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Sex-Dependent Motor Deficit and Increased Anxiety-Like States in Mice Lacking Autism-Associated Gene Slit3

Altered neuronal connectivity has been implicated in the pathophysiology of Autism Spectrum Disorder (ASD). SLIT/ROBO signaling plays an important role in developmental processes of neuronal connectivity, including axon guidance, neuronal migration, and axonal and dendritic branching. Genetic eviden...

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Autores principales: Park, Su Mi, Plachez, Céline, Huang, Shiyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243047/
https://www.ncbi.nlm.nih.gov/pubmed/30483073
http://dx.doi.org/10.3389/fnbeh.2018.00261
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author Park, Su Mi
Plachez, Céline
Huang, Shiyong
author_facet Park, Su Mi
Plachez, Céline
Huang, Shiyong
author_sort Park, Su Mi
collection PubMed
description Altered neuronal connectivity has been implicated in the pathophysiology of Autism Spectrum Disorder (ASD). SLIT/ROBO signaling plays an important role in developmental processes of neuronal connectivity, including axon guidance, neuronal migration, and axonal and dendritic branching. Genetic evidence supports that SLIT3, one of the genes encoding SLITs, is associated with ASD. Yet the causal link between SLIT3 mutation and autism symptoms has not been examined. Here we assessed ASD-associated behaviors in Slit3 knockout (KO) mice. Our data showed that Slit3-KO mice exhibited reduced marble burying behaviors but normal social behaviors. In addition, Slit3-KO mice displayed hypolocomotion in the open field test and impaired motor coordination in the rotarod test. Anxiety-like behaviors were mainly observed in female KO mice assessed by three types of behavioral tests, namely, the open field test, elevated plus maze test, and light/dark box test. No differences were observed between KO and wildtype mice in recognition memory in the novel object recognition test or depression-like behavior in the tail suspension test. Taken together, loss of Slit3 may result in disrupted neural circuits related to motor function and increased anxiety-like states, which are co-occurring symptoms in ASD.
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spelling pubmed-62430472018-11-27 Sex-Dependent Motor Deficit and Increased Anxiety-Like States in Mice Lacking Autism-Associated Gene Slit3 Park, Su Mi Plachez, Céline Huang, Shiyong Front Behav Neurosci Neuroscience Altered neuronal connectivity has been implicated in the pathophysiology of Autism Spectrum Disorder (ASD). SLIT/ROBO signaling plays an important role in developmental processes of neuronal connectivity, including axon guidance, neuronal migration, and axonal and dendritic branching. Genetic evidence supports that SLIT3, one of the genes encoding SLITs, is associated with ASD. Yet the causal link between SLIT3 mutation and autism symptoms has not been examined. Here we assessed ASD-associated behaviors in Slit3 knockout (KO) mice. Our data showed that Slit3-KO mice exhibited reduced marble burying behaviors but normal social behaviors. In addition, Slit3-KO mice displayed hypolocomotion in the open field test and impaired motor coordination in the rotarod test. Anxiety-like behaviors were mainly observed in female KO mice assessed by three types of behavioral tests, namely, the open field test, elevated plus maze test, and light/dark box test. No differences were observed between KO and wildtype mice in recognition memory in the novel object recognition test or depression-like behavior in the tail suspension test. Taken together, loss of Slit3 may result in disrupted neural circuits related to motor function and increased anxiety-like states, which are co-occurring symptoms in ASD. Frontiers Media S.A. 2018-11-13 /pmc/articles/PMC6243047/ /pubmed/30483073 http://dx.doi.org/10.3389/fnbeh.2018.00261 Text en Copyright © 2018 Park, Plachez and Huang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Park, Su Mi
Plachez, Céline
Huang, Shiyong
Sex-Dependent Motor Deficit and Increased Anxiety-Like States in Mice Lacking Autism-Associated Gene Slit3
title Sex-Dependent Motor Deficit and Increased Anxiety-Like States in Mice Lacking Autism-Associated Gene Slit3
title_full Sex-Dependent Motor Deficit and Increased Anxiety-Like States in Mice Lacking Autism-Associated Gene Slit3
title_fullStr Sex-Dependent Motor Deficit and Increased Anxiety-Like States in Mice Lacking Autism-Associated Gene Slit3
title_full_unstemmed Sex-Dependent Motor Deficit and Increased Anxiety-Like States in Mice Lacking Autism-Associated Gene Slit3
title_short Sex-Dependent Motor Deficit and Increased Anxiety-Like States in Mice Lacking Autism-Associated Gene Slit3
title_sort sex-dependent motor deficit and increased anxiety-like states in mice lacking autism-associated gene slit3
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243047/
https://www.ncbi.nlm.nih.gov/pubmed/30483073
http://dx.doi.org/10.3389/fnbeh.2018.00261
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