Perivascular AQP4 dysregulation in the hippocampal CA1 area after traumatic brain injury is alleviated by adenosine A2A receptor inactivation

Abstract Traumatic brain injury (TBI) can induce cognitive dysfunction due to the regional accumulation of hyperphosphorylated tau protein (p-tau). However, the factors that cause p-tau to concentrate in specific brain regions remain unclear. Here, we show that AQP4 polarization in the perivascular...

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Autores principales:	Zi-Ai Zhao, Ping Li, Shi-Yang Ye, Ya-Lei Ning, Hao Wang, Yan Peng, Nan Yang, Yan Zhao, Zhuo-Hang Zhang, Jiang-Fan Chen, Yuan-Guo Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b8e175757c444c9b2242f086186df40
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spelling	oai:doaj.org-article:8b8e175757c444c9b2242f086186df402021-12-02T15:06:18ZPerivascular AQP4 dysregulation in the hippocampal CA1 area after traumatic brain injury is alleviated by adenosine A2A receptor inactivation10.1038/s41598-017-02505-62045-2322https://doaj.org/article/8b8e175757c444c9b2242f086186df402017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02505-6https://doaj.org/toc/2045-2322Abstract Traumatic brain injury (TBI) can induce cognitive dysfunction due to the regional accumulation of hyperphosphorylated tau protein (p-tau). However, the factors that cause p-tau to concentrate in specific brain regions remain unclear. Here, we show that AQP4 polarization in the perivascular astrocytic end feet was impaired after TBI, which was most prominent in the ipsilateral brain tissue surrounding the directly impacted region and the contralateral hippocampal CA1 area and was accompanied by increased local p-tau, changes in dendritic spine density and morphology, and upregulation of the adenosine A2A receptor (A2AR). The critical role of the A2AR signaling in these pathological changes was confirmed by alleviation of the impairment of AQP4 polarity and accumulation of p-tau in the contralateral CA1 area in A2AR knockout mice. Given that p-tau can be released to the extracellular space and that the astroglial water transport via AQP4 is involved in tau clearance from the brain interstitium, our results suggest that regional disruption of AQP4 polarity following TBI may reduce the clearance of the toxic interstitial solutes such as p-tau and lead to changes in dendritic spine density and morphology. This may explain why TBI patients are more vulnerable to cognitive dysfunction.Zi-Ai ZhaoPing LiShi-Yang YeYa-Lei NingHao WangYan PengNan YangYan ZhaoZhuo-Hang ZhangJiang-Fan ChenYuan-Guo ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zi-Ai Zhao Ping Li Shi-Yang Ye Ya-Lei Ning Hao Wang Yan Peng Nan Yang Yan Zhao Zhuo-Hang Zhang Jiang-Fan Chen Yuan-Guo Zhou Perivascular AQP4 dysregulation in the hippocampal CA1 area after traumatic brain injury is alleviated by adenosine A2A receptor inactivation
description	Abstract Traumatic brain injury (TBI) can induce cognitive dysfunction due to the regional accumulation of hyperphosphorylated tau protein (p-tau). However, the factors that cause p-tau to concentrate in specific brain regions remain unclear. Here, we show that AQP4 polarization in the perivascular astrocytic end feet was impaired after TBI, which was most prominent in the ipsilateral brain tissue surrounding the directly impacted region and the contralateral hippocampal CA1 area and was accompanied by increased local p-tau, changes in dendritic spine density and morphology, and upregulation of the adenosine A2A receptor (A2AR). The critical role of the A2AR signaling in these pathological changes was confirmed by alleviation of the impairment of AQP4 polarity and accumulation of p-tau in the contralateral CA1 area in A2AR knockout mice. Given that p-tau can be released to the extracellular space and that the astroglial water transport via AQP4 is involved in tau clearance from the brain interstitium, our results suggest that regional disruption of AQP4 polarity following TBI may reduce the clearance of the toxic interstitial solutes such as p-tau and lead to changes in dendritic spine density and morphology. This may explain why TBI patients are more vulnerable to cognitive dysfunction.
format	article
author	Zi-Ai Zhao Ping Li Shi-Yang Ye Ya-Lei Ning Hao Wang Yan Peng Nan Yang Yan Zhao Zhuo-Hang Zhang Jiang-Fan Chen Yuan-Guo Zhou
author_facet	Zi-Ai Zhao Ping Li Shi-Yang Ye Ya-Lei Ning Hao Wang Yan Peng Nan Yang Yan Zhao Zhuo-Hang Zhang Jiang-Fan Chen Yuan-Guo Zhou
author_sort	Zi-Ai Zhao
title	Perivascular AQP4 dysregulation in the hippocampal CA1 area after traumatic brain injury is alleviated by adenosine A2A receptor inactivation
title_short	Perivascular AQP4 dysregulation in the hippocampal CA1 area after traumatic brain injury is alleviated by adenosine A2A receptor inactivation
title_full	Perivascular AQP4 dysregulation in the hippocampal CA1 area after traumatic brain injury is alleviated by adenosine A2A receptor inactivation
title_fullStr	Perivascular AQP4 dysregulation in the hippocampal CA1 area after traumatic brain injury is alleviated by adenosine A2A receptor inactivation
title_full_unstemmed	Perivascular AQP4 dysregulation in the hippocampal CA1 area after traumatic brain injury is alleviated by adenosine A2A receptor inactivation
title_sort	perivascular aqp4 dysregulation in the hippocampal ca1 area after traumatic brain injury is alleviated by adenosine a2a receptor inactivation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8b8e175757c444c9b2242f086186df40
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Perivascular AQP4 dysregulation in the hippocampal CA1 area after traumatic brain injury is alleviated by adenosine A2A receptor inactivation

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