Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns

Abstract 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,...

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Main Authors: Matthew R. Strobel, Yuxin Zhou, Liyan Qiu, Aldebaran M. Hofer, Xuanmao Chen
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-83432-1
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author Matthew R. Strobel
Yuxin Zhou
Liyan Qiu
Aldebaran M. Hofer
Xuanmao Chen
author_facet Matthew R. Strobel
Yuxin Zhou
Liyan Qiu
Aldebaran M. Hofer
Xuanmao Chen
author_sort Matthew R. Strobel
collection DOAJ
description Abstract 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.
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spelling doaj-art-61d169074d3a49a6a59e9d139aa6f6a22025-01-05T12:18:30ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-024-83432-1Temporal ablation of the ciliary protein IFT88 alters normal brainwave patternsMatthew R. Strobel0Yuxin Zhou1Liyan Qiu2Aldebaran M. Hofer3Xuanmao Chen4Department of Molecular, Cellular, and Biomedical Sciences, College of Life Sciences and Agriculture, University of New HampshireDepartment of Molecular, Cellular, and Biomedical Sciences, College of Life Sciences and Agriculture, University of New HampshireDepartment of Molecular, Cellular, and Biomedical Sciences, College of Life Sciences and Agriculture, University of New HampshireDepartment of Surgery, VA Boston Healthcare System, Harvard Medical School, Brigham and Women’s HospitalDepartment of Molecular, Cellular, and Biomedical Sciences, College of Life Sciences and Agriculture, University of New HampshireAbstract 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.https://doi.org/10.1038/s41598-024-83432-1Primary ciliaEEG/EMGSleep analysisCross-frequency coupling (CFC)Phase-amplitude couplingHippocampal memory formation
spellingShingle Matthew R. Strobel
Yuxin Zhou
Liyan Qiu
Aldebaran M. Hofer
Xuanmao Chen
Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns
Scientific Reports
Primary cilia
EEG/EMG
Sleep analysis
Cross-frequency coupling (CFC)
Phase-amplitude coupling
Hippocampal memory formation
title Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns
title_full Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns
title_fullStr Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns
title_full_unstemmed Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns
title_short Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns
title_sort temporal ablation of the ciliary protein ift88 alters normal brainwave patterns
topic Primary cilia
EEG/EMG
Sleep analysis
Cross-frequency coupling (CFC)
Phase-amplitude coupling
Hippocampal memory formation
url https://doi.org/10.1038/s41598-024-83432-1
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AT liyanqiu temporalablationoftheciliaryproteinift88altersnormalbrainwavepatterns
AT aldebaranmhofer temporalablationoftheciliaryproteinift88altersnormalbrainwavepatterns
AT xuanmaochen temporalablationoftheciliaryproteinift88altersnormalbrainwavepatterns