母源性BDE-209暴露对子鼠海马GAP-43、BDNF表达的影响

Effect of maternal BDE-209 exposure on the expression of GAP-43 and BDNF in the hippocampus of the offspring rats

目的检测母源性BDE-209暴露对子鼠海马生长相关蛋白-43(GAP-43)、脑源性神经生长因子(BDNF)表达的影响,探讨母源性BDE-209神经发育毒性的可能机制。方法3月龄Wistar大鼠自妊娠0天起随机分为实验组A、B、C、D和对照组E,各实验组母鼠在妊娠期及哺乳期给予不同剂量BDE-209(100、300、600、1200mg/kg)胃灌,对照组胃灌等量花生油。21d子鼠断乳后各组随机选取10只雄性子鼠,用免疫组织化学法检测GAP-43、BDNF在子鼠海马的表达情况。结果实验组子鼠海马GAP-43表达下降,C、D组与E组比较差异有统计学意义(P=0.013,P=0.000),A、B组与E组比较差异无统计学意义(P=0.177,P=0.093)。实验组子鼠海马BDNF表达下降,B、C、D组与E组比较差异有统计学意义(P=0.033,P=0.005,P=0.001),A组和E组比较差异无统计学意义(P=0.066)。结论高剂量母源性BDE-209暴露可以降低子鼠海马GAP-43、BDNF的表达,导致神经元的生长、发育及信号传导障碍,影响神经系统发育,对神经系统功能的发挥造成损伤。

Objective To evaluate the effect of prenatal and lactational exposure to brominated diphenyl ethers-209 （BDE-209） on the expression of growth associated protein-43 （GAP-43） and brain-derived neurotrophic factors （BDNF） in the hippocampus of the offspring rats. Methods Peanut oil suspensions of commercial BDE-209 was administered daily at doses of 100, 300, 600, and 1200 mg/kg by oral gavage in pregnant Wistar rats （groups A, B, C, and D, respectively）. The control group （E） only received peanut oil of an equivalent volume. The hippocampus was isolated from 10 offspring rats in each group to determine the expression of GAP-43 and BDNF uisng immunohistochemistry. Results The GAP-43 in the BDE-209-treated groups were lower than that of the control group, and decreased with the increase of the dose of BDE-209 exposure. The groups C and D （P=0.013, P=0.000）, but not the groups A and B （P=0.177, P=0.093）, showed significant difference from the control group in GAP-43 expression. The positive expression of BDNF in the hippocampus was decreased as the exposure dose to BDE-209 increased, and significant differences were found between the groups B, C, D and the control group （P=0.033, P=0.005, P=0.001, respectively）, but not between group A and the control group （P=0.066）. Conclusion Maternal BDE-209 exposure can decrease the expression of GAP-43 and BDNF in the hippocampus of offspring rats, which may affect the axonal plasticity and regeneration of the neurons.