Effects of chronic prenatal ethanol exposure on mitochondrial glutathione and 8-iso-prostaglandin F2α concentrations in the hippocampus of the perinatal guinea pig
C. R. Green A B , L. T. Watts C , S. M. Kobus A , G. I. Henderson C D , J. N. Reynolds A B and J. F. Brien A B E
+ Author Affiliations
- Author Affiliations
A Department of Pharmacology and Toxicology, Queen’s University, Kingston, ON K7L 3N6, Canada.
B Centre for Neuroscience Studies, Queen’s University, Kingston, ON K7L 3N6, Canada.
C Department of Pharmacology, The University of Texas Health Science Centre, San Antonio, TX 78229-3900, USA.
D Department of Medicine–Division of Gastrointestinal/Nutrition, The University of Texas Health Science Centre, San Antonio, TX 78229-3900, USA.
E Corresponding author. Email: brienj@post.queensu.ca
Reproduction, Fertility and Development 18(5) 517-524 https://doi.org/10.1071/RD05128
Submitted: 3 October 2005 Accepted: 22 February 2006 Published: 8 May 2006
Abstract
It is hypothesised that oxidative stress is a key mechanism of ethanol neurobehavioural teratogenicity, resulting in altered endogenous antioxidant status and increased membrane lipid peroxidation in the hippocampus of chronic prenatal ethanol exposure (CPEE) offspring. To test this hypothesis, timed pregnant guinea-pigs (term, approximately gestational day (GD) 68) received chronic daily oral administration of (i) 4 g ethanol kg–1 maternal bodyweight, (ii) isocaloric sucrose with pair feeding, or (iii) water. At GD 65 (term fetus) and postnatal day (PD) 0 (neonate), individual offspring were killed, the brain was excised and the hippocampi were dissected. Glutathione (GSH) concentration was measured in the cytosolic and mitochondrial fractions of hippocampal homogenate. The occurrence of lipid peroxidation was determined by measuring the concentration of 8-iso-prostaglandin F2α (8-iso-PGF2α). There was CPEE-induced decreased brain weight and hippocampal weight at GD 65 and PD 0, decreased mitochondrial GSH concentration in the hippocampus at PD 0, with no change in mitochondrial GSH concentration at GD 65 or cytosolic GSH concentration at GD 65 or PD 0, and no change in mitochondrial or whole-homogenate 8-iso-PGF2α concentration in the hippocampus at GD 65 or PD 0. The data demonstrate that CPEE produces selective mitochondrial dysfunction in the hippocampus of the neonatal guinea-pig, involving GSH depletion.
Acknowledgments
This research was supported by operating grants from the Canadian Institutes of Health Research (NET-54014) and the National Institute on Alcohol Abuse and Alcoholism (RO-5R21 AA013431). CRG is the recipient of a provincial Ontario Graduate Scholarship in Science and Technology.
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