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Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice

Dysregulation of the immune system contributes to the pathogenesis of neuropsychiatric disorders including schizophrenia. Here, we demonstrated that toll-like receptor (TLR)-2, a family of pattern-recognition receptors, is involved in the pathogenesis of schizophrenia-like symptoms. Psychotic sympto...

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Autores principales: Park, Se Jin, Lee, Jee Youn, Kim, Sang Jeong, Choi, Se-Young, Yune, Tae Young, Ryu, Jong Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330527/
https://www.ncbi.nlm.nih.gov/pubmed/25687169
http://dx.doi.org/10.1038/srep08502
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author Park, Se Jin
Lee, Jee Youn
Kim, Sang Jeong
Choi, Se-Young
Yune, Tae Young
Ryu, Jong Hoon
author_facet Park, Se Jin
Lee, Jee Youn
Kim, Sang Jeong
Choi, Se-Young
Yune, Tae Young
Ryu, Jong Hoon
author_sort Park, Se Jin
collection PubMed
description Dysregulation of the immune system contributes to the pathogenesis of neuropsychiatric disorders including schizophrenia. Here, we demonstrated that toll-like receptor (TLR)-2, a family of pattern-recognition receptors, is involved in the pathogenesis of schizophrenia-like symptoms. Psychotic symptoms such as hyperlocomotion, anxiolytic-like behaviors, prepulse inhibition deficits, social withdrawal, and cognitive impairments were observed in TLR-2 knock-out (KO) mice. Ventricle enlargement, a hallmark of schizophrenia, was also observed in TLR-2 KO mouse brains. Levels of p-Akt and p-GSK-3α/β were markedly higher in the brain of TLR-2 KO than wild-type (WT) mice. Antipsychotic drugs such as haloperidol or clozapine reversed behavioral and biochemical alterations in TLR-2 KO mice. Furthermore, p-Akt and p-GSK-3α/β were decreased by treatment with a TLR-2 ligand, lipoteichoic acid, in WT mice. Thus, our data suggest that the dysregulation of the innate immune system by a TLR-2 deficiency may contribute to the development and/or pathophysiology of schizophrenia-like behaviors via Akt-GSK-3α/β signaling.
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spelling pubmed-43305272015-02-23 Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice Park, Se Jin Lee, Jee Youn Kim, Sang Jeong Choi, Se-Young Yune, Tae Young Ryu, Jong Hoon Sci Rep Article Dysregulation of the immune system contributes to the pathogenesis of neuropsychiatric disorders including schizophrenia. Here, we demonstrated that toll-like receptor (TLR)-2, a family of pattern-recognition receptors, is involved in the pathogenesis of schizophrenia-like symptoms. Psychotic symptoms such as hyperlocomotion, anxiolytic-like behaviors, prepulse inhibition deficits, social withdrawal, and cognitive impairments were observed in TLR-2 knock-out (KO) mice. Ventricle enlargement, a hallmark of schizophrenia, was also observed in TLR-2 KO mouse brains. Levels of p-Akt and p-GSK-3α/β were markedly higher in the brain of TLR-2 KO than wild-type (WT) mice. Antipsychotic drugs such as haloperidol or clozapine reversed behavioral and biochemical alterations in TLR-2 KO mice. Furthermore, p-Akt and p-GSK-3α/β were decreased by treatment with a TLR-2 ligand, lipoteichoic acid, in WT mice. Thus, our data suggest that the dysregulation of the innate immune system by a TLR-2 deficiency may contribute to the development and/or pathophysiology of schizophrenia-like behaviors via Akt-GSK-3α/β signaling. Nature Publishing Group 2015-02-17 /pmc/articles/PMC4330527/ /pubmed/25687169 http://dx.doi.org/10.1038/srep08502 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Park, Se Jin
Lee, Jee Youn
Kim, Sang Jeong
Choi, Se-Young
Yune, Tae Young
Ryu, Jong Hoon
Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice
title Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice
title_full Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice
title_fullStr Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice
title_full_unstemmed Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice
title_short Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice
title_sort toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330527/
https://www.ncbi.nlm.nih.gov/pubmed/25687169
http://dx.doi.org/10.1038/srep08502
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