Objective

We studied the role of the P2X7 receptor on cognitive dysfunction in a mouse model of schizophrenia.

Methods

An adult mouse model was established by treatment with phencyclidine (PCP), an N-methyl-D-aspartate (NMDA) receptor antagonist. Young mice were divided into three groups: 1) the control (saline-injected) group; 2) experimental 5 mg/kg PCP-injected group; and 3) experimental 10 mg/kg PCP-injected group. The mice were subjected to the open-field and Morris water maze tests at 7 weeks. After intraperitoneal injection of the P2X7 receptor antagonist JNJ-47965567, the behaviour tests were performed again. Samples were taken after testing. The P2X7 receptor protein and mRNA expression levels were detected by immunohistochemistry, Western blotting and PCR.

Results

This study revealed that the infant sub-chronic PCP mice model showed severe spatial learning and memory impairment in the Morris water maze and schizophrenia-like symptoms (hypermotor behaviour) in the open-field test. The P2X7 receptor protein was highly expressed in the sub-chronic PCP mouse model and more highly expressed in the hippocampus than the prefrontal lobe. After the P2X7 receptor was blocked with JNJ-47965567, P2X7 receptor protein and mRNA expression in the frontal lobe were significantly increased, and the spatial memory impairment and hypermotor behaviour induced by PCP were reversed.

Conclusion

PCP-induced cognitive impairment can be significantly improved by antagonizing the P2X7 receptor. Therefore, we believe that the P2X7 receptor plays an important role in the cognition of schizophrenic-like mice.

中文翻译：

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P2X7 受体在亚慢性 PCP 诱导的精神分裂症啮齿动物模型中作为治疗靶点的潜力

客观的

我们研究了 P2X7 受体在精神分裂症小鼠模型中对认知功能障碍的作用。

方法

通过用苯环利定 (PCP)、N-甲基-D-天冬氨酸 (NMDA) 受体拮抗剂处理建立成年小鼠模型。幼鼠分为三组：1）对照组（盐水注射）组；2) 实验性 5 mg/kg PCP 注射组；3) 实验性 10 mg/kg PCP 注射组。小鼠在 7 周时接受旷场和莫里斯水迷宫测试。腹腔注射P2X7受体拮抗剂JNJ-47965567后，再次进行行为测试。测试后取样。采用免疫组化、Western blotting和PCR检测P2X7受体蛋白和mRNA表达水平。

结果

这项研究表明，婴儿亚慢性 PCP 小鼠模型在莫里斯水迷宫中表现出严重的空间学习和记忆障碍，在旷场测试中表现出精神分裂症样症状（运动过度行为）。P2X7 受体蛋白在亚慢性 PCP 小鼠模型中高表达，并且在海马中的表达高于前额叶。JNJ-47965567阻断P2X7受体后，额叶P2X7受体蛋白和mRNA表达明显增加，PCP引起的空间记忆障碍和运动过度行为得到逆转。

结论

通过拮抗 P2X7 受体可以显着改善 PCP 诱导的认知障碍。因此，我们认为P2X7受体在精神分裂症样小鼠的认知中起重要作用。