title: Neuroprotective Effect Is Driven Through the Upregulation of CB1 Receptor in Experimental Autoimmune Encephalomyelitis.
abstract: During immuno-mediated demyelinating lesions, endocannabinoid system participates in both inflammatory and neurodegenerative damage through several mechanisms that involve neuronal and immune cells. Here, we constructed lentiviral vector to upregulate CB1 receptor (CB1R) in the lumbar spinal cord 5-6 region and observe the effect of clinical score and possible mechanism on the occurrence and development of experimental autoimmune encephalomyelitis (EAE). The results show that overexpression of CB1R delayed the onset of clinical signs and ameliorated the severity of disease. Overexpression of CB1R significantly inhibited the expression of NF-kB/p65 and TLR-4 as well as levels of IL-1β, IL-6, and TNF-α, followed by a decrease of IL-17 and an increase of IL-10 in the spinal cord of mice. The percentage of M1 marker CD11b(+)CD16/32(+) cells was decreased, while the percentage of M2 marker CD11b(+)CD206(+) and CD11b(+)IL-10(+) cells was elevated in splenic mononuclear cells (MNCs) of mice with overexpression of CB1R. Interestingly, overexpression of CB1R dramatically enhanced the expression of neurotrophic NT-3, BDNF, and GDNF in the spinal cord. These results indicate that local overexpression of CB1R in the spinal cord exhibited neuroprotective effects in EAE, mainly suppressing inflammatory microenvironment and elevating neurotrophic factors, slightly declining IL-1β and IL-17 in the spleen, and increased IL-10 in the brain. Its complexity remains to be carefully considered and further studied in further investigation.
authors.affiliation: Department of Neurology, Xinhua Hospital, Medical College, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhi-Yin
authors.initials: ZY
authors.lastname: Lou
authors.affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Yu
authors.affiliation: Department of Neurology, Xinhua Hospital, Medical College, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurology, Xinhua Hospital, Medical College, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurology, Renji Hospital, Medical College, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Jiang
authors.affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. bgxiao@shmu.edu.cn.
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Xinhua Hospital, Medical College, Shanghai Jiaotong University, Shanghai, China. zhenguoliu2004@aliyun.com.
authors.forename: Zhen-Guo
authors.initials: ZG
authors.lastname: Liu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007378:Interleukins; D016328:NF-kappa B; D020933:Neurotrophin 3; D043884:Receptor, Cannabinoid, CB1; D014409:Tumor Necrosis Factor-alpha
keywords: CB1 receptor; Experimental autoimmune encephalomyelitis; Inflammation; Lentiviral vectors; Neurotrophic factors