British journal of neurosurgery · 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.
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Ge Chen, Liu Dong, Sun Yongming
Аннотация
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.
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.