{"title":"小白蛋白阳性中间神经元的Kv1.1通道功能障碍有助于早衰素1/2条件双敲除小鼠的焦虑样行为。","authors":"Guang Yang, Yang Zhao, Chenyi Zhao, Jinglan Yan, Yucen Xia, Kun Li, Yongkang Wu, Xingyu Wang, Meng Zhang, Yongjun Chen, Ying Xu","doi":"10.1186/s13578-025-01422-w","DOIUrl":null,"url":null,"abstract":"<p><p>Anxiety occurs in the early stage of cognitive disorders, which can exacerbate cognitive impairment. However, the pathogenesis of this kind of anxiety remains unclear. In this study, we investigated anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout (PS cDKO) mice, a model of progressive cognitive impairment, using behavioral tests and electrophysiological recordings. Disrupted excitatory/inhibitory (E/I) balance was observed in pyramidal neurons (PNs) of the ventral hippocampus (vHPC) CA1 (vCA1) region of PS cDKO mice. Meanwhile, PV + interneurons showed hypoexcitability, associated with increased outward K<sup>+</sup> currents due to elevated Kv1.1 potassium channel levels. Importantly, genetic or pharmacological inhibition of Kv1.1 restored PV + interneuron activity and reduced anxiety-like behaviors. These findings highlight a role of Kv1.1 in controlling PV + interneuron excitability, suggesting that targeting Kv1.1 in vCA1 PV + interneurons could mitigate anxiety in early-stage cognitive dysfunction.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"89"},"PeriodicalIF":6.2000,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199491/pdf/","citationCount":"0","resultStr":"{\"title\":\"Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice.\",\"authors\":\"Guang Yang, Yang Zhao, Chenyi Zhao, Jinglan Yan, Yucen Xia, Kun Li, Yongkang Wu, Xingyu Wang, Meng Zhang, Yongjun Chen, Ying Xu\",\"doi\":\"10.1186/s13578-025-01422-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Anxiety occurs in the early stage of cognitive disorders, which can exacerbate cognitive impairment. However, the pathogenesis of this kind of anxiety remains unclear. In this study, we investigated anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout (PS cDKO) mice, a model of progressive cognitive impairment, using behavioral tests and electrophysiological recordings. Disrupted excitatory/inhibitory (E/I) balance was observed in pyramidal neurons (PNs) of the ventral hippocampus (vHPC) CA1 (vCA1) region of PS cDKO mice. Meanwhile, PV + interneurons showed hypoexcitability, associated with increased outward K<sup>+</sup> currents due to elevated Kv1.1 potassium channel levels. Importantly, genetic or pharmacological inhibition of Kv1.1 restored PV + interneuron activity and reduced anxiety-like behaviors. These findings highlight a role of Kv1.1 in controlling PV + interneuron excitability, suggesting that targeting Kv1.1 in vCA1 PV + interneurons could mitigate anxiety in early-stage cognitive dysfunction.</p>\",\"PeriodicalId\":49095,\"journal\":{\"name\":\"Cell and Bioscience\",\"volume\":\"15 1\",\"pages\":\"89\"},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2025-06-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199491/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell and Bioscience\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13578-025-01422-w\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell and Bioscience","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13578-025-01422-w","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice.
Anxiety occurs in the early stage of cognitive disorders, which can exacerbate cognitive impairment. However, the pathogenesis of this kind of anxiety remains unclear. In this study, we investigated anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout (PS cDKO) mice, a model of progressive cognitive impairment, using behavioral tests and electrophysiological recordings. Disrupted excitatory/inhibitory (E/I) balance was observed in pyramidal neurons (PNs) of the ventral hippocampus (vHPC) CA1 (vCA1) region of PS cDKO mice. Meanwhile, PV + interneurons showed hypoexcitability, associated with increased outward K+ currents due to elevated Kv1.1 potassium channel levels. Importantly, genetic or pharmacological inhibition of Kv1.1 restored PV + interneuron activity and reduced anxiety-like behaviors. These findings highlight a role of Kv1.1 in controlling PV + interneuron excitability, suggesting that targeting Kv1.1 in vCA1 PV + interneurons could mitigate anxiety in early-stage cognitive dysfunction.
期刊介绍：
Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.
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