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Mice Genetically Depleted of Brain Serotonin Display Social Impairments, Communication Deficits and Repetitive Behaviors: Possible Relevance to Autism

Autism is a complex neurodevelopmental disorder characterized by impaired reciprocal social interaction, communication deficits and repetitive behaviors. A very large number of genes have been linked to autism, many of which encode proteins involved in the development and function of synaptic circui...

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Autores principales: Kane, Michael J., Angoa-Peréz, Mariana, Briggs, Denise I., Sykes, Catherine E., Francescutti, Dina M., Rosenberg, David R., Kuhn, Donald M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490915/
https://www.ncbi.nlm.nih.gov/pubmed/23139830
http://dx.doi.org/10.1371/journal.pone.0048975
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author Kane, Michael J.
Angoa-Peréz, Mariana
Briggs, Denise I.
Sykes, Catherine E.
Francescutti, Dina M.
Rosenberg, David R.
Kuhn, Donald M.
author_facet Kane, Michael J.
Angoa-Peréz, Mariana
Briggs, Denise I.
Sykes, Catherine E.
Francescutti, Dina M.
Rosenberg, David R.
Kuhn, Donald M.
author_sort Kane, Michael J.
collection PubMed
description Autism is a complex neurodevelopmental disorder characterized by impaired reciprocal social interaction, communication deficits and repetitive behaviors. A very large number of genes have been linked to autism, many of which encode proteins involved in the development and function of synaptic circuitry. However, the manner in which these mutated genes might participate, either individually or together, to cause autism is not understood. One factor known to exert extremely broad influence on brain development and network formation, and which has been linked to autism, is the neurotransmitter serotonin. Unfortunately, very little is known about how alterations in serotonin neuronal function might contribute to autism. To test the hypothesis that serotonin dysfunction can contribute to the core symptoms of autism, we analyzed mice lacking brain serotonin (via a null mutation in the gene for tryptophan hydroxylase 2 (TPH2)) for behaviors that are relevant to this disorder. Mice lacking brain serotonin (TPH2−/−) showed substantial deficits in numerous validated tests of social interaction and communication. These mice also display highly repetitive and compulsive behaviors. Newborn TPH2−/− mutant mice show delays in the expression of key developmental milestones and their diminished preference for maternal scents over the scent of an unrelated female is a forerunner of more severe socialization deficits that emerge in weanlings and persist into adulthood. Taken together, these results indicate that a hypo-serotonin condition can lead to behavioral traits that are highly characteristic of autism. Our findings should stimulate new studies that focus on determining how brain hyposerotonemia during critical neurodevelopmental periods can alter the maturation of synaptic circuits known to be mis-wired in autism and how prevention of such deficits might prevent this disorder.
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spelling pubmed-34909152012-11-08 Mice Genetically Depleted of Brain Serotonin Display Social Impairments, Communication Deficits and Repetitive Behaviors: Possible Relevance to Autism Kane, Michael J. Angoa-Peréz, Mariana Briggs, Denise I. Sykes, Catherine E. Francescutti, Dina M. Rosenberg, David R. Kuhn, Donald M. PLoS One Research Article Autism is a complex neurodevelopmental disorder characterized by impaired reciprocal social interaction, communication deficits and repetitive behaviors. A very large number of genes have been linked to autism, many of which encode proteins involved in the development and function of synaptic circuitry. However, the manner in which these mutated genes might participate, either individually or together, to cause autism is not understood. One factor known to exert extremely broad influence on brain development and network formation, and which has been linked to autism, is the neurotransmitter serotonin. Unfortunately, very little is known about how alterations in serotonin neuronal function might contribute to autism. To test the hypothesis that serotonin dysfunction can contribute to the core symptoms of autism, we analyzed mice lacking brain serotonin (via a null mutation in the gene for tryptophan hydroxylase 2 (TPH2)) for behaviors that are relevant to this disorder. Mice lacking brain serotonin (TPH2−/−) showed substantial deficits in numerous validated tests of social interaction and communication. These mice also display highly repetitive and compulsive behaviors. Newborn TPH2−/− mutant mice show delays in the expression of key developmental milestones and their diminished preference for maternal scents over the scent of an unrelated female is a forerunner of more severe socialization deficits that emerge in weanlings and persist into adulthood. Taken together, these results indicate that a hypo-serotonin condition can lead to behavioral traits that are highly characteristic of autism. Our findings should stimulate new studies that focus on determining how brain hyposerotonemia during critical neurodevelopmental periods can alter the maturation of synaptic circuits known to be mis-wired in autism and how prevention of such deficits might prevent this disorder. Public Library of Science 2012-11-06 /pmc/articles/PMC3490915/ /pubmed/23139830 http://dx.doi.org/10.1371/journal.pone.0048975 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Kane, Michael J.
Angoa-Peréz, Mariana
Briggs, Denise I.
Sykes, Catherine E.
Francescutti, Dina M.
Rosenberg, David R.
Kuhn, Donald M.
Mice Genetically Depleted of Brain Serotonin Display Social Impairments, Communication Deficits and Repetitive Behaviors: Possible Relevance to Autism
title Mice Genetically Depleted of Brain Serotonin Display Social Impairments, Communication Deficits and Repetitive Behaviors: Possible Relevance to Autism
title_full Mice Genetically Depleted of Brain Serotonin Display Social Impairments, Communication Deficits and Repetitive Behaviors: Possible Relevance to Autism
title_fullStr Mice Genetically Depleted of Brain Serotonin Display Social Impairments, Communication Deficits and Repetitive Behaviors: Possible Relevance to Autism
title_full_unstemmed Mice Genetically Depleted of Brain Serotonin Display Social Impairments, Communication Deficits and Repetitive Behaviors: Possible Relevance to Autism
title_short Mice Genetically Depleted of Brain Serotonin Display Social Impairments, Communication Deficits and Repetitive Behaviors: Possible Relevance to Autism
title_sort mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors: possible relevance to autism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490915/
https://www.ncbi.nlm.nih.gov/pubmed/23139830
http://dx.doi.org/10.1371/journal.pone.0048975
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