Ethanol withdrawal is required to produce persisting N-methyl-D-aspartate receptor-dependent hippocampal cytotoxicity during chronic intermittent ethanol exposure

Alcohol
Anna R ReynoldsMark A Prendergast

Abstract

Chronic intermittent ethanol consumption is associated with neurodegeneration and cognitive deficits in preclinical laboratory animals and in the clinical population. While previous work suggests a role for neuroadaptations in the N-methyl-d-aspartate (NMDA) receptor in the development of ethanol dependence and manifestation of withdrawal, the relative roles of ethanol exposure and ethanol withdrawal in producing these effects have not been fully characterized. To examine underlying cytotoxic mechanisms associated with chronic intermittent ethanol (CIE) exposure, organotypic hippocampal slices were exposed to 1-3 cycles of ethanol (50 mM) in cell culture medium for 5 days, followed by 24 h of ethanol withdrawal, in which a portion of slices were exposed to competitive NMDA receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV; 40 μM). Cytotoxicity was assessed using immunohistochemical labeling of neuron-specific nuclear protein (NeuN; Fox-3), a marker of mature neurons, and thionine (2%) staining of Nissl bodies. Multiple cycles of CIE produced neurotoxicity, as reflected in persisting losses of neuron NeuN immunoreactivity and thionine staining in each of the primary cell layers of the hippocampal formation. Hippocampi ...Continue Reading

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Citations

Feb 24, 2016·Frontiers in Molecular Neuroscience·Michael A Collins, Edward J Neafsey
Nov 20, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·C E Van SkikeK Nixon
Apr 4, 2016·Alcoholism, Clinical and Experimental Research·Elisabetta GeraceDomenico E Pellegrini-Giampietro
Mar 9, 2017·Alcoholism, Clinical and Experimental Research·Colleen J Lawrimore, Fulton T Crews
Jan 18, 2018·The Journal of Pharmacology and Experimental Therapeutics·Nuzhath TajuddinMichael A Collins
Feb 15, 2020·Alcoholism, Clinical and Experimental Research·Linda Patia Spear
Jun 3, 2018·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Lawrence Siu-Chun LawTong Joo Gan
May 9, 2018·Neuroscience and Biobehavioral Reviews·Jérôme JeanblancMickael Naassila

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