Stably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral hemorrhage

Stably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral hemorrhage

Abstract Mesolimbic dopamine (DA) system lesion plays a key role in the pathophysiology of depression, and our previous study demonstrated that reduced microtubule (MT) stability aggravated nigrostriatal pathway impairment after intracerebral hemorrhage (ICH). This study aimed to further investigate...

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Autores principales: Yang Yang, Kaiyuan Zhang, Jun Zhong, Ju Wang, Zhongyuan Yu, Xuejiao Lei, Xuezhu Chen, Yulian Quan, Jishu Xian, Yujie Chen, Xin Liu, Hua Feng, Liang Tan
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/7737c679375d40828a949cecde396ab5
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spelling oai:doaj.org-article:7737c679375d40828a949cecde396ab52021-12-02T15:08:35ZStably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral hemorrhage10.1038/s41598-018-31056-72045-2322https://doaj.org/article/7737c679375d40828a949cecde396ab52018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31056-7https://doaj.org/toc/2045-2322Abstract Mesolimbic dopamine (DA) system lesion plays a key role in the pathophysiology of depression, and our previous study demonstrated that reduced microtubule (MT) stability aggravated nigrostriatal pathway impairment after intracerebral hemorrhage (ICH). This study aimed to further investigate the occurrence regularity of depression-like behavior after ICH and determine whether maintaining MT stabilization could protect DA neurons in ventral tegmental area (VTA) and alleviate depression-like behavior after ICH. An intrastriatal injection of 20 μl of autologous blood or MT depolymerization reagent nocodazole (Noco) was used to mimic the pathology of ICH model in mice. The concentration of DA, number of DA neurons and acetylated α-tubulin (a marker for stable MT) in VTA were checked, and depression-related behavior tests were performed after ICH. A MT-stabilizing agent, epothilone B (EpoB), was administered to explore the effects of MT stabilization on DA neurons and depression-like behavior after ICH. The results showed that obvious depression-like behavior occurred at 7, 14, and 28 days (P < 0.01) after ICH. These time-points were related to significant decreases in the concentration of DA (P < 0.01) and number of DA neurons (P < 0.01) in VTA. Moreover, The decrease of acetylated α-tubulin expression after ICH and Noco injection contributed to DA neurons’ impairment in VTA, and Noco injecton also aggravate ICH-induced depression-like behaviors and DA neurons’ injury. Furthermore, EpoB treatment significantly ameliorated ICH and Noco-induced depression-like behaviors (P < 0.05) and increased the concentration of DA (P < 0.05) and number of DA neurons (P < 0.05) in VTA by increasing the level of acetylated α-tubulin. The results indicate that EpoB can protect DA neurons by enhancing MT stability, and alleviate post-ICH depressive behaviors. This MT-targeted therapeutic strategy shows promise as a bench-to-bedside translational method for treating depression after ICH.Yang YangKaiyuan ZhangJun ZhongJu WangZhongyuan YuXuejiao LeiXuezhu ChenYulian QuanJishu XianYujie ChenXin LiuHua FengLiang TanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yang Yang
Kaiyuan Zhang
Jun Zhong
Ju Wang
Zhongyuan Yu
Xuejiao Lei
Xuezhu Chen
Yulian Quan
Jishu Xian
Yujie Chen
Xin Liu
Hua Feng
Liang Tan
Stably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral hemorrhage
description Abstract Mesolimbic dopamine (DA) system lesion plays a key role in the pathophysiology of depression, and our previous study demonstrated that reduced microtubule (MT) stability aggravated nigrostriatal pathway impairment after intracerebral hemorrhage (ICH). This study aimed to further investigate the occurrence regularity of depression-like behavior after ICH and determine whether maintaining MT stabilization could protect DA neurons in ventral tegmental area (VTA) and alleviate depression-like behavior after ICH. An intrastriatal injection of 20 μl of autologous blood or MT depolymerization reagent nocodazole (Noco) was used to mimic the pathology of ICH model in mice. The concentration of DA, number of DA neurons and acetylated α-tubulin (a marker for stable MT) in VTA were checked, and depression-related behavior tests were performed after ICH. A MT-stabilizing agent, epothilone B (EpoB), was administered to explore the effects of MT stabilization on DA neurons and depression-like behavior after ICH. The results showed that obvious depression-like behavior occurred at 7, 14, and 28 days (P < 0.01) after ICH. These time-points were related to significant decreases in the concentration of DA (P < 0.01) and number of DA neurons (P < 0.01) in VTA. Moreover, The decrease of acetylated α-tubulin expression after ICH and Noco injection contributed to DA neurons’ impairment in VTA, and Noco injecton also aggravate ICH-induced depression-like behaviors and DA neurons’ injury. Furthermore, EpoB treatment significantly ameliorated ICH and Noco-induced depression-like behaviors (P < 0.05) and increased the concentration of DA (P < 0.05) and number of DA neurons (P < 0.05) in VTA by increasing the level of acetylated α-tubulin. The results indicate that EpoB can protect DA neurons by enhancing MT stability, and alleviate post-ICH depressive behaviors. This MT-targeted therapeutic strategy shows promise as a bench-to-bedside translational method for treating depression after ICH.
format article
author Yang Yang
Kaiyuan Zhang
Jun Zhong
Ju Wang
Zhongyuan Yu
Xuejiao Lei
Xuezhu Chen
Yulian Quan
Jishu Xian
Yujie Chen
Xin Liu
Hua Feng
Liang Tan
author_facet Yang Yang
Kaiyuan Zhang
Jun Zhong
Ju Wang
Zhongyuan Yu
Xuejiao Lei
Xuezhu Chen
Yulian Quan
Jishu Xian
Yujie Chen
Xin Liu
Hua Feng
Liang Tan
author_sort Yang Yang
title Stably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral hemorrhage
title_short Stably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral hemorrhage
title_full Stably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral hemorrhage
title_fullStr Stably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral hemorrhage
title_full_unstemmed Stably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral hemorrhage
title_sort stably maintained microtubules protect dopamine neurons and alleviate depression-like behavior after intracerebral hemorrhage
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/7737c679375d40828a949cecde396ab5
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