Strobel Matthew R, Zhou Yuxin, Qiu Liyan, Hofer Aldebaran M, Chen Xuanmao
Department of Molecular, Cellular, and Biomedical Sciences, College of Life Sciences and Agriculture, University of New Hampshire, Durham, NH, 03824, USA.
Department of Surgery, VA Boston Healthcare System, Harvard Medical School, Brigham and Women's Hospital, 1400 VFW Parkway, West Roxbury, MA, 02132, USA.
Sci Rep. 2025 Jan 2;15(1):347. doi: 10.1038/s41598-024-83432-1.
The primary cilium is a hair-like organelle that hosts molecular machinery for various developmental and homeostatic signaling pathways. Its alteration can cause rare ciliopathies such as the Bardet-Biedl and Joubert syndromes, but is also linked to Alzheimer's disease, clinical depression, and autism spectrum disorder. These afflictions are caused by disturbances in a wide variety of genes but a common phenotype amongst them is cognitive impairment. While cilia-mediated neural function has been widely examined in early neurodevelopment, their function in the adult brain is not well understood. To help elucidate the role of cilia in neural activity, we temporally induced the ablation of IFT88, a gene encoding the intraflagellar transport 88 protein which is neccessary for ciliogenesis, in adult mice before performing memory-related behavioral assays and electroencephalogram/electromyogram (EEG/EMG) recordings. Inducible IFT88 KO mice exhibited severe learning deficits in trace fear conditioning and Morris water maze tests. They had strongly affected brainwave activity both under isoflurane induced anesthesia and during normal activity. And additionally, inducible IFT88 KO mice had altered sleep architecture and attenuated phase-amplitude coupling, a process that underlies learning and memory formation. These results highlight the growing significance of primary cilia for healthy neural function in the adult brain.
初级纤毛是一种毛发状细胞器，它承载着用于各种发育和稳态信号通路的分子机制。其改变可导致巴德-比德尔综合征和乔伯特综合征等罕见的纤毛病，但也与阿尔茨海默病、临床抑郁症和自闭症谱系障碍有关。这些疾病是由多种基因的紊乱引起的，但它们之间的一个共同表型是认知障碍。虽然纤毛介导的神经功能在早期神经发育中已得到广泛研究，但其在成人大脑中的功能尚不清楚。为了帮助阐明纤毛在神经活动中的作用，我们在成年小鼠中暂时诱导敲除IFT88（一种编码纤毛发生所必需的鞭毛内运输88蛋白的基因），然后进行与记忆相关的行为分析和脑电图/肌电图（EEG/EMG）记录。可诱导的IFT88基因敲除小鼠在痕迹恐惧条件反射和莫里斯水迷宫测试中表现出严重的学习缺陷。它们在异氟烷诱导的麻醉下和正常活动期间的脑电波活动都受到强烈影响。此外，可诱导的IFT88基因敲除小鼠的睡眠结构发生改变，相位-振幅耦合减弱，而这一过程是学习和记忆形成的基础。这些结果凸显了初级纤毛对成人大脑健康神经功能的重要性日益增加。
