浏览全部资源
扫码关注微信
跑台训练对急性高原低氧暴露大鼠海马髓鞘再生及认知功能的影响
Effects of treadmill training on remyelination in hippocampus and cognitive function in rats exposed to acute plateau hypoxia
- 陆军军医大学学报 2024年46卷第8期 页码：786-795
- 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，陆军军医大学(第三军医大学)大坪医院特殊环境战伤防治研究室，创伤与化学中毒全国重点实验室
- 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：创伤、烧伤与复合伤国家重点实验室开放课题(SKLKF20.2112);国家自然科学基金青年科学基金(82002377)
DOI：10.16016/j.2097-0927.202307080
中图分类号： R322.81;R339.4;R339.54收稿：2023-07-12，
修回：2023-10-29，
纸质出版：2024-04-30
- 稿件说明：
移动端阅览
张庆, 刘媛, 罗浩东, 等. 跑台训练对急性高原低氧暴露大鼠海马髓鞘再生及认知功能的影响[J]. 陆军军医大学学报, 2024,46(8):786-795.
Qing ZHANG, Yuan LIU, Haodong LUO, et al. Effects of treadmill training on remyelination in hippocampus and cognitive function in rats exposed to acute plateau hypoxia[J]. Journal of Army Medical University, 2024, 46(8): 786-795.
张庆, 刘媛, 罗浩东, 等. 跑台训练对急性高原低氧暴露大鼠海马髓鞘再生及认知功能的影响[J]. 陆军军医大学学报, 2024,46(8):786-795. DOI： 10.16016/j.2097-0927.202307080.
Qing ZHANG, Yuan LIU, Haodong LUO, et al. Effects of treadmill training on remyelination in hippocampus and cognitive function in rats exposed to acute plateau hypoxia[J]. Journal of Army Medical University, 2024, 46(8): 786-795. DOI： 10.16016/j.2097-0927.202307080.
摘要
目的
2
探讨跑台训练对急性高原低氧暴露大鼠海马髓鞘结构及认知功能的影响。
方法
2
SPF级6~8周龄雌性SD大鼠30只(体质量200~220 g)，6只用于损伤后髓鞘形态观察；其余24只随机分为(
n
=8): 对照组、低压缺氧组和跑台训练组。实验组放入海拔6 000 m的低压氧舱内，连续7 d。对照组动物放入密闭舱室内相同时间而不进行缺氧处理。跑台训练组于造模结束后第2天开始4周的跑台训练。训练结束后对各组大鼠进行旷场和Morris水迷宫实验检测观察大鼠认知功能变化；透射电镜(transmission electron microscopy，TEM)观察海马脱髓鞘改变；免疫荧光染色及Western blot检测海马CA1和CA3区少突胶质细胞转录因子2(oligodendrocyte transcription factor 2，Olig2)、髓鞘碱性蛋白(myelin basic protein，MBP)的表达情况。
结果
2
行为学检测结果显示: 低压缺氧组进入旷场中心区域次数、总路程和路程比及Morris水迷宫穿越平台次数和目标区域路程较对照组减少(
P
＜0.05)，而跑台训练组较低压缺氧组有所增加(
P
＜0.05)。免疫荧光染色显示: 低压缺氧组海马CA1和CA3区单位面积内Olig2阳性细胞数量及MBP的平均荧光强度较对照组明显减少(
P
＜0.05)，而跑台训练组较低压缺氧组有所增加(
P
＜0.05)。Western Blot结果显示: 低压缺氧组海马Olig2和MBP蛋白表达水平较对
照组显著降低(
P
＜0.01)，而跑台训练组较低压缺氧组有所增加(
P
＜0.01)。
结论
2
跑台训练能够促进急性高原低氧暴露大鼠CA1和CA3区少突胶质谱系细胞数量和髓鞘相关蛋白的表达增加，并促进海马髓鞘结构修复，从而改善缺氧导致的焦虑样行为及记忆功能障碍。
Abstract
Objective
2
To determine the effects of treadmill training on the structure of hippocampal myelin and cognitive function in rats exposed to acute plateau hypoxia.
Methods
2
With 30 SPF-grade female SD rats (aged 6-8 weeks
weighing 200-220 g)
6 of them were used for observation of myelin structure after injury
and the remaining 24 rats were randomly divided into control group
hypobaric hypoxia group and treadmill training group (
n
=8). The rats in above experimental groups were placed in a low-pressure oxygen chamber at an altitude of 6 000 m for 7 consecutive days
and the rats of the control group were placed in the confined chamber for the same period without hypoxia. Then
the rats of the treadmill training group received a 4-week treadmill training scheme since the day after hypoxia. Finally
all the rats were tested for cognitive function with open field test (OFT) and Morris water maze (MWM). Transmission electron microscopy (TEM) was used to observe the changes of demyelination in the hippocampus. The expression of oligodendrocyte transcription factor 2 (Olig2) and myelin basic protein (MBP) in the hippocampal CA1 and CA3 regions was measured by immunofluorescence staining and Western blotting.
Results
2
Behavioral tests showed that the number into the central area
total distance
distance ratio in OFT and the number of platform crossings and distance to the target area in MWM were reduced in the hypobaric hypoxia group than the control group (
P
<
0.05)
while these indexes were increased in the treadmill training group than in the hypobaric hypoxia group (
P
<
0.05). Immunofluorescence stain
ing indicated that the number of Olig2 positive cells per unit area and the mean fluorescence intensity of MBP in the CA1 and CA3 regions were significantly lessen in the hypobaric hypoxia group than the control group (
P
<
0.05)
while these indicators were higher in the treadmill training group than the hypobaric hypoxia group (
P
<
0.05). Western blotting displayed that the expression levels of Olig2 and MBP in the hippocampus were obviously lower in the hypobaric hypoxia group than the control group (
P
<
0.01)
while the levels were increased in the treadmill training group than the hypobaric hypoxia group (
P
<
0.01).
Conclusion
2
Treadmill training promotes the number of the oligodendrocyte spectrum cells in CA1 and CA3 regions
enhances the expression of myelin-related proteins and improves myelin repair in hippocampus of hypobaric hypoxia rats
and thereby ameliorates hypoxia-induced anxiety-like behaviors and memory dysfunction.
关键词
Keywords
references
RIMOLDI S F, REXHAJ E, DUPLAIN H, et al . Acute and chronic altitude-induced cognitive dysfunction in children and adolescents[J ] . J Pediatr, 2016, 169: 238-243. DOI: 10.1016/j.jpeds.2015.10.009.
DAVRANCHE K, CASINI L, ARNAL P J, et al . Cognitive functions and cerebral oxygenation changes during acute and prolonged hypoxic exposure[J ] . Physiol Behav, 2016, 164 (Pt A): 189-197. DOI: 10.1016/j.physbeh.2016.06.001.
BAILEY D M. Oxygen and brain death; back from the brink[J]. Exp Physiol, 2019, 104(12): 1769-1779. DOI: 10.1113/ep088005.
DHEER A, JAIN V, KUSHWAH N, et al . Temporal and spatial changes in glial cells during chronic hypobaric hypoxia: role in neurodegeneration[J ] . N euroscience, 2018, 383: 235-246. DOI: 10.1016/j.neuroscience.2018.04.026.
CRISTOBAL C D, LEE H K. Development of myelinating glia: an overview[J]. Glia, 2022, 70(12): 2237-2259. DOI: 10.1002/glia.24238.
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.
CHEN J F, LIU K, HU B, et al . Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer's disease[J ] . Neuron, 2021, 109(14): 2292-2307.e5. DOI: 10.1016/j.neuron.2021.05.012.
WANG J, HE X L, MENG H Y, et al . Robust myelination of regenerated axons induced by combined manipulations of GPR17 and microglia[J ] . Neuron, 2020, 108(5): 876-886.e4. DOI: 10.1016/j.neuron.2020.09.016.
VON BERNHARDI J E, DIMOU L. Oligodendrogenesis is a key process for cognitive performance improvement induced by voluntary physical activity[J]. Glia, 2022, 70(6): 1052-1067. DOI: 10.1002/glia.24155.
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.
SOHRABI P, PARNOW A, JALILI C. Treadmill aerobic training improve beam-walking test, up-regulate expression of main proteins of myelin and myelination in the hippocampus of cuprizone-fed mice[J]. Neurosci Lett, 2023, 792: 136936. DOI: 10.1016/j.neulet.2022.136936.
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.
LU Y J, DONG Y, TUCKER D, et al . Treadmill exercise exerts neuroprotection and regulates microglial polarization and oxidative stress in a streptozotocin-induced rat model of sporadic Alzheimer's disease[J ] . J Alzheimers Dis, 2017, 56(4): 1469-1484. DOI: 10.3233/JAD-160869.
WU C Y, YANG L D, LI Y, et al . Effects of exercise training on anxious-depressive-like behavior in Alzheimer rat[J ] . Med Sci Sports Exerc, 2020, 52(7): 1456-1469. DOI : 10.1249/MSS.0000000000002294.
ZHANG G, ZHOU S M, ZHENG S J, et al . Astragalus on the anti-fatigue effect in hypoxic mice[J ] . Int J Clin Exp Med, 2015, 8(8): 14030-14035.
MAITI P, SINGH S B, MUTHURAJU S, et al . Hypobaric hypoxia damages the hippocampal pyramidal neurons in the rat brain[J ] . Brain Res, 2007, 1175: 1-9. DOI: 10.1016/j.brainres.2007.06.106.
CHEN L, REN S Y, LI R X, et al . Chronic exposure to hypoxia inhibits myelinogenesis and causes motor coordination deficits in adult mice[J ] . Neurosci Bull, 2021, 37(10): 1397-1411. DOI: 10.1007/s12264-021-00745-1.
MCGUIRE S, SHERMAN P, PROFENNA L, et al . White matter hyperintensities on MRI in high-altitude U-2 pilots[J ] . Neurology, 2013, 81(8): 729-735. DOI: 10.1212/WNL.0b013e3182a1ab12.
FRIEDRICH M G, SKORA A, HANCOCK S E, et al . Tau is truncated in five regions of the normal adult human brain[J ] . Int J Mol Sci, 2021, 22(7): 3521. DOI: 10.3390/ijms22073521.
LUKS A M, MCINTOSH S E, GRISSOM C K, et al . Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2014 update[J ] . Wilderness Environ Med, 2014, 25(4 Suppl): S4-S14. DOI: 10.1016/j.wem.2014.06.017.
CHEN K, ZHENG Y H, WEI J A, 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.
TANG J, LIANG X, DOU X Y, et al . Exercise rather than fluoxetine promotes oligodendrocyte differentiation and myelination in the hippocampus in a male mouse model of depression[J ] . Transl Psychiatry, 2021, 11(1): 622. DOI: 10.1038/s41398-021-01747-3.
崔玥, 黄文烨, 孟凡成, 等. 中缝背核5-羟色胺能神经环路在慢性痛及焦虑共病中的研究进展[J]. 空军军医大学学报, 2023, 44(11): 1109-1112, 1117.
CUI Y, HUANG W Y, MENG F C, et al . Research progress of dorsal raphe nucleus serotonergic neural circuit in chronic pain and anxiety comorbidities[J ] . J Air Force Univ, 2023, 44(11): 1109-1112, 1117.
GIBSON E M, PURGER D, MOUNT C W, et al . Neuronal activity promotes oligodendrogenesis and adaptive myelination in the m ammalian brain[J ] . Science, 2014, 344(6183): 1252304. DOI: 10.1126/science.1252304.
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.
BERGLES D E, ROBERTS J D, SOMOGYI P, et al . Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus[J ] . Nature, 2000, 405(6783): 187-191. DOI: 10.1038/35012083.
GAUTIER H O B, EVANS K A, VOLBRACHT K, et al . Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors[J ] . Nat Commun, 2015, 6: 8518. DOI: 10.1038/ncomms9518.
KAPELL H, FAZIO L, DYCKOW J, et al . Neuron-oligodendrocyte potassium shuttling at nodes of Ranvier protects against inflammatory demyelination[J ] . J Clin Invest, 2023, 133(7): e164223. DOI: 10.1172/JCI164223.
MU L W, XIA D D, CAI J J, et al . Treadmill exercise reduces neuroinflammation, glial cell activation and improves synaptic transmission in the prefrontal cortex in 3×tg-AD mice[J ] . Int J Mol Sci, 2022, 23(20): 12655. DOI: 10.3390/ijms232012655.
XING B, BRINK L E, MAERS K, et al . Conditional depletion of GSK3b protects oligodendrocytes from apoptosis and lessens demyelination in the acute cuprizone model[J ] . Glia, 2018, 66(9): 1999-2012. DOI: 10.1002/glia.23453.
AZIM K, BUTT A M. GSK3β negatively regulates oligodendrocyte differentiation and myelination in vivo[J]. Glia, 2011, 59(4): 540-553. DOI: 10.1002/glia.21122.
0
浏览量
231
下载量
1
CSCD
- 网络PDF下载
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 京ICP备09064830号-19
京公网安备11010802024621 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
