Cannabinoid receptor agonist ACEA promotes myelin recovery after spinal cord injury by regulating IL-33
Journal Title: Journal of Air Force Medical University - Year 2023, Vol 44, Issue 6
Abstract
Objective To investigate the protective effect of activating cannabinoid type 1 receptor (CB1R) agonist ACEA in promoting myelin recovery after spinal cord injury (SCI) in mice, and to clarify the role of interleukin-33 (IL-33) in this effect. Methods SCI modeling was performed on the mice by 10-segment spinothoracic transsection method, and the mice were randomly divided into Sham group, SCI (0, 3, 7, 14 d) + Saline group, SCI (3, 7, 14 d) + ACEA group and SCI 14 d + IL-33 group. The expression levels of myelin basic protein (MBP) and IL-33 at the injured site were determined by Western blotting. The in vitro oxygen-glucose deprivation (OGD) model of oligodendrocyte precursor cells (OPC) was used to simulate SCI and divided into Control group, OGD 6 h group, OGD 6 h + ACEA group and OGD 6 h + IL-33 group. The effect of ACEA on OPC differentiation was observed by immunofluorescence. Results Compared with Sham group, MBP protein decreased significantly (P < 0. 01) and IL-33 protein level increased significantly (P < 0. 01) in the spinal cord of mice after SCI. Administration of ACEA after SCI significantly increased MBP and IL-33 protein levels (P < 0. 05, P < 0. 01); After SCI, the percentage of CC1 cells increased significantly after administration of IL-33 ( P < 0. 01 ) . Compared with the Control group, the proportion of MBP, a marker of OPC differentiation and maturation, decreased significantly (P <0. 01), but the fluorescence intensity of IL-33 in OPC increased significantly (P < 0. 01) after 6 h of OGD. After OGD, administration of ACEA significantly increased the proportion of cells expressing MBP ( P < 0. 05) and the fluorescence intensity of IL-33 ( P < 0. 01) . Administration of IL-33 after OGD significantly enhanced the fluorescence intensity of IL-33 in OPC (P < 0. 05). Conclusion The CB1R agonist ACEA may promote CC1 maturation and myelin recovery in mice after SCI by up-regulating the expression of IL-33 at a late stage.
Authors and Affiliations
TANG Jun, LIU Renhuai, HE Chen, YANG Zhengdong, LIU Huiqing, ZHONG Haixing, SU Binxiao
Keywords
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