Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain

• Main Author: DaLiao Xiao, Lubo Zhang
• Format: Article
• Language: English
• Published: Ivyspring International Publisher 2008-01-01
• Series: International Journal of Medical Sciences
• Online Access: http://www.medsci.org/v05p0295.htm

<p>Cocaine abuse during pregnancy has been associated with numerous adverse perinatal outcomes. <b>Aims: </b>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. <b>Main methods:</b> Pregnant rats were treated with cocaine subcutaneously (30 &#38; 60 mg/kg/day) from day 15 to 21 of gestation. Then the fetal and maternal brains were isolated. <b>Key findings:</b> Cocaine produced a dose-dependent decrease in fetal brain weight and brain/body weight ratio (P&#60;0.05). Apoptotic nuclei in fetal brain were increased from 2.6 &#177; 0.1 (control) to 8.1&#177; 0.6 (low dose) and 10.4 &#177; 0.2% (high dose) (P&#60;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&#60;0.05). <b>Significance: </b>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.</p>