Cannabinoid receptor-1 has an effect on CD200 under rotenone and alpha-synuclein induced stress. (11th June 2021)

• Record Type: Journal Article
• Authors: Cankara, Fatma Nihan; Çelik, Zülfinaz Betül; Günaydın, Caner
• Is Part Of: Neuroscience letters. Volume 755(2021)
• Publication Date: 2021-06-11
• Subjects: PD Parkinson's disease -- CB2 cannabinoid receptor-2 -- CB1 cannabinoid receptor-1 -- α-syn alpha-synuclein -- ACEA arachidonyl-2'-chloroethylamide -- IL-1β interleukin-1beta -- IL-6 interleukin-6 -- TNF-α tumor necrosis factor-α -- pFF preformed fibril form -- DMEM/F12 Dulbecco's modified eagle medium/Ham's F12 medium -- FBS fetal bovine serum -- FES fetal horse serum -- dPBS Dulbecco's phosphate-buffered saline -- DMSO dimethyl sulfoxide -- MTT 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyl tetrazolium bromide -- mtCB1 mitochondrial CB1 receptors -- ELISA enzyme-linked immunosorbent assay; Alpha-synuclein -- Rotenone -- Cannabinoid receptor-1 -- ACEA -- AM-251 -- CD200 -- Inflammation; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2021.135908
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Rotenone and pFF α-syn decreases CD200 expression in C8-D1A cells. pFF α-syn failed to affect CD200 expression and pro-inflammatory cytokine release in SH-SY5Y cells. Both CB1 agonism and antagonism protected against rotenone and pFF α-syn insult in SH-SY5Y cells. Only CB1 agonism protected against pFF α-syn insult in C8-D1A cells. Abstract: Decades after identifying cannabinoids and their beneficial effects on Parkinson's disease (PD), many gaps are still missing. Although, CB2 -dependent actions have been shown as underlying positive effects of cannabinoid treatment, in recent years, another receptor of cannabinoids, CB1, emerged as a valuable player in cannabinoid-induced neuroprotection. Remarkably, the effects of CB1 are mainly related to immune cells in the CNS, microglia, and astrocytes. However, oxidative stress, α-syn accumulation, and immune disbalance are essential aspects of both neurons and glial cells. Therefore, in this study, we investigated the effects of the CB1 on both α-syn and rotenone-treated SH-SY5Y and C8-D1A cells. ACEA and AM-251 were used as CB1 agonists and antagonists. Cell viability, IL-1β, IL-6, TNF-α levels, and CD200 expressions were determined in culture mediums. Our results demonstrated that preformed fibril form (pFF) of α-syn did not cause any significant change in SH-SY5Y cells compared to C8-D1A cells. Rotenone significantly increased the expression of IL-1β, IL-6, and TNF-α levels in both cells. pFF α-syn and rotenone treatment caused a decrease in CD200 expression. Surprisingly both ACEA and AM-251 alleviated rotenone-induced increase in cytokine levels in both cell lines. Although ACEA prevented pFF α-syn induced increase in cytokine levels and decrease in CD200 expression in C8-D1A cells, AM-251 failed to affect CD200 expression levels. Additionally, ACEA + AM-251 abolished the protective effects of both ACEA and AM-251 against rotenone and α-syn insults in both cell lines. The current study suggests that cannabinoid receptor agonism alleviates rotenone and α-syn-dependent inflammation in neurons and astrocytes.