Serotonin exerts anti-inflammatory, antioxidant and antiapoptotic effects through 5-HT7 receptors. The present study determined the role of 5-HT7 receptors in glutamate-induced neurotoxicity by using human SH-SY5Y neuroblastoma cells. The cells were pretreated with different concentrations of 5-HT7 receptor agonist LP44 and antagonist SB269970 for 60 min, followed by treatment with glutamate. Cell proliferation was measured using xCELLigence system. Treatment with all the concentrations of LP44 significantly protected the cells from the toxic effects of glutamate after 24, 48 and 72 h. Although 5-HT7 receptor expression was significantly upregulated in glutamate-treated cells, it was downregulated in LP44-pretreated cells. Furthermore, LP44 treatment significantly decreased malondialdehyde levels and increased superoxide dismutase activities and glutathione levels. Moreover, LP44 treatment significantly decreased tumor necrosis factor alpha (TNF-α) levels and inhibited caspase 3 and caspase 9 mRNA expression. In contrast, SB269970 treatment exerted an insignificant effect on oxidative stress, inflammation and apoptosis. These findings suggest that exogenous stimulation of the 5-HT7 receptors may be protective in glutamate-induced neurotoxicity and that 5-HT7 receptor agonists can be used as therapeutic agents for preventing glutamate-induced neurological disorders.

中文翻译：

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5-HT7受体激活通过抗氧化和抗凋亡途径对谷氨酸诱导的人神经母细胞瘤SH-SY5Y细胞神经毒性的保护作用。

血清素通过5-HT7受体发挥抗炎，抗氧化和抗凋亡作用。本研究通过使用人类SH-SY5Y神经母细胞瘤细胞确定了5-HT7受体在谷氨酸诱导的神经毒性中的作用。用不同浓度的5-HT 7受体激动剂LP44和拮抗剂SB269970预处理细胞60分钟，然后用谷氨酸处理。使用xCELLigence系统测量细胞增殖。在24、48和72小时后，用所有浓度的LP44处理均能显着保护细胞免受谷氨酸的毒性作用。尽管5-HT7受体的表达在谷氨酸处理的细胞中显着上调，但在LP44预处理的细胞中却下调。此外，LP44处理可显着降低丙二醛水平并增加超氧化物歧化酶活性和谷胱甘肽水平。此外，LP44处理可显着降低肿瘤坏死因子α（TNF-α）水平，并抑制caspase 3和caspase 9 mRNA表达。相比之下，SB269970处理对氧化应激，炎症和细胞凋亡作用不明显。这些发现表明，对5-HT 7受体的外源刺激在谷氨酸诱导的神经毒性中可能是保护性的，并且5-HT 7受体激动剂可以用作预防谷氨酸诱导的神经系统疾病的治疗剂。SB269970处理对氧化应激，炎症和细胞凋亡影响不大。这些发现表明，对5-HT 7受体的外源刺激在谷氨酸诱导的神经毒性中可能是保护性的，并且5-HT 7受体激动剂可以用作预防谷氨酸诱导的神经系统疾病的治疗剂。SB269970处理对氧化应激，炎症和细胞凋亡影响不大。这些发现表明，对5-HT 7受体的外源刺激在谷氨酸诱导的神经毒性中可能是保护性的，并且5-HT 7受体激动剂可以用作预防谷氨酸诱导的神经系统疾病的治疗剂。