Our previous study showed that dizocilpine (MK-801) induced schizophrenia-like behavior in rats, enhanced GFAP expression, and activated primary cultured hippocampal astrocytes. Astrocytes play an essential role in neuroinflammation and contribute to the crosstalk that generates chronic neuro-inflammation in neurological diseases. However, the effects of MK-801 treatment on astrocytic neuroinflammatory responses and its mechanism of action have not been studied in detail. To address this issue, IL1β, IL6, TNFα and IL10 expression and secretion levels were evaluated in hippocampal astrocytes in response to MK-801 for 24 h by ELISA and real-time PCR, with and without pretreatment of either the ERK1/2 inhibitor, PD98059 or the PI3K inhibitor, LY294002. Cell apoptosis, viability, and proliferation were also examined. MK-801 treatment did not induce hippocampal astrocytes apoptosis or proliferation, however, MK-801 enhanced astrocytes viability. Additionally, the expression and secretion levels of IL1β, IL6 and TNFα were elevated, but that of IL10 was decreased, in which ERK1/2 and PI3K signals were involved. These findings suggest that hippocampal astrocytes may regulate the expressions of inflammatory cytokines through ERK1/2 and PI3K signaling pathway to participate in the pathogenesis of schizophrenia.

中文翻译：

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通过 ERK1/2 和 PI3K 信号响应 MK-801 改变原代海马星形胶质细胞中炎性细胞因子的表达

我们之前的研究表明，地佐西平 (MK-801) 在大鼠中诱导精神分裂症样行为，增强 GFAP 表达，并激活原代培养的海马星形胶质细胞。星形胶质细胞在神经炎症中发挥重要作用，并有助于在神经系统疾病中产生慢性神经炎症的串扰。然而，尚未详细研究 MK-801 治疗对星形胶质细胞神经炎症反应的影响及其作用机制。为了解决这个问题，通过 ELISA 和实时 PCR 评估海马星形胶质细胞中 IL1β、IL6、TNFα 和 IL10 的表达和分泌水平，以响应 MK-801 24 小时，无论是否预处理 ERK1/2 抑制剂， PD98059 或 PI3K 抑制剂 LY294002。还检查了细胞凋亡、活力和增殖。MK-801 治疗不诱导海马星形胶质细胞凋亡或增殖，然而，MK-801 增强了星形胶质细胞的活力。此外，IL1β、IL6和TNFα的表达和分泌水平升高，而IL10的表达和分泌水平降低，其中涉及ERK1/2和PI3K信号。这些发现提示海马星形胶质细胞可能通过ERK1/2和PI3K信号通路调节炎性细胞因子的表达参与精神分裂症的发病机制。