LONG-TERM ALCOHOL EXPOSURE ELICITS HIPPOCAMPAL NONSYNAPTIC EPILEPTIFORM ACTIVITY CHANGES ASSOCIATED WITH EXPRESSION AND FUNCTIONAL CHANGES IN NKCC1, KCC2 CO-TRANSPORTERS AND NA(+)/K+-ATPase

LONG-TERM ALCOHOL EXPOSURE ELICITS HIPPOCAMPAL NONSYNAPTIC EPILEPTIFORM ACTIVITY CHANGES ASSOCIATED WITH EXPRESSION AND FUNCTIONAL CHANGES IN NKCC1, KCC2 CO-TRANSPORTERS AND NA(+)/K+-ATPase

Author Santos, Luiz E. C. Google Scholar
Rodrigues, Antonio M. Google Scholar
Lopes, Mariana R. Google Scholar
Costa, Victor D. C. Google Scholar
Scorza, Carla A. Autor UNIFESP Google Scholar
Scorza, Fulvio A. Autor UNIFESP Google Scholar
Cavalheiro, Esper A. Autor UNIFESP Google Scholar
Almeida, Antonio-Carlos G. Google Scholar
Abstract Nonsynaptic mechanism changes, particularly the enhancement of NKCC1 expression in the dentate gyrus (DG) after 4 weeks of ethanol consumption, motivate the present work, in which rats were submitted to a period of chronic consumption (12 weeks). Four groups of six animals (6-week-old male Wistar rats) were formed, including the control (C), ethanol 1 (El), ethanol 2 (E2) and ethanol 3 (E3) groups. The rats in the El, E2 and E3 groups were treated daily with a 30% v/v solution of ethanol, administered via oral gavage (1.0, 2.0 and 3.0 g/kg, respectively). Nonsynaptic epileptiform activities (NEA) were induced by means of the zero-Ca2+ and high-K+ model using hippocampal slices and were recorded in the DG. The presence of NKCC1, KCC2, a1Na(+)/K+-ATPase and GFAP immunoreactivity was analyzed. The results demonstrate that alcohol consumption changes NEA, and these changes are more prominent at the lower dosage. An increase in the DC shifts associated with epileptiform discharges was present with the low dose. This increase was correlated with the increment of NKCC1 expression. Confocal microscopy images indicate the NKCC1 increase was pronounced in the initial axonal segment of granule cells. The blockage of these cotransporters during NEA induction with bumetanide suppressed the DC shift increase and diminished all parameters of NEA that were quantified for all groups treated with ethanol. Therefore, the increase in NKCC1 expression and the effective activity of this cotransporter, which were observed in the treated groups, suggest that drugs that act for block NKCC1 represent promising strategies for diminishing the effects of alcohol damage on the brain. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Keywords epilepsy
electrophysiology
immunohistochemistry
dentate gyrus
ethanol
xmlui.dri2xhtml.METS-1.0.item-coverage Oxford
Language English
Sponsor Fapemig (Fundacao de Amparo a Pesquisa do Estado de Minas Gerais)
CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)
CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
Date 2017
Published in Neuroscience. Oxford, v. 340, p. 530-541, 2017.
ISSN 0306-4522 (Sherpa/Romeo, impact factor)
Publisher Pergamon-Elsevier Science Ltd
Extent 530-541
Origin http://dx.doi.org/10.1016/j.neuroscience.2016.11.015
Access rights Closed access
Type Article
Web of Science ID WOS:000392039800045
URI https://repositorio.unifesp.br/handle/11600/55267

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