组和跑台训练组[进行单侧(左侧)脊髓打击伤

]

。跑台训练组于术后1周开始进行为期4周的跑台训练(参数: 12 m/min

30 min/次

1次/d

5 d/周)。取材前2周

对各组小鼠进行初级运动皮质(primary motor cortex

M1)注射生物素化葡聚糖胺(biotinylated dextran amine

BDA)以示踪dCST。4周训练结束后进行组织取材。采用免疫荧光染色检测血小板源性生长因子受体α(platelet-derived gr

owth factor receptor α

PDGFRα)、Ki67蛋白、少突胶质细胞转录因子2(oligodendrocyte transcription factor 2

Olig2)、腺瘤性结肠息肉病蛋白(adenomatous polyposis coli protein

APC/CC1)、髓鞘碱性蛋白(myelin basic protein

MBP)表达情况; 透射电镜(transmission electron microscope

TEM)观察左侧dCST区髓鞘化情况; 在伤前、损伤后1周及训练后1、2、4周对各组小鼠进行左后肢运动功能评估(basso mouse scale

BMS)。

结果

免疫荧光染色显示

SCI组左侧dCST区内PDGFRα/Ki67双阳性细胞数量与PDGFRα阳性细胞数量的比值、Olig2/APC/CC1双阳性细胞数量与Olig2阳性细胞数量的比值以及MBP的平均荧光强度较假手术组显著减少(

0.01)

而跑台训练组较SCI组有所增加(

0.01)。TEM结果显示

SCI组左侧dCST区G-ratio较假手术组显著增加(

0.01)

而跑台训练组较SCI组有所降低(

0.01)。在损伤后各个时间点中

跑台训练组的BMS评分有所改善

但与SCI组相比差异无统计学意义。

结论

跑台训练能够促进SCI小鼠左侧dCST区中OPCs增殖、分化和OLs的成熟

增加髓鞘相关蛋白的表达并促进髓鞘结构的修复。

Abstract

Objective

To investigate the effects of treadmill training on the repair of myelin structure of dorsal corticospinal tract (dCST) in mice with T10 spinal cord mild contusion.

Methods

Twelve adult C57/BL female mice were used to construct and verify the model of spinal cord mild contusion

and another 30 mice were randomly divided into 3 groups (

=10): sham group

spinal cord injury (SCI) group

and treadmill training group.The mice of SCI and treadmill training groups were given unilateral (left) spinal cord contusion

while the sham group was given laminectomy only.A 4-week training scheme was conducted for the treadmill training group 1 week after SCI surgery (parameters: 12 m/min

30 min/session

1 time/day

5 d/week).The primary motor cortex (M1) of mice in each group was injected with biotinylated dextran amine (BDA) to trace dCST 2 weeks before sampling

followed by the collection of tissue samples when the 4-week training finished.Then the expression levels of platelet-derived growth factor receptor α(PDGFRα)

Ki67 protein

oligodendrocyte transcription factor 2(Olig2)

adenomatous polyposis coli protein (APC/CC1) and myelin basic protein (MBP) were detected by immunofluorescence assay.Transmission electron microscopy (TEM) was also used to observe the myelination in the left dCST area.Moreover

Basso Mouse Scale (BMS) was performed in each group to evaluate the motor function of left hindlimb before injury

1 week after injury and 1

and 4 weeks after training.

Results

Immunofluorescent labeling showed that the ratio of PDGFRα/Ki67 double positive cells to the total number of PDGFRα positive cells

the ratio of Olig2/APC/CC1 double positive cells to the total number of Olig2 positive cells

as well as the mean fluorescence intensity of MBP in the left dCST area of the SCI group were significantly lower than those of the sham group (

0.01)

while these indexes were higher in the treadmill training group than in the SCI group (

0.01).TEM results indicated that the G-ratio of the left dCST area was elevated in the SCI group (

0.01)

but was reduced greatly in the treadmill training group (

0.01).Finally

the BMS scores were improved in the treadmill group at each detection time point after injury

but there was no significant difference as compared with the SCI group (

0.05).

Conclusion

Treadmill training can facilitate the proliferation and differentiation of oligodendrocytes precursor cells (OPCs)

improve the maturation of oligodendrocytes (OLs) in the left dCST region

and increase the expression of myelin related proteins

thus promoting the repair of myelin structure after SCI in adult mice.

关键词

Keywords

references

FRANKLIN R J M, FFRENCH-CONSTANT C. Regenerating CNS myelin—from mechanisms to experimental medicines[J]. Nat Rev Neurosci, 2017, 18(12): 753-769. DOI: 10.1038/nrn.2017.136.

HESP Z C, GOLDSTEIN E Z, MIRANDA C J, et al . Chronic oligodendrogenesis and remyelination after spinal cord injury in mice and rats[J ] . J Neurosci, 2015, 35(3): 1274-1290. DOI: 10.1523/JNEUROSCI.2568-14.2015.

CRAWFORD A H, TRIPATHI R B, FOERSTER S, et al . Pre-existing mature oligodendrocytes do not contribute to remyelination following toxin-induced spinal cord demyelination[J ] . Am J Pathol, 2016, 186(3): 511-516. DOI: 10.1016/j.ajpath.2015.11.005.

BACMEISTER C M, BARR H J, MCCLAIN C R, et al . Motor learning promotes remyelination via new and surviving oligodendrocytes[J ] . Nat Neurosci, 2020, 23(7): 819-831. DOI: 10.1038/s41593-020-0637-3.

PAN S, CHAN J R. Clinical applications of myelin plasticity for remyelinating therapies in multiple sclerosis[J]. Ann Neurol, 2021, 90(4): 558-567. DOI: 10.1002/ana.26196.

CHEN K, ZHENG Y H, WEI J, et al . Exercise training improves motor skill learning via selective activation of mTOR[J ] . Sci Adv, 2019, 5(7): eaaw1888. DOI: 10.1126/sciadv.aaw1888.

SHAHIDI S H, KORDI M R, RAJABI H, et al . Exercise modulates the levels of growth inhibitor genes before and after multiple sclerosis[J ] . J Neuroimmunol, 2020, 341: 577172. DOI: 10.1016/j.jneuroim.2020.577172.

MANDOLESI G, BULLITTA S, FRESEGNA D, et al . Voluntary running wheel attenuates motor deterioration and brain damage in cuprizone-induced demyelination[J ] . Neurobiol Dis, 2019, 129: 102-117. DOI: 10.1016/j.nbd.2019.05.010.

JENSEN S K, MICHAELS N J, ILYNTSKYY S, et al . Multimodal enhancement of remyelination by exercise with a pivotal role for oligodendroglial PGC1α[J ] . Cell Rep, 2018, 24(12): 3167-3179. DOI: 10.1016/j.celrep.2018.08.060.

詹祖雄, 谭波涛, 王昀杭, 等. 跑台运动对成年脊髓损伤小鼠运动功能及运动皮质mTOR信号通路的影响[J]. 解放军医学杂志, 2022, 47(7): 685-693. DOI: 10.11855/j.issn.0577-7402.2022.07.0685.

ZHAN Z X, TAN B T, WANG Y H, et al . Effects of treadmill exercise on the motor function and mTOR signal pathway in motor cortex of adult mice after spinal cord injury[J ] . Med J Chin PLA, 2022, 47(7): 685-693. DOI: 10.11855/j.issn.0577-7402.2022.07.0685.

SHIN H Y, KIM H, KWON M J, et al . Molecular and cellular changes in the lumbar spinal cord following thoracic injury: regulation by treadmill locomotor training[J ] . PLoS One, 2014, 9(2): e88215. DOI: 10.1371/journal.pone.0088215.

BASSO D M, FISHER L C, ANDERSON A J, et al . Basso Mouse Scale for locomotion detects differen ces in recovery after spinal cord injury in five common mouse strains[J ] . J Neurotrauma, 2006, 23(5): 635-659. DOI: 10.1089/neu.2006.23.635.

ALIZADEH A, DYCK S M, KARIMI-ABDOLREZAEE S. Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms[J]. Front Neurol, 2019, 10: 282. DOI: 10.3389/fneur.2019.00282.

LUO M L, YIN Y, LI D F, et al . Neuronal activity-dependent myelin repair promotes motor function recovery after contusion spinal cord injury[J ] . Brain Res Bull, 2021, 166: 73-81. DOI: 10.1016/j.brainresbull.2020.11.009.

HASSANNEJAD Z, SHAKOURI-MOTLAGH A, MOKHATAB M, et al . Oligodendrogliogenesis and axon remyelination after traumatic spinal cord injuries in animal studies: a systematic review[J ] . Neuroscience, 2019, 402: 37-50. DOI: 10.1016/j.neuroscience.2019.01.019.

KUHLMANN T, MIRON V, CUI Q, et al . Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis[J ] . Brain, 2008, 131(Pt 7): 1749-1758. DOI: 10.1093/brain/awn096.

WEGENER A, DEBOUX C, BACHELIN C, et al . Gain of Olig2 function in oligodendrocyte progenitors promotes remyelination[J ] . Brain, 2015, 138(Pt 1): 120-135. DOI: 10.1093/brain/awu375.

KIM J W, HA K Y, MOLON J N, et al . Bone marrow-derived mesenchymal stem cell transplantation for chronic spinal cord injury in rats[J ] . Spine, 2013, 38(17): E1065-E1074. DOI: 10.1097/brs.0b013e31829839fa.

ZHANG J, BULLER B A, ZHANG Z G, et al . Exosomes derived from bone marrow mesenchymal stromal cells promote remyelination and reduce neuroinflammation in the demyelinating central nervous system[J ] . Exp Neurol, 2022, 347: 113895. DOI: 10.1016/j.expneurol.2021.113895.

LI Q, HOUDAYER T, LIU S, et al . Induced neural activity promotes an oligodendroglia regenerative response in the injured spinal cord and improves motor function after spinal cord injury[J ] . J Neurotrauma, 2017, 34(24): 3351-3361. DOI: 10.1089/neu.2016.4913.

YOON H, KLEVEN A, PAULSEN A, et al . Interplay between exercise and dietary fat modulates myelinogenesis in the central nervous system[J ] . Biochim Biophys Acta, 2016, 1862(4): 545-555. DOI: 10.1016/j.bbadis.2016.01.019.

JIANG T, ZHANG L Y, PAN X N, et al . Physical exercise improves cognitive function together with microglia phenotype modulation and remyelination in chronic cerebral hypoperfusion[J ] . Front Cell Neurosci, 2017, 11: 404. DOI: 10.3389/fncel.2017.00404.

JIANG T, LUO J, PAN X N, et al . Physical exercise modulates the astrocytes polarization, promotes myelin debris clearance and remyelination in chronic cerebral hypoperfusion rats[J ] . Life Sci, 2021, 278: 119526. DOI: 10.1016/j.lfs.2021.119526.

DAVID S, KRONER A. Repertoire of microglial and macrophage responses after spinal cord injury[J]. Nat Rev Neurosci, 2011, 12(7): 388-399. DOI: 10.1038/nrn3053.

OYINBO C A. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade[J]. Acta Neurobiol Exp (Wars), 2011, 71(2): 281-299.

NORRIE B A, NEVETT-DUCHCHERER J M, GORASSINI M A. Reduced functional recovery by delaying motor training after spinal cord injury[J]. J Neurophysiol, 2005, 94(1): 255-264. DOI: 10.1152/jn.00970.2004.

ROLLS A, SHECHTER R, LONDO N A, et al . Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation[J ] . PLoS Med, 2008, 5(8): e171. DOI: 10.1371/journal.pmed.0050171.

WANG H X, LIU N K, ZHANG Y P, et al . Treadmill training induced lumbar motoneuron dendritic plasticity and behavior recovery in adult rats after a thoracic contusive spinal cord injury[J ] . Exp Neurol, 2015, 271: 368-378. DOI: 10.1016/j.expneurol.2015.07.004.

JAMES N D, BARTUS K, GRIST J, et al . Conduction failure following spinal cord injury: functional and anatomical changes from acute to chronic stages[J ] . J Neurosci, 2011, 31(50): 18543-18555. DOI: 10.1523/JNEUROSCI.4306-11.2011.

VONDRAN M W, SINGH H, HONEYWELL J Z, et al . Levels of BDNF impact oligodendrocyte lineage cells following a cuprizone lesion[J ] . J Neurosci, 2011, 31(40): 14182-14190. DOI: 10.1523/JNEUROSCI.6595-10.2011.

MIN J, SINGH S, FITZGERALD-BOCARSLY P, et al . Insulin-like growth factor Ⅰ regulates G2/M progression through mammalian target of rapamycin signaling in oligodendrocyte progenitors[J ] . Glia, 2012, 60(11): 1684-1695. DOI: 10.1002/glia.22387.

KOUTSOUDAKI P N, PAPASTEFANAKI F, STAMATAKIS A, et al . Neural stem/progenitor cells differentiate into oligodendrocytes, reduce inflammation, and ameliorate learning deficits after transplantation in a mouse model of traumatic brain injury[J ] . Glia, 2016, 64(5): 763-779. DOI: 10.1002/glia.22959.

PARK J S, HOLLOSZY J O, KIM K, et al . Exercise training-induced PPARβ increases PGC-1α protein stability and improves insulin-induced glucose uptake in rodent muscles[J ] . Nutrients, 2020, 12(3): 652. DOI: 10.3390/nu12030652.

WRANN C D, WHITE J P, SALOGIANNNIS J, et al . Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway[J ] . Cell Metab, 2013, 18(5): 649-659. DOI: 10.1016/j.cmet.2013.09.008.

CAMACHO A, HUANG J K, DELINT-RAMIREZ I, et al . Peroxisome proliferator-activated receptor gamma-coactivator-1 alpha coordinates sphingolipid metabolism, lipid raft composition and myelin protein synthesis[J ] . Eur J Neurosci, 2013, 38(5): 2672-2683. DOI: 10.1111/ejn.12281.

HASSANNEJAD Z, YOUSEFIFARD M, AZIZI Y, et al . Axonal degeneration and demyelination following traumatic spinal cord injury: a systematic review and meta-analysis[J ] . J Chem Neur oanat, 2019, 97: 9-22. DOI: 10.1016/j.jchemneu.2019.01.009.

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