DHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid Haemorrhage
Abstract Background Microglia are resident immune cells in the central nervous system and central to the innate immune system. Excessive activation of microglia after subarachnoid haemorrhage (SAH) contributes greatly to early brain injury, which is responsible for poor outcomes. Dehydroepiandroster...
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doaj-fd81e2c98f4b4b0cbda3b13148200f662020-11-29T12:08:34ZengBMCJournal of Neuroinflammation1742-20942019-11-0116111410.1186/s12974-019-1641-yDHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid HaemorrhageTao Tao0Guang-Jie Liu1Xuan Shi2Yan Zhou3Yue Lu4Yong-Yue Gao5Xiang-Sheng Zhang6Han Wang7Ling-Yun Wu8Chun-Lei Chen9Zong Zhuang10Wei Li11Chun-Hua Hang12Department of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Neurology, Jinling Hospital, Nanjing Medical UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Neurosurgery, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityAbstract Background Microglia are resident immune cells in the central nervous system and central to the innate immune system. Excessive activation of microglia after subarachnoid haemorrhage (SAH) contributes greatly to early brain injury, which is responsible for poor outcomes. Dehydroepiandrosterone (DHEA), a steroid hormone enriched in the brain, has recently been found to regulate microglial activation. The purpose of this study was to address the role of DHEA in SAH. Methods We used in vivo models of endovascular perforation and in vitro models of haemoglobin exposure to illustrate the effects of DHEA on microglia in SAH. Results In experimental SAH mice, exogenous DHEA administration increased DHEA levels in the brain and modulated microglial activation. Ameliorated neuronal damage and improved neurological outcomes were also observed in the SAH mice pretreated with DHEA, suggesting neuronal protective effects of DHEA. In cultured microglia, DHEA elevated the mRNA and protein levels of Jumonji d3 (JMJD3, histone 3 demethylase) after haemoglobin exposure, downregulated the H3K27me3 level, and inhibited the transcription of proinflammatory genes. The devastating proinflammatory microglia-mediated effects on primary neurons were also attenuated by DHEA; however, specific inhibition of JMJD3 abolished the protective effects of DHEA. We next verified that DHEA-induced JMJD3 expression, at least in part, through the tropomyosin-related kinase A (TrkA)/Akt signalling pathway. Conclusions DHEA has a neuroprotective effect after SAH. Moreover, DHEA increases microglial JMJD3 expression to regulate proinflammatory/anti-inflammatory microglial activation after haemoglobin exposure, thereby suppressing inflammation.https://doi.org/10.1186/s12974-019-1641-yDehydroepiandrosteroneMicrogliaJMJD3Subarachnoid haemorrhageInflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tao Tao Guang-Jie Liu Xuan Shi Yan Zhou Yue Lu Yong-Yue Gao Xiang-Sheng Zhang Han Wang Ling-Yun Wu Chun-Lei Chen Zong Zhuang Wei Li Chun-Hua Hang |
spellingShingle |
Tao Tao Guang-Jie Liu Xuan Shi Yan Zhou Yue Lu Yong-Yue Gao Xiang-Sheng Zhang Han Wang Ling-Yun Wu Chun-Lei Chen Zong Zhuang Wei Li Chun-Hua Hang DHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid Haemorrhage Journal of Neuroinflammation Dehydroepiandrosterone Microglia JMJD3 Subarachnoid haemorrhage Inflammation |
author_facet |
Tao Tao Guang-Jie Liu Xuan Shi Yan Zhou Yue Lu Yong-Yue Gao Xiang-Sheng Zhang Han Wang Ling-Yun Wu Chun-Lei Chen Zong Zhuang Wei Li Chun-Hua Hang |
author_sort |
Tao Tao |
title |
DHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid Haemorrhage |
title_short |
DHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid Haemorrhage |
title_full |
DHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid Haemorrhage |
title_fullStr |
DHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid Haemorrhage |
title_full_unstemmed |
DHEA Attenuates Microglial Activation via Induction of JMJD3 in Experimental Subarachnoid Haemorrhage |
title_sort |
dhea attenuates microglial activation via induction of jmjd3 in experimental subarachnoid haemorrhage |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2019-11-01 |
description |
Abstract Background Microglia are resident immune cells in the central nervous system and central to the innate immune system. Excessive activation of microglia after subarachnoid haemorrhage (SAH) contributes greatly to early brain injury, which is responsible for poor outcomes. Dehydroepiandrosterone (DHEA), a steroid hormone enriched in the brain, has recently been found to regulate microglial activation. The purpose of this study was to address the role of DHEA in SAH. Methods We used in vivo models of endovascular perforation and in vitro models of haemoglobin exposure to illustrate the effects of DHEA on microglia in SAH. Results In experimental SAH mice, exogenous DHEA administration increased DHEA levels in the brain and modulated microglial activation. Ameliorated neuronal damage and improved neurological outcomes were also observed in the SAH mice pretreated with DHEA, suggesting neuronal protective effects of DHEA. In cultured microglia, DHEA elevated the mRNA and protein levels of Jumonji d3 (JMJD3, histone 3 demethylase) after haemoglobin exposure, downregulated the H3K27me3 level, and inhibited the transcription of proinflammatory genes. The devastating proinflammatory microglia-mediated effects on primary neurons were also attenuated by DHEA; however, specific inhibition of JMJD3 abolished the protective effects of DHEA. We next verified that DHEA-induced JMJD3 expression, at least in part, through the tropomyosin-related kinase A (TrkA)/Akt signalling pathway. Conclusions DHEA has a neuroprotective effect after SAH. Moreover, DHEA increases microglial JMJD3 expression to regulate proinflammatory/anti-inflammatory microglial activation after haemoglobin exposure, thereby suppressing inflammation. |
topic |
Dehydroepiandrosterone Microglia JMJD3 Subarachnoid haemorrhage Inflammation |
url |
https://doi.org/10.1186/s12974-019-1641-y |
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