滨州医学院学报2025，Vol.48Issue(3)：225-230,236,7.DOI:10.19739/j.cnki.issn1001-9510.2025.03.001
NK3R拮抗剂对小鼠认知功能的影响及作用机制
Effect and mechanism of NK3R antagonists on the cognitive function of mice
摘要
Abstract
Objective To investigate the effects of neurokinin 3 receptor(NK3R)antagonist Talnetant,a potential thera-peutic drug for schizophrenia,on cognitive function in mice and its underlying molecular mechanisms.Methods Mice were ran-domly divided into three groups:the control group,group L,and group H).The L and H groups received intraperitoneal injec-tions of Talnetant at 5 mg/kg and 10 mg/kg,respectively,while the control group received vehicle injections at equivalent doses.Behavioral tests,including the novel object recognition test,Y-maze test,and Morris water maze test,were conducted 30 minutes post-injection.Hippocampal protein expression profiles in the control and H groups were analyzed using proteomics,and Western blotting was performed to validate key candidate proteins.Results Compared with the control group,the L group showed a sig-nificant decrease in the recognition index(P＜0.05)without significant difference in the discrimination index,whereas the H group exhibited a marked reduction in both the recognition index(P＜0.0001)and the discrimination index(P＜0.05).Com-pared with the control group,the spontaneous alternation rate and time spent in the novel arm exhibited no significant difference in the L group,whereas the H group displayed decreased spontaneous alternation rate(P＜0.05)and reduced time in the novel arm(P＜0.01).In the Morris water maze test:compared with the control group,the escape latency to locate the platform showed no significant difference in the L group.However,the H group demonstrated prolonged escape latency(P＜0.05)and significantly reduced time spent in the target quadrant(P＜0.001).Proteomic and pathway enrichment analyses revealed86 dif-ferentially expressed proteins(P＜0.05)between the control and H groups,primarily enriched in neurological and synaptic pathways.Western blotting confirmed significant downregulation of neurokinin 3 receptor(NK3R),β-synuclein(Sncb),and G protein-coupled receptor 158(Gpr158)in the H group compared to the control group(P＜0.01).Conclusion Injection of Tal-netant at a dose of 5 mg/kg had mild effects on cognitive function in mice,whereas a dose of 10 mg/kg significantly impacted cognitive function.Talnetant may induce cognitive impairments in mice by downregulating the expression of Sncb and Gpr158 in the hippocampus,thereby affecting synaptic function.关键词
NK3R/Talnetant/认知功能/蛋白质组学Key words
NK3R/Talnetant/cognitive function/proteomics分类
医药卫生引用本文复制引用
顾兆禧,李慧,刘佳慧,李欧飞,杨春华,米佳..NK3R拮抗剂对小鼠认知功能的影响及作用机制[J].滨州医学院学报,2025,48(3):225-230,236,7.基金项目
国家自然科学基金(32170989) （32170989）
