Scholarlink

<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>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月25日

查看全文
  • Guang Yang,
  • Yang Zhao,
  • Chenyi Zhao,
  • Jinglan Yan,
  • Yucen Xia,
  • Kun Li,
  • Yongkang Wu,
  • Xingyu Wang,
  • Meng Zhang,
  • Yongjun Chen,
  • Ying Xu

摘要

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.