A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment

English version

Autoři: Thomas K. Pak ^aff001; Calvin S. Carter ^aff003; Qihong Zhang ^aff003; Sunny C. Huang ^aff001; Charles Searby ^aff003; Ying Hsu ^aff003; Rebecca J. Taugher ^aff004; Tim Vogel ^aff003; Christopher C. Cychosz ^aff006; Rachel Genova ^aff001; Nina N. Moreira ^aff007; Hanna Stevens ^aff002; John A. Wemmie ^aff002; Andrew A. Pieper ^aff009; Kai Wang ^aff015; Val C. Sheffield ^aff002
Působiště autorů: Medical Scientist Training Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America ^aff001; Neuroscience Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America ^aff002; Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America ^aff003; Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America ^aff004; Department of Veterans Affairs Medical Center, Iowa City, Iowa, United States of America ^aff005; Department of Orthopedics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America ^aff006; Department of Obstetrics and Gynecology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America ^aff007; Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America ^aff008; Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States of America ^aff009; Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio, United States of America ^aff010; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, Ohio, United States of America ^aff011; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America ^aff012; Weill Cornell Autism Research Program, Weill Cornell Medicine of Cornell University, New York, United States of America ^aff013; Department of Neuroscience, Case Western Reserve University, School of Medicine, Cleveland, Ohio, United States of America ^aff014; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, United States of America ^aff015
Vyšlo v časopise: A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment. PLoS Genet 17(4): e1009484. doi:10.1371/journal.pgen.1009484
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009484

Souhrn

Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS). Here, we demonstrate that BBS mice have significant impairments in context fear conditioning, a form of associative learning. Moreover, we show that postnatal deletion of BBS gene function, as well as congenital deletion, specifically in the forebrain, impairs context fear conditioning. Analyses indicated that these behavioral impairments are not the result of impaired hippocampal long-term potentiation. However, our results indicate that these behavioral impairments are the result of impaired hippocampal neurogenesis. Two-week treatment with lithium chloride partially restores the proliferation of hippocampal neurons which leads to a rescue of context fear conditioning. Overall, our results identify a novel role of cilia genes in hippocampal neurogenesis and long-term context fear conditioning.

Klíčová slova:

Cilia – Fear conditioning – Genetically modified animals – Hippocampal neurogenesis – Hippocampus – Lithium – Mice – Mouse models

Zdroje

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