The effects of isoflurane on the ratio of Bcl-2/Bax in rat fetal brain and spatial learning ability at juvenile age

Abstract

Objective To determine whether fetal rats exposure to isoflurane will cause postnatal learning and memory deficits,and change Bcl-2/Bax ratio in the hippocampus CA1 and retrosplenial cortex in fetal brain of rats. Methods Twenty-eight Sprague Dawley pregnant rats at gestation day 21 (E21) were randomly divided into isoflurane treatment group(n=14) and sham control group(n=14). Rats in isoflurane treatment group were ex-posed to 1.3% isoflurane in a carrying gas of 30% oxygen, balance nitrogen for 6 h in a warmed, humidified cham-ber. For sham control group,animals were treated at the same condition with only carrying gas. In behavior study,the spatial learning and memory ability at juvenile ages was determined with the Morris Water Maze(MWM). In immunohistochemistry study,changes of Bcl-2 and Bax expression in hippocampus CA1 and retrosplenial cortex in the fetus brain after isoflurane treatment at 2 hours was performed by using immunofluorecence staining.Results In the MWM training, the escape latency to platform in the place trials showed no significant difference between the two groups,but the postnatal rats in 1.3% isoflurane group showed obviously improved retention of memory by spending more percentage of time swimming in the probe quadrant as compared to the control animals ((42.33±2.31) s vs (33.2±2.15) s, t=2.21, P<0.05) in the probe test. Compared to controls, 1.3% isoflu-rane exposure for 6 h to the pregnant rats increased the intensity of Bcl-2, decreased the intensity of Bax, and sig-nificantly increased the Bcl-2/Bax ratio in the fetal hippocampal CA1 region (4.40±0. 86 vs 1.31±0.32, t=3. 378, P<0.01) and the fetal retrosplenial cortex (5.07±1.27 vs 1.47±0.48, t=2.656, P < 0.05) respec-tively. Conclusion 1.3% isoflurane exposure in pregnant rats significantly improves the spatial retention memo-ry of their rat pups at a juvenile age and increases the Bcl-2/Bax ratio in the hippocampal CA1 region and the ret-resplenial cortex in the fetal rat brains. Key words: Isoflurane; Brain; Fetus; Bcl-2,proto-oncogen protein; Bax,proto-oncogen protein; Cognition