DOPAMINE INDUCES GLUTAMATE ACCUMULATION IN ASTROCYTES TO DISRUPT NEURONAL FUNCTION LEADING TO PATHOGENESIS OF MINIMAL HEPATIC ENCEPHALOPATHY
DOPAMINE INDUCES GLUTAMATE ACCUMULATION IN ASTROCYTES TO DISRUPT NEURONAL FUNCTION LEADING TO PATHOGENESIS OF MINIMAL HEPATIC ENCEPHALOPATHY
复制标题
多巴胺诱导星形胶质细胞中谷氨酸积累，破坏神经元功能，导致轻微肝性脑病的发病机制
DOI：
10.1016/j.neuroscience.2017.09.040
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发表时间：
2017-12-04
期刊：
影响因子：
3.3
通讯作者：
Zhuge, Qichuan
中科院分区：
文献类型：
--
作者：
Ding, Saidan;Wang, Xuebao;Zhuge, Qichuan
颅内多巴胺（DA）升高可诱发轻微肝性脑病（MHE）。已知谷氨酸（Glu）毒性涉及许多神经系统疾病。在这项研究中，我们调查了DA是否增加Glu水平并与Glu合作损害记忆。我们发现DA上调TAAR 1，导致EAAT 2表达减少和Glu清除在原代皮质星形胶质细胞（PCA）。高DA增加TAAR 1表达，高Glu增加AMPAR表达，诱导CaN/NFAT信号传导的激活和原代皮质神经元（PCN）中BDNF（脑源性神经生长因子）/NT 3（神经营养因子-3）的产生减少。DA激活TAAR 1下调EAAT 2，并增加MHE细胞外Glu水平。此外，DA和Glu一起通过激活MHE中的CaN/NFAT信号引起神经元BDNF/NT 3的产生减少和记忆障碍。从这些发现中，我们得出结论，DA通过与TAAR 1相互作用和破坏星形胶质细胞中的EAAT 2信号传导来增加Glu水平，并且DA与TAAR 1相互作用和Glu与AMPAR相互作用通过激活CaN/NFAT信号传导来协同降低BDNF的产生，从而损害MHE大鼠的记忆。(C)2017年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Minimal hepatic encephalopathy (MHE) is Induced by elevated intracranial dopamine (DA). Glutamate (Glu) toxicity is known to be involved In many neurological disorders. In this study, we investigated whether DA increased Glu levels and collaborated with Glu to impair memory. We found that DA upregulated TAAR1, leading to reduced EAAT2 expression and Glu clearance in primary cortical astrocytes (PCAs). High DA increased TAAR1 expression, and high Glu Increased AMPAR expression, inducing the activation of CaN/NFAT signaling and a decrease in the production of BDNF (Brain Derived Nerve Growth Factor)/NT3 (neurotrophin-3) in primary cortical neurons (PCNs). DA activated TAAR1 to downregulate EAAT2 and increase extracellular Glu levels in MHE. Additionally, DA together with Glu caused decreased production of neuronal BDNF/NT3 and memory impairment through the activation of CaN/NFAT signaling in MHE. From these findings, we conclude that DA Increases Glu levels via interaction with TAAR1 and disruption of EAAT2 signaling in astrocytes, and DA interacting with TAAR1 and Glu interacting with AMPAR synergistically decreased the production of BDNF by activation of CaN/NFAT signaling to impair memory in MHE rats. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.