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Increased Axin expression enhances adult hippocampal neurogenesis and exerts an antidepressant effect

Major depressive disorders are emerging health problems that affect millions of people worldwide. However, treatment options and targets for drug development are limited. Impaired adult hippocampal neurogenesis is emerging as a key contributor to the pathology of major depressive disorders. We previ...

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Autores principales: Chen, Wei-Wei, Fu, Wing-Yu, Su, Yi-Ting, Fang, Wei-Qun, Fu, Amy K. Y., Ip, Nancy Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362220/
https://www.ncbi.nlm.nih.gov/pubmed/30718786
http://dx.doi.org/10.1038/s41598-018-38103-3
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author Chen, Wei-Wei
Fu, Wing-Yu
Su, Yi-Ting
Fang, Wei-Qun
Fu, Amy K. Y.
Ip, Nancy Y.
author_facet Chen, Wei-Wei
Fu, Wing-Yu
Su, Yi-Ting
Fang, Wei-Qun
Fu, Amy K. Y.
Ip, Nancy Y.
author_sort Chen, Wei-Wei
collection PubMed
description Major depressive disorders are emerging health problems that affect millions of people worldwide. However, treatment options and targets for drug development are limited. Impaired adult hippocampal neurogenesis is emerging as a key contributor to the pathology of major depressive disorders. We previously demonstrated that increasing the expression of the multifunctional scaffold protein Axis inhibition protein (Axin) by administration of the small molecule XAV939 enhances embryonic neurogenesis and affects social interaction behaviors. This prompted us to examine whether increasing Axin protein level can enhance adult hippocampal neurogenesis and thus contribute to mood regulation. Here, we report that stabilizing Axin increases adult hippocampal neurogenesis and exerts an antidepressant effect. Specifically, treating adult mice with XAV939 increased the amplification of adult neural progenitor cells and neuron production in the hippocampus under both normal and chronic stress conditions. Furthermore, XAV939 injection in mice ameliorated depression-like behaviors induced by chronic restraint stress. Thus, our study demonstrates that Axin/XAV939 plays an important role in adult hippocampal neurogenesis and provides a potential therapeutic approach for mood-related disorders.
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spelling pubmed-63622202019-02-06 Increased Axin expression enhances adult hippocampal neurogenesis and exerts an antidepressant effect Chen, Wei-Wei Fu, Wing-Yu Su, Yi-Ting Fang, Wei-Qun Fu, Amy K. Y. Ip, Nancy Y. Sci Rep Article Major depressive disorders are emerging health problems that affect millions of people worldwide. However, treatment options and targets for drug development are limited. Impaired adult hippocampal neurogenesis is emerging as a key contributor to the pathology of major depressive disorders. We previously demonstrated that increasing the expression of the multifunctional scaffold protein Axis inhibition protein (Axin) by administration of the small molecule XAV939 enhances embryonic neurogenesis and affects social interaction behaviors. This prompted us to examine whether increasing Axin protein level can enhance adult hippocampal neurogenesis and thus contribute to mood regulation. Here, we report that stabilizing Axin increases adult hippocampal neurogenesis and exerts an antidepressant effect. Specifically, treating adult mice with XAV939 increased the amplification of adult neural progenitor cells and neuron production in the hippocampus under both normal and chronic stress conditions. Furthermore, XAV939 injection in mice ameliorated depression-like behaviors induced by chronic restraint stress. Thus, our study demonstrates that Axin/XAV939 plays an important role in adult hippocampal neurogenesis and provides a potential therapeutic approach for mood-related disorders. Nature Publishing Group UK 2019-02-04 /pmc/articles/PMC6362220/ /pubmed/30718786 http://dx.doi.org/10.1038/s41598-018-38103-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Wei-Wei
Fu, Wing-Yu
Su, Yi-Ting
Fang, Wei-Qun
Fu, Amy K. Y.
Ip, Nancy Y.
Increased Axin expression enhances adult hippocampal neurogenesis and exerts an antidepressant effect
title Increased Axin expression enhances adult hippocampal neurogenesis and exerts an antidepressant effect
title_full Increased Axin expression enhances adult hippocampal neurogenesis and exerts an antidepressant effect
title_fullStr Increased Axin expression enhances adult hippocampal neurogenesis and exerts an antidepressant effect
title_full_unstemmed Increased Axin expression enhances adult hippocampal neurogenesis and exerts an antidepressant effect
title_short Increased Axin expression enhances adult hippocampal neurogenesis and exerts an antidepressant effect
title_sort increased axin expression enhances adult hippocampal neurogenesis and exerts an antidepressant effect
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362220/
https://www.ncbi.nlm.nih.gov/pubmed/30718786
http://dx.doi.org/10.1038/s41598-018-38103-3
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