Süleyman Demirel University, Faculty of Medicine, Department of Pharmacology, Isparta, Turkey.
Ondokuz Mayıs University, Faculty of Medicine, Department of Medical Biology, Samsun, Turkey.
Neurosci Lett. 2021 Jun 11;755:135908. doi: 10.1016/j.neulet.2021.135908. Epub 2021 Apr 20.
Decades after identifying cannabinoids and their beneficial effects on Parkinson's disease (PD), many gaps are still missing. Although, CB-dependent actions have been shown as underlying positive effects of cannabinoid treatment, in recent years, another receptor of cannabinoids, CB, emerged as a valuable player in cannabinoid-induced neuroprotection. Remarkably, the effects of CB 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 CB on both α-syn and rotenone-treated SH-SY5Y and C8-D1A cells. ACEA and AM-251 were used as CB 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.
在鉴定大麻素及其对帕金森病（PD）的有益作用几十年后，仍有许多空白。尽管已经表明 CB 依赖性作用是大麻素治疗的潜在积极影响，但近年来，大麻素的另一种受体 CB 在大麻素诱导的神经保护中脱颖而出，成为一个有价值的参与者。值得注意的是，CB 的作用主要与中枢神经系统中的免疫细胞、小胶质细胞和星形胶质细胞有关。然而，氧化应激、α-突触核蛋白的积累和免疫失衡是神经元和神经胶质细胞的重要方面。因此，在这项研究中，我们研究了 CB 对 α-突触核蛋白和鱼藤酮处理的 SH-SY5Y 和 C8-D1A 细胞的影响。ACEA 和 AM-251 被用作 CB 激动剂和拮抗剂。在培养物中测定细胞活力、IL-1β、IL-6、TNF-α 水平和 CD200 表达。我们的结果表明，与 C8-D1A 细胞相比，α-突触核蛋白的预形成纤维形式（pFF）在 SH-SY5Y 细胞中没有引起任何显著变化。鱼藤酮显著增加了两种细胞中 IL-1β、IL-6 和 TNF-α 水平的表达。pFF α-突触核蛋白和鱼藤酮处理导致 CD200 表达降低。令人惊讶的是，ACEA 和 AM-251 都减轻了两种细胞系中鱼藤酮诱导的细胞因子水平升高。虽然 ACEA 可预防 pFF α-突触核蛋白诱导的 C8-D1A 细胞中细胞因子水平升高和 CD200 表达降低，但 AM-251 未能影响 CD200 表达水平。此外，ACEA+AM-251 消除了 ACEA 和 AM-251 对两种细胞系中鱼藤酮和 α-突触核蛋白损伤的保护作用。本研究表明，大麻素受体激动剂减轻了神经元和星形胶质细胞中鱼藤酮和 α-突触核蛋白依赖性炎症。
