title: Abnormal intrinsic dynamics of dendritic spines in a fragile X syndrome mouse model in vivo.
abstract: Dendritic spine generation and elimination play an important role in learning and memory, the dynamics of which have been examined within the neocortex in vivo. Spine turnover has also been detected in the absence of specific learning tasks, and is frequently exaggerated in animal models of autistic spectrum disorder (ASD). The present study aimed to examine whether the baseline rate of spine turnover was activity-dependent. This was achieved using a microfluidic brain interface and open-dura surgery, with the goal of abolishing neuronal Ca(2+) signaling in the visual cortex of wild-type mice and rodent models of fragile X syndrome (Fmr1 knockout [KO]). In wild-type and Fmr1 KO mice, the majority of baseline turnover was found to be activity-independent. Accordingly, the application of matrix metalloproteinase-9 inhibitors selectively restored the abnormal spine dynamics observed in Fmr1 KO mice, without affecting the intrinsic dynamics of spine turnover in wild-type mice. Such findings indicate that the baseline turnover of dendritic spines is mediated by activity-independent intrinsic dynamics. Furthermore, these results suggest that the targeting of abnormal intrinsic dynamics might pose a novel therapy for ASD.
authors.affiliation: Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.|CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nagaoka
authors.affiliation: Department of Bioengineering, School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takehara
authors.affiliation: Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.|Laboratory of Medical Neuroscience, Institute for Molecular and Cellular Regulation, Gunma University, Maebachi-city, Gunma 371-8512, Japan.|PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hayashi-Takagi
authors.affiliation: Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.|CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Noguchi
authors.affiliation: Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.|CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.|Department of Neurosurgery, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.|CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Fukutoshi
authors.initials: F
authors.lastname: Shirai
authors.affiliation: Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.|CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yagishita
authors.affiliation: Department of Bioengineering, School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Akagi
authors.affiliation: Department of Bioengineering, School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ichiki
authors.affiliation: Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.|CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Kasai
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D014793:Visual Cortex / Q000378:metabolism* / Q000473:pathology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse