Department of Physiology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.
Department of Biology, Faculty of Science, Erciyes University, Kayseri, Türkiye.
Pharmacol Biochem Behav. 2023 Aug;229:173593. doi: 10.1016/j.pbb.2023.173593. Epub 2023 Jun 28.
Maternal polyinosinic-polycytidylic acid (Poly I:C) exposure leads to an increase in various proinflammatory cytokines and causes schizophrenia-like symptoms in offspring. In recent years, group I metabotropic glutamate receptors (mGluRs) have emerged as a potential target in the pathophysiology of schizophrenia.
The aim of our study was to investigate the behavioral and molecular changes by using the mGlu1 receptor positive allosteric modulator (PAM) agent RO 67-7476, and the negative allosteric modulator (NAM) agent JNJ 16259685 and the mGlu5 receptor PAM agent VU-29, and NAM agent fenobam in the Poly I:C-induced schizophrenia model in rats.
Female Wistar albino rats were treated with Poly I:C on day 14 of gestation after mating. On the postnatal day (PND) 34-35, 56-57 and 83-84, behavioral tests were performed in the male offspring. On the PND84, brain tissue was collected and the level of proinflammatory cytokines was determined by ELISA method.
Poly I:C caused impairments in all behavioral tests and increased the levels of proinflammatory cytokines. While PAM agents caused significant improvements in prepulse inhibition (PPI), novel object recognition (NOR), spontaneous alternation and reference memory tests, they brought the levels of proinflammatory cytokines closer to the control group. NAM agents were ineffective on behavioral tests. It was observed that PAM agents significantly improved Poly I:C-induced disruption in behavioral and molecular analyses.
These results suggest that PAM agents, particularly the mGlu5 receptor VU-29, are also promising and could be a potential target in schizophrenia.
母体多聚肌苷酸多聚胞苷酸（Poly I:C）暴露会导致各种促炎细胞因子增加，并导致后代出现类似精神分裂症的症状。近年来，I 型代谢型谷氨酸受体（mGluRs）已成为精神分裂症病理生理学的潜在靶点。
本研究旨在通过使用 mGlu1 受体正变构调节剂（PAM）剂 RO 67-7476、负变构调节剂（NAM）剂 JNJ 16259685 和 mGlu5 受体 PAM 剂 VU-29 以及 NAM 剂 fenobam，研究聚 I:C 诱导的精神分裂症模型大鼠的行为和分子变化。
雌性 Wistar 白化大鼠在交配后第 14 天接受 Poly I:C 处理。在雄性后代的生后第 34-35 天、56-57 天和 83-84 天进行行为测试。在生后第 84 天，采集脑组织，通过 ELISA 法测定促炎细胞因子水平。
Poly I:C 导致所有行为测试受损，并增加促炎细胞因子水平。而 PAM 剂在预脉冲抑制（PPI）、新物体识别（NOR）、自发交替和参考记忆测试中均有显著改善作用，使促炎细胞因子水平接近对照组。NAM 剂对行为测试无效。研究结果表明，PAM 剂，特别是 mGlu5 受体 VU-29，改善了 Poly I:C 诱导的行为和分子分析障碍。
这些结果表明，PAM 剂，特别是 mGlu5 受体 VU-29，具有潜在的治疗精神分裂症的作用。
