期刊
BRAIN RESEARCH BULLETIN
卷 166, 期 -, 页码 73-81出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2020.11.009
关键词
SCI; Neuronal activity; DREADDs; Remyelination; Oligodendrocyte lineage cells (OLs); motor function
资金
- National Natural Science Foundation of China [82002377, 81702221]
- Natural Science Foundation of Chongqing [cstc2019jcyjmsxmX0195, cstc2018jcyjAX0180]
- Natural Science Foundation of Yuzhong, Chongqing [20180121]
- State Key Laboratory of Trauma, Burns and Combined Injury. Department of Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China
The bidirectional regulation of neuronal activity can effectively modulate the development of oligodendrocyte lineage cells and the remyelination process, ultimately affecting motor function recovery. Therefore, manipulation of neuronal activity is a promising avenue for the treatment of demyelination diseases in the central nervous system.
An increasing number of studies connect neuronal activity with developmental myelination but how neuronal activity regulates remyelination has not been clarified. In this study, we induced the demyelination of the dorsal corticospinal tract (dCST) by a mild contusion spinal cord injury (SCI) on the T10 segment, and manipulated the neuronal activity of the primary motor cortex (M1) using chemogenetic viruses to induce activity and to suppress it. We found that oligodendrocyte precursor cell (OPC) proliferation and oligodendrocyte maturity following remyelination was strengthened after 4-week of neuronal activity stimulation. Furthermore, hindlimb motor function was also found to be improved. Vice versa, suppression of neuronal activity attenuated these effects. These results indicate that bidirectional regulation of neuronal activity can effectively modulate the development of oligodendrocyte lineage cells and the remyelination process. Neuronal activity supports the proliferation of OPCs, improves oligodendrocyte maturation and amplifies the axonal remyelination process, even though leads to better motor function recovery. Manipulation of neuronal activity in a non-invasive manner is therefore a promising avenue for exploration towards the treatment of central nervous system (CNS) demyelination diseases.
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