近日，陆军军医大学范晓棠课题组的研究认为UQCRC1表达下调通过破坏齿状回纤毛导致认知能力下降。2025年11月3日出版的《神经科学通报》杂志发表了这项成果。

泛醇细胞色素c还原酶核心蛋白I （UQCRC1）是复合物III的一个重要亚基，对其组装至关重要。UQCRC1表达减少会损害小鼠的记忆和空间学习能力，但其机制尚不清楚。本研究发现，UQCRC1表达的减少导致海马依赖性认知的显著损伤，这与UQCRC1和齿状回（DG）内突触蛋白的显著减少相关。海马体的RNA测序分析显示纤毛减少，这被认为是导致这些认知缺陷的关键因素。值得注意的是，Ttbk2在DG中的过表达恢复了纤毛功能并减轻了认知障碍。

此外，体内电生理实验表明，Uqcrc1^+/-小鼠海马DG中存在θ和γ节律和宽波神经元间反应性，并可通过Ttbk2过表达而获救。这些研究结果表明，UQCRC1表达下调可能由于纤毛损伤导致神经振荡和宽波中间神经元功能受损，从而导致认知能力下降。

附：英文原文

Title: Downregulation of UQCRC1 Expression Leads to Cognitive Decline by Disrupting the Cilia in the Dentate Gyrus

Author: Zhang, Jing, Liu, Tianyao, Long, Zonghong, Wu, Zuoxi, Luo, Jing, Bai, Fuhai, Zhou, Lianyu, Gong, Hong, Gong, Meifeng, Li, Hong, Fan, Xiaotang

Issue&Volume: 2025-11-03

Abstract: Ubiquinol cytochrome c reductase core protein I (UQCRC1) is a crucial subunit of Complex III, essential for its assembly. Reduced UQCRC1 expression impairs memory and spatial learning in mice, though the mechanisms are unclear. This study found that diminished UQCRC1 expression resulted in significant impairments in hippocampus-dependent cognition, which correlated with a notable decrease in UQCRC1 and synaptic proteins within the dentate gyrus (DG). RNA sequencing analysis of the hippocampus revealed a reduction in cilia, identified as a critical factor contributing to these cognitive deficits. Significantly, the overexpression of Ttbk2 in the DG restored ciliary function and mitigated cognitive impairments. Additionally, in vivo electrophysiological experiments demonstrated that theta and gamma rhythms and wide-wave interneuron reactivity in the hippocampus DG were present in Uqcrc1+/- mice and could be rescued through Ttbk2 overexpression. These findings suggest that the downregulation of UQCRC1 expression contributes to cognitive decline by impairing neural oscillations and the functionality of wide-wave interneurons, likely due to ciliary damage.

DOI: 10.1007/s12264-025-01532-y

Source: https://link.springer.com/article/10.1007/s12264-025-01532-y