title: Impairments in hippocampal synaptic plasticity following prenatal ethanol exposure are dependent on glutathione levels.
abstract: Previous studies from our laboratory have shown that prenatal ethanol exposure (PNEE) causes a significant deficit in synaptic plasticity, namely long-term potentiation (LTP), in the dentate gyrus (DG) region of the hippocampus of male rats. PNEE has also been shown to induce an increase in oxidative stress and a reduction in antioxidant capacity in the brains of both male and female animals. In this study the interaction between LTP and the major antioxidant in the brain, glutathione (GSH), is examined. We show that depletion of the intracellular reserves of GSH with diethyl maleate (DEM) reduces LTP in control male, but not female animals, mirroring the effects of PNEE. Furthermore, treatment of PNEE animals with N-acetyl cysteine (NAC), a cysteine donor for the synthesis of GSH, increases GSH levels in the hippocampus and completely restores the deficits in LTP in PNEE males. These results indicate that in males GSH plays a major role in regulating LTP, and that PNEE may cause reductions in LTP by reducing the intracellular pool of this endogenous antioxidant.
authors.affiliation: Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, British Columbia, Canada; Department of Biology, University of Victoria, Victoria, British Columbia, Canada.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Patten
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Brocardo
authors.forename: Claire
authors.initials: C
authors.lastname: Sakiyama
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Wortman
authors.forename: Athena
authors.initials: A
authors.lastname: Noonan
authors.forename: Joana
authors.initials: J
authors.lastname: Gil-Mohapel
authors.forename: Brian R
authors.initials: BR
authors.lastname: Christie
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004558:Electric Stimulation; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage; D005978:Glutathione / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development / Q000473:pathology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000178:diet therapy / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002492:Central Nervous System Depressants; D016166:Free Radical Scavengers; D000431:Ethanol; D005978:Glutathione; D000111:Acetylcysteine
keywords: N-acetyl cysteine; dentate gyrus; diethyl maleate; fetal alcohol spectrum disorders; long-term potentiation; oxidative stress