15 December 2017
Int J Med Sci 2008; 5(6):295-302. doi:10.7150/ijms.5.295
Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain
Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, California 92350, USA
Cocaine abuse during pregnancy has been associated with numerous adverse perinatal outcomes. Aims: The present study was to determine whether prenatal cocaine exposure induced apoptosis and the possible role of Bcl-2 family genes in the programming cell death in fetal rat brain. Main methods: Pregnant rats were treated with cocaine subcutaneously (30 & 60 mg/kg/day) from day 15 to 21 of gestation. Then the fetal and maternal brains were isolated. Key findings: Cocaine produced a dose-dependent decrease in fetal brain weight and brain/body weight ratio (P<0.05). Apoptotic nuclei in fetal brain were increased from 2.6 ± 0.1 (control) to 8.1± 0.6 (low dose) and 10.4 ± 0.2% (high dose) (P<0.05). In accordance, cocaine dose dependently increased activities of caspase-3, caspase-8, and caspase-9 (% of control) in the fetal brain by 177%, 155%, 174%, respectively, at 30 mg/kg/day, and by 191%, 176%, 274%, respectively, at 60 mg/kg/day. In contrast, cocaine showed no effect on caspase activities in the maternal brain. Cocaine produced a dose-dependent increase in both Bcl-2 and Bax protein expression in the fetal brain, and increased the ratio of Bax/Bcl-2 at dose of 30 mg/kg/day (P<0.05). Significance: Our study has demonstrated that prenatal cocaine exposure induces apoptosis in the fetal brain, and suggested that up-regulating Bax/Bcl-2 gene expression may be involved in cocaine-induced apoptosis. The increased apoptosis of neuronal cells in the fetal brain is likely to play a key role in cocaine-induced neuronal defects during fetal development.
Keywords: cocaine, fetus, brain, apoptosis, caspase, Bcl-2 proteins
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How to cite this article:
Xiao D, Zhang L. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain. Int J Med Sci 2008; 5(6):295-302. doi:10.7150/ijms.5.295. Available from http://www.medsci.org/v05p0295.htm