Effects of prenatal exposure to ethanol on the expression of bcl-2, bax and caspase 3 in the developing rat cerebral cortex and thalamus.
Prenatal exposure to ethanol causes neuronal death in somatosensory cortex, but apparently not in the ventrobasal nucleus of the thalamus. Effectors such as bcl-2, bax, and caspase 3 can determine whether a neuron survives or dies. We hypothesize that ethanol differentially affects the expression of these proteins in the cortex and thalamus during the periods of naturally occurring and ethanol-induced neuronal death. Pregnant rats were fed ad libitum with an ethanol-containing liquid diet (Et) or pair-fed an isocaloric non-alcoholic diet (Ct). Samples were collected from fetuses (gestational day (G) 16 and G19) and pups (postnatal day (P) 0 through P30) and examined for bcl-2, bax, or caspase 3 expression using a quantitative immunoblotting procedure. Prenatal exposure to ethanol reduced cortical bcl-2 expression, but not bax expression on P6. Hence, the bcl-2/bax ratio was lower in Et-treated rats than in controls. In contrast, thalamic expression of neither bcl-2 nor bax was significantly different in the two groups of rats. Thus, the thalamic bcl-2/bax ratio was unaffected by exposure to ethanol. During the period of naturally occurring neuronal death, the expression of the active (20 kDa) and inactive isoforms (32 kDa) of caspase 3 was altered in the cortices of Et-treated rats, but not in their thalami. Thus, prenatal exposure to ethanol affected the early postnatal expression of death-related proteins in the cortex, but not in the thalamus. These biochemical changes concur with anatomical data on the spatial and temporal selectivity of ethanol toxicity in the developing CNS.
Mooney
S M
SM
Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA 52242-1000, USA.
Miller
M W
MW
D000375:Aging / Q000187:drug effects / Q000502:physiology; D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013788:Thalamus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000431:Ethanol; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases