Chronic prenatal ethanol exposure increases apoptosis in the hippocampus of the term fetal guinea pig.
It is hypothesized that chronic prenatal ethanol exposure (CPEE), via maternal ethanol administration, increases mitochondrial-directed apoptosis in the hippocampus of the term fetus that precedes loss of hippocampal CA1 pyramidal cells. To test this hypothesis, timed pregnant guinea pigs received chronic oral administration of: 4 g ethanol/kg maternal body weight/day, isocaloric-sucrose/pair-feeding or water throughout gestation. At gestational day 65 (term fetus) and postnatal day 0 (neonate), individual offspring were euthanized, and the brain was excised and dissected. CPEE, compared with the isocaloric-sucrose/pair-fed and water control groups, decreased the brain weight of the term fetus and neonate. CPEE did not alter the density of CA1 pyramidal cells in the hippocampus of the term fetus and neonate. In the term fetus, CPEE increased cytochrome c content in the cytosolic fraction of the hippocampus, altered the mitochondrial localization of cytochrome c in cells of the dorsal hippocampus, and increased the percentage of cells in the dorsal hippocampus containing activated caspase-3 and cleaved poly(ADP-ribose) polymerase. The data indicate that CPEE increases neuroapoptosis in the hippocampus of term fetus, which appears to occur via an intrinsic, mitochondrial-directed mechanism initiated by leakage of pro-apoptotic cytochrome c from mitochondria into the cytoplasm.
Green
C R
CR
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Kobus
S M
SM
Ji
Y
Y
Bennett
B M
BM
Reynolds
J N
JN
Brien
J F
JF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis; D045304:Cytochromes c / Q000032:analysis; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D005333:Fetus / Q000187:drug effects; D006168:Guinea Pigs; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects*; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D011247:Pregnancy; D017966:Pyramidal Cells / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
D000431:Ethanol; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3