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Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social Memory and Synaptic Functions in the Hippocampus

Disrupted-in-schizophrenia 1 (DISC1) is a strong candidate susceptibility gene for a spectrum of neuropsychiatric diseases including schizophrenia, bipolar disorder and major depression, all of which are thought to result from interactions between gene mutations and environmental risk factors such a...

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Autores principales: Li, Nan, Cui, Lin, Song, Ge, Guo, Li, Gu, Huating, Cao, Haisheng, Li, Guo-Dong, Zhou, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082952/
https://www.ncbi.nlm.nih.gov/pubmed/30116177
http://dx.doi.org/10.3389/fncel.2018.00238
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author Li, Nan
Cui, Lin
Song, Ge
Guo, Li
Gu, Huating
Cao, Haisheng
Li, Guo-Dong
Zhou, Yu
author_facet Li, Nan
Cui, Lin
Song, Ge
Guo, Li
Gu, Huating
Cao, Haisheng
Li, Guo-Dong
Zhou, Yu
author_sort Li, Nan
collection PubMed
description Disrupted-in-schizophrenia 1 (DISC1) is a strong candidate susceptibility gene for a spectrum of neuropsychiatric diseases including schizophrenia, bipolar disorder and major depression, all of which are thought to result from interactions between gene mutations and environmental risk factors such as influenza, trauma and stress. Adolescence is a key period susceptible to stress and stress-related mental illnesses. In a previous study, we found that although DISC1 L100P point mutation mice shows object recognition deficits, their sociability and social memory are relatively normal. Therefore, in this article, we investigated whether the interaction between adolescent stress and DISC1 L100P point mutation affects adult social memory, and we explored the underlying mechanisms. We found that adolescent stress (isolation from 5 weeks to 8 weeks of age) specifically impaired social memory of adult DISC1 L100P mice but not that of WT littermates, which could be rescued by administration of atypical antipsychotic drug clozapine. On the other hand, it did not induce anxiety or depression in adult mice. Adolescent isolation exacerbated adult neurogenesis deficits in the hippocampus of DISC1 L100P mice, while it had no effect on WT mice. In addition, we found that adolescent isolation led to long lasting changes in synaptic transmission and plasticity in the hippocampal circuits, some of which are specific for DISC1 L100P mice. In summary, we identified here the specific interaction between genetic mutation (DISC1 L100P) and adolescence social stress that damages synaptic function and social memory in adult hippocampal circuits. Highlights: –. Adolescent isolation (from 5 weeks to 8 weeks of age) impairs adult social memory when combined with DISC1 L100P point mutation. –. Adolescent isolation exacerbates adult neurogenesis deficit in the hippocampus of L100P mice but has no similar effect on WT mice. –. Adolescent isolation causes long lasting changes in synaptic transmission and plasticity of the hippocampal network in DISC1 L100P mice.
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spelling pubmed-60829522018-08-16 Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social Memory and Synaptic Functions in the Hippocampus Li, Nan Cui, Lin Song, Ge Guo, Li Gu, Huating Cao, Haisheng Li, Guo-Dong Zhou, Yu Front Cell Neurosci Neuroscience Disrupted-in-schizophrenia 1 (DISC1) is a strong candidate susceptibility gene for a spectrum of neuropsychiatric diseases including schizophrenia, bipolar disorder and major depression, all of which are thought to result from interactions between gene mutations and environmental risk factors such as influenza, trauma and stress. Adolescence is a key period susceptible to stress and stress-related mental illnesses. In a previous study, we found that although DISC1 L100P point mutation mice shows object recognition deficits, their sociability and social memory are relatively normal. Therefore, in this article, we investigated whether the interaction between adolescent stress and DISC1 L100P point mutation affects adult social memory, and we explored the underlying mechanisms. We found that adolescent stress (isolation from 5 weeks to 8 weeks of age) specifically impaired social memory of adult DISC1 L100P mice but not that of WT littermates, which could be rescued by administration of atypical antipsychotic drug clozapine. On the other hand, it did not induce anxiety or depression in adult mice. Adolescent isolation exacerbated adult neurogenesis deficits in the hippocampus of DISC1 L100P mice, while it had no effect on WT mice. In addition, we found that adolescent isolation led to long lasting changes in synaptic transmission and plasticity in the hippocampal circuits, some of which are specific for DISC1 L100P mice. In summary, we identified here the specific interaction between genetic mutation (DISC1 L100P) and adolescence social stress that damages synaptic function and social memory in adult hippocampal circuits. Highlights: –. Adolescent isolation (from 5 weeks to 8 weeks of age) impairs adult social memory when combined with DISC1 L100P point mutation. –. Adolescent isolation exacerbates adult neurogenesis deficit in the hippocampus of L100P mice but has no similar effect on WT mice. –. Adolescent isolation causes long lasting changes in synaptic transmission and plasticity of the hippocampal network in DISC1 L100P mice. Frontiers Media S.A. 2018-08-02 /pmc/articles/PMC6082952/ /pubmed/30116177 http://dx.doi.org/10.3389/fncel.2018.00238 Text en Copyright © 2018 Li, Cui, Song, Guo, Gu, Cao, Li and Zhou. 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
Li, Nan
Cui, Lin
Song, Ge
Guo, Li
Gu, Huating
Cao, Haisheng
Li, Guo-Dong
Zhou, Yu
Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social Memory and Synaptic Functions in the Hippocampus
title Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social Memory and Synaptic Functions in the Hippocampus
title_full Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social Memory and Synaptic Functions in the Hippocampus
title_fullStr Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social Memory and Synaptic Functions in the Hippocampus
title_full_unstemmed Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social Memory and Synaptic Functions in the Hippocampus
title_short Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social Memory and Synaptic Functions in the Hippocampus
title_sort adolescent isolation interacts with disc1 point mutation to impair adult social memory and synaptic functions in the hippocampus
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082952/
https://www.ncbi.nlm.nih.gov/pubmed/30116177
http://dx.doi.org/10.3389/fncel.2018.00238
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