The promotive effect of activation of the Akt/mTOR/p70S6K signaling pathway in oligodendrocytes on nerve myelin regeneration in rats with spinal cord injury

被引:6
作者
Ge, Chen [1 ,2 ,3 ]
Liu, Dong [1 ]
Sun, Yongming [1 ]
机构
[1] Soochow Univ, Affiliated Hosp 2, Dept Orthoped Surg, 1055 Sanxiang Rd, Suzhou 215004, Jiangsu, Peoples R China
[2] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Orthoped, Sch Med, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Ruijin Hosp North, Dept Orthoped, Sch Med, Shanghai, Peoples R China
关键词
Akt; mTOR; oligodendrocytes; myelin regeneration; SCI;
D O I
10.1080/02688697.2020.1862056
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Purpose Akt/mTOR/p70S6K signaling pathway promotes motor function recovery after spinal cord injury (SCI) in both neurons and astrocytes. But the role and mechanism of this pathway in oligodendrocytes during nerve repair following SCI has not been researched. This study aimed to investigate the effect and mechanism of this signaling pathway in oligodendrocytes on nerve myelin regeneration and motor function recovery in rats with SCI. Methods After inhibiting or activating this signaling pathway, Western blotting and double immunofluorescence labeling were used to determine the levels of the signaling molecules in this pathway and myelin formation-related proteins in the plane of the thoracic segment of the injured spinal cord. The level of motor function recovery was evaluated and the oligodendrocytes involved in nerve myelin regeneration were studied. Primary oligodendrocytes were isolated and cultured in vitro, then MBP, PLP, and MOG were measured with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results Akt/mTOR/p70S6K signaling pathway was activated after SCI compared with the sham-operated rats, prominently elevated levels of the pathway components were observed in the SC79-treated group. The activation of the signaling pathway significantly increased the expression levels of myelin formation-related proteins, including MBP, PLP, and MOG, and improved the Basso, Beattie, and Bresnahan (BBB) scores in the injured spinal cord. Conversely, rapamycin suppressed the expression of these signaling molecules and reduced the levels of myelin formation-related proteins. Conclusion Akt/mTOR/p70S6K signaling pathway activation can contribute to nerve myelin regeneration and has the potential to improve the regenerative environment and motor function, as well as the potential to promote repair of SCI.
引用
收藏
页码:284 / 292
页数:9
相关论文
共 31 条
  • [1] Mammalian Target of Rapamycin (mTOR) Activation Increases Axonal Growth Capacity of Injured Peripheral Nerves
    Abe, Namiko
    Borson, Steven H.
    Gambello, Michael J.
    Wang, Fan
    Cavalli, Valeria
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (36) : 28034 - 28043
  • [2] Oligodendrocyte Fate after Spinal Cord Injury
    Almad, Akshata
    Sahinkaya, F. Rezan
    McTigue, Dana M.
    [J]. NEUROTHERAPEUTICS, 2011, 8 (02) : 262 - 273
  • [3] Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection
    Basso, DM
    Beattie, MS
    Bresnahan, JC
    [J]. EXPERIMENTAL NEUROLOGY, 1996, 139 (02) : 244 - 256
  • [4] Oligodendrocytes: biology and pathology
    Bradl, Monika
    Lassmann, Hans
    [J]. ACTA NEUROPATHOLOGICA, 2010, 119 (01) : 37 - 53
  • [5] Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway
    Brunet, A
    Datta, SR
    Greenberg, ME
    [J]. CURRENT OPINION IN NEUROBIOLOGY, 2001, 11 (03) : 297 - 305
  • [6] Hydrogen-Rich Saline Protects Against Spinal Cord Injury in Rats
    Chen, Chengwen
    Chen, Qianbo
    Mao, Yanfei
    Xu, Shengming
    Xia, Chunyan
    Shi, Xueyin
    Zhang, John H.
    Yuan, Hongbin
    Sun, Xuejun
    [J]. NEUROCHEMICAL RESEARCH, 2010, 35 (07) : 1111 - 1118
  • [7] PERIPHERAL AXON REGROWTH: NEW MOLECULAR APPROACHES
    Christie, K. J.
    Zochodne, D.
    [J]. NEUROSCIENCE, 2013, 240 : 310 - 324
  • [8] mTOR/S6 Kinase Pathway Contributes to Astrocyte Survival during Ischemia
    Dolores Pastor, Maria
    Garcia-Yebenes, Isaac
    Fradejas, Noelia
    Manuel Perez-Ortiz, Jose
    Mora-Lee, Silvia
    Tranque, Pedro
    Angeles Moro, Maria
    Pende, Mario
    Calvo, Soledad
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (33) : 22067 - 22078
  • [9] Dong Y, 2015, INT J CLIN EXP PATHO, V8, P15871
  • [10] Reactions of oligodendrocytes to spinal cord injury: Cell survival and myelin repair
    Frei, E
    Klusman, I
    Schnell, L
    Schwab, ME
    [J]. EXPERIMENTAL NEUROLOGY, 2000, 163 (02) : 373 - 380