Open Access

Elevated intracranial dopamine impairs the glutamate‑nitric oxide‑cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy

  • Authors:
    • Saidan Ding
    • Weilong Huang
    • Yiru Ye
    • Jianjing Yang
    • Jiangnan Hu
    • Xiaobin Wang
    • Leping Liu
    • Qin Lu
    • Yuanshao Lin
  • View Affiliations

  • Published online on: July 16, 2014     https://doi.org/10.3892/mmr.2014.2386
  • Pages: 1215-1224
  • Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.
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September-2014
Volume 10 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Ding S, Huang W, Ye Y, Yang J, Hu J, Wang X, Liu L, Lu Q and Lin Y: Elevated intracranial dopamine impairs the glutamate‑nitric oxide‑cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy. Mol Med Rep 10: 1215-1224, 2014.
APA
Ding, S., Huang, W., Ye, Y., Yang, J., Hu, J., Wang, X. ... Lin, Y. (2014). Elevated intracranial dopamine impairs the glutamate‑nitric oxide‑cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy. Molecular Medicine Reports, 10, 1215-1224. https://doi.org/10.3892/mmr.2014.2386
MLA
Ding, S., Huang, W., Ye, Y., Yang, J., Hu, J., Wang, X., Liu, L., Lu, Q., Lin, Y."Elevated intracranial dopamine impairs the glutamate‑nitric oxide‑cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy". Molecular Medicine Reports 10.3 (2014): 1215-1224.
Chicago
Ding, S., Huang, W., Ye, Y., Yang, J., Hu, J., Wang, X., Liu, L., Lu, Q., Lin, Y."Elevated intracranial dopamine impairs the glutamate‑nitric oxide‑cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy". Molecular Medicine Reports 10, no. 3 (2014): 1215-1224. https://doi.org/10.3892/mmr.2014.2386