title: Elevated intracranial dopamine impairs the glutamate‑nitric oxide‑cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy.
abstract: In a previous study by our group memory impairment in rats with minimal hepatic encephalopathy (MHE) was associated with the inhibition of the glutamate‑nitric oxide‑cyclic guanosine monophosphate (Glu‑NO‑cGMP) pathway due to elevated dopamine (DA). However, the effects of DA on the Glu‑NO‑cGMP pathway localized in primary cortical astrocytes (PCAs) had not been elucidated in rats with MHE. In the present study, it was identified that when the levels of DA in the cerebral cortex of rats with MHE and high‑dose DA (3 mg/kg)‑treated rats were increased, the co‑localization of N‑methyl‑d‑aspartate receptors subunit 1 (NMDAR1), calmodulin (CaM), nitric oxide synthase (nNOS), soluble guanylyl cyclase (sGC) and cyclic guanine monophosphate (cGMP) with the glial fibrillary acidic protein (GFAP), a marker protein of astrocytes, all significantly decreased, in both the MHE and high‑dose DA‑treated rats (P<0.01). Furthermore, NMDA‑induced augmentation of the expression of NMDAR1, CaM, nNOS, sGC and cGMP localized in PCAs was decreased in MHE and DA‑treated rats, as compared with the controls. Chronic exposure of cultured cerebral cortex PCAs to DA treatment induced a dose‑dependent decrease in the concentration of intracellular calcium, nitrites and nitrates, the formation of cGMP and the expression of NMDAR1, CaM, nNOS and sGC/cGMP. High doses of DA (50 µM) significantly reduced NMDA‑induced augmentation of the formation of cGMP and the contents of NMDAR1, CaM, nNOS, sGC and cGMP (P<0.01). These results suggest that the suppression of DA on the Glu‑NO‑cGMP pathway localized in PCAs contributes to memory impairment in rats with MHE.
authors: 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, P.R. China.
authors: Saidan
authors: S
authors: Ding
authors: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors: Weilong
authors: W
authors: Huang
authors: Department of Computer, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors: Yiru
authors: Y
authors: Ye
authors: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors: Jianjing
authors: J
authors: Yang
authors: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors: Jiangnan
authors: J
authors: Hu
authors: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors: Xiaobin
authors: X
authors: Wang
authors: 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, P.R. China.
authors: Leping
authors: L
authors: Liu
authors: Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors: Qin
authors: Q
authors: Lu
authors: First Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors: Yuanshao
authors: Y
authors: Lin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001522:Behavior, Animal; D002147:Calmodulin / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000503:physiopathology*; D008568:Memory / Q000187:drug effects; D016202:N-Methylaspartate / Q000009:adverse effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase
chemical_list: D002147:Calmodulin; D006152:Cyclic GMP; D004298:Dopamine; D005904:Glial Fibrillary Acidic Protein; D005971:Glutamates; D006162:Guanylate Cyclase; D016202:N-Methylaspartate; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D018160:Receptors, Cytoplasmic and Nuclear; D016194:Receptors, N-Methyl-D-Aspartate; D000071756:Soluble Guanylyl Cyclase