Zhou Xingqin, Liu Dong, Zhang Rongjun, Peng Ying, Qin Xiaofeng, Mao Shishi
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Behav Brain Res. 2016 Jul 15;308:217-21. doi: 10.1016/j.bbr.2016.04.034. Epub 2016 Apr 22.
The aim of study was to investigate the effects of pyrroloquinoline quinone (PQQ) combined with d-serine on the modulation of glycine sites in the brain of rats using social recognition test. Rats were divided into seven groups (n=10) and given repeated intraperitoneal (ip) injections of saline, MK-801 (0.5mg/kg), clozapine (1mg/kg), haloperidol (0.1mg/kg), d-serine (0.8g/kg), PQQ (2.0μg/kg), or d-serine (0.4g/kg) combined with PQQ (1.0μg/kg) for seven days. A social recognition test, including assessment of time-dependent memory impairment, was performed. A non-competitive NMDA receptor antagonist, MK-801, significantly impaired social memory, and this impairment was significantly repaired with an atypical antipsychotic (clozapine) but not with a typical antipsychotic (haloperidol). Likewise, d-serine combined with PQQ significantly improved MK-801-disrupted cognition in naïve rats, whereas haloperidol was ineffective. The present results show that the co-agonist NMDA receptor treated with PQQ and d-serine enhances social memory and may be an effective approach for treating the cognitive dysfunction observed in schizophrenic patients. PQQ stimulates glycine modulatory sites by which it may antagonize indirectly by removing glycine from the synaptic cleft or by binding the unsaturated site with d-serine in the brain, providing the insights into future research of central nervous system and drug discovery.
本研究旨在通过社会认知测试，探讨吡咯喹啉醌（PQQ）与D-丝氨酸联合使用对大鼠大脑中甘氨酸位点的调节作用。将大鼠分为七组（每组n = 10），连续7天腹腔注射生理盐水、MK-801（0.5mg/kg）、氯氮平（1mg/kg）、氟哌啶醇（0.1mg/kg）、D-丝氨酸（0.8g/kg）、PQQ（2.0μg/kg）或D-丝氨酸（0.4g/kg）与PQQ（1.0μg/kg）的组合。进行了一项社会认知测试，包括对时间依赖性记忆障碍的评估。非竞争性NMDA受体拮抗剂MK-801显著损害社会记忆，而非典型抗精神病药物（氯氮平）可显著修复这种损害，典型抗精神病药物（氟哌啶醇）则无效。同样，D-丝氨酸与PQQ联合使用可显著改善MK-801对未处理大鼠认知的破坏作用，而氟哌啶醇则无效。目前的结果表明，PQQ和D-丝氨酸共同作用于NMDA受体可增强社会记忆，可能是治疗精神分裂症患者认知功能障碍的有效方法。PQQ刺激甘氨酸调节位点，可能通过从突触间隙去除甘氨酸或在大脑中与D-丝氨酸结合不饱和位点来间接拮抗，为未来中枢神经系统研究和药物发现提供了思路。
