title: Docosahexaenoic acid (DHA) prevents binge ethanol-dependent aquaporin-4 elevations while inhibiting neurodegeneration: experiments in rat adult-age entorhino-hippocampal slice cultures.
abstract: Repetitive binge intoxication with ethanol (alcohol) in adult rats, mimicking chronic ethanol abuse in alcoholics, causes trauma-like brain edema and relatively selective neurodegeneration of hippocampal dentate granule cells and pyramidal neurons in the temporal cortex (especially entorhinal cortex). We have now modeled the aspects of this type of acquired brain damage in vitro with rat entorhino-hippocampal slice cultures of adult brain age (62 ± 3 days). When sequentially treated (four 16-h overnight exposures) with 100 mM ethanol, the slices display elevated levels of aquaporin-4 (AQP4) water channels accompanied by significant neurodegeneration. Increased AQP4 has been associated with neuroinflammatory responses including edema, pro-inflammatory cytokine elevations, arachidonic acid release, and oxidative stress. Co-treatment of ethanol-binged slice cultures with docosahexaenoic acid (DHA), an omega-3 fatty acid known to suppress brain damage from other insults, prevents both the AQP4 elevations and the neurodamage. Surmising that AQP4 augmentation is a causative neuroinflammatory component in this model, we are investigating several possibilities to explain the protective actions of the omega-3 fatty acid. Since the worldwide incidence of cognitive dysfunction and dementia from ethanol abuse and alcoholism is not inconsequential, DHA supplementation with chronic alcoholics could emerge to be a rational approach to potentially lessening brain disabilities.
authors.affiliation: Department of Molecular Pharmacology & Therapeutics, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA. mcollin@lumc.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Collins
authors.forename: Kwan-Hoon
authors.initials: KH
authors.lastname: Moon
authors.forename: Nuzhath
authors.initials: N
authors.lastname: Tajuddin
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Neafsey
authors.forename: Hee-Yong
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000367:Age Factors; D000818:Animals; D051401:Aquaporin 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D063425:Binge Drinking / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004281:Docosahexaenoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051401:Aquaporin 4; D004281:Docosahexaenoic Acids; D000431:Ethanol