PMID- 28965835
OWN - NLM
STAT- MEDLINE
DCOM- 20180622
LR  - 20180622
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 365
DP  - 2017 Dec 4
TI  - Dopamine induces glutamate accumulation in astrocytes to disrupt neuronal 
      function leading to pathogenesis of minimal hepatic encephalopathy.
PG  - 94-113
LID - S0306-4522(17)30693-0 [pii]
LID - 10.1016/j.neuroscience.2017.09.040 [doi]
AB  - 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.
CI  - Copyright (c) 2017 IBRO. All rights reserved.
FAU - Ding, Saidan
AU  - Ding S
AD  - Zhejiang Provincial Key Laboratory of Aging and Neurological Disease Research, 
      Department of Surgery Laboratory, The First Affiliated Hospital of Wenzhou 
      Medical University, Wenzhou, Zhejiang 325000, China.
FAU - Wang, Xuebao
AU  - Wang X
AD  - Analytical and Testing Center, Wenzhou Medical University, Wenzhou, Zhejiang 
      325000, China.
FAU - Zhuge, Weishan
AU  - Zhuge W
AD  - Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang 325000, China.
FAU - Yang, Jianjing
AU  - Yang J
AD  - Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang 325000, China.
FAU - Zhuge, Qichuan
AU  - Zhuge Q
AD  - Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang 325000, China. Electronic address: 
      firstdsdan@163.com.
LA  - eng
PT  - Journal Article
DEP - 20170929
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (RNA, Small Interfering)
RN  - 075T165X8M (Thioacetamide)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Astrocytes/*drug effects
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Disease Models, Animal
MH  - Dopamine/*pharmacology
MH  - Excitatory Amino Acid Transporter 2/genetics/metabolism
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Glutamic Acid/*metabolism
MH  - Hepatic Encephalopathy/chemically induced/complications/*pathology
MH  - Maze Learning/drug effects
MH  - Microdialysis
MH  - Nerve Growth Factors/genetics/metabolism
MH  - Neurons/drug effects/*metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/physiology
MH  - Thioacetamide/toxicity
OTO - NOTNLM
OT  - Brain-Derived Nerve Growth Factor
OT  - dopamine
OT  - glutamate
OT  - minimal hepatic encephalopathy
OT  - neurotrophin-3
EDAT- 2017/10/03 06:00
MHDA- 2018/06/23 06:00
CRDT- 2017/10/03 06:00
PHST- 2017/04/08 00:00 [received]
PHST- 2017/09/20 00:00 [revised]
PHST- 2017/09/23 00:00 [accepted]
PHST- 2017/10/03 06:00 [pubmed]
PHST- 2018/06/23 06:00 [medline]
PHST- 2017/10/03 06:00 [entrez]
AID - S0306-4522(17)30693-0 [pii]
AID - 10.1016/j.neuroscience.2017.09.040 [doi]
PST - ppublish
SO  - Neuroscience. 2017 Dec 4;365:94-113. doi: 10.1016/j.neuroscience.2017.09.040. 
      Epub 2017 Sep 29.