出生前接触酒精对新生大鼠大脑发育中BDNF和TrkB的影响

Effects of prenatal alcohol exposure on BDNF and TrkB in cerebral cortex development of neonatal rats

[目的]探讨出生前接触酒精对新生大鼠大脑皮质发育中脑源性神经营养因子(BDNF)及其受体酪氨酸激酶受体B(TrkB)水平的影响.[方法]选择SD母鼠,酒精组母鼠每日摄取热量为35cal的酒精,正常对照组母鼠每日摄取与酒精组相等热量的奶粉(含质量分数为8%的糖),代理母组给予普通大鼠饲料.酒精组和正常对照组母鼠分娩6h后与其子鼠分开,麻醉后心脏采血,检测血液中乙醇和甲状腺素水平.酒精组及正常对照组新生子鼠由代理母组的代理母鼠养育,并分别于出生后0,7,14,21,28d(P0,P7,P14,P21,P28)时麻醉处死,采用免疫组织化学ABC染色法在大脑皮质中观察含有BDNF和TrkB的神经细胞的分布及形态,并采用ELISA法检测大脑中BDNF含量.[结果]酒精组母鼠血液中酒精水平明显高于正常对照组(P<0.05);而酒精组母鼠血液中甲状腺素含量显著低于正常对照组(P<0.05).正常对照组新生子鼠P7始在大脑皮质中可观察到长而明显突起的成熟的含有BDNF和TrkB的神经细胞;酒精组新生子鼠大脑皮质中始终未出现具有明显突起的成熟的含有BDNF和TrkB的神经细胞.酒精组新生子鼠出生后各时期大脑中BDNF蛋白含量均较正常对照组明显减少(P<0.05),P14时较正常对照组显著减少(P<0.000 1).[结论]大鼠母鼠孕期摄取酒精时引起血液中甲状腺素含量减少,还可导致其后代大脑皮质发育中BDNF和TrkB的合成障碍,进而导致大脑发育异常.

OBJECTIVE To study the effects of prenatal alcohol exposure on brain derived neurophic factor （BDNF） and tropomyosin receptor kinase B （TrkB） in cerebral cortex development of neonatal rats. METHODS Using the pregnant SD rats, alcohol group was taken in 35 calories of liquid alcohol every day, and control group was fed a liquid diet in which milk （containing 8% of sugar） replaced alcohol isocalorically, and surrogate group was fed with normal diet. The mother rats were separated with the neonatal rats within 6 hours after delivery in alcohol group and control group, and blood samples were obtained by cardiac puncture under anesthesia, and the plasma concentrations of alcohol and thyroxine were determined. The neonatal rats in alcohol and control groups were fostered by surrogate mother rats, and were executed with anesthesia at postnatal 0, 7, 14, 21 and 28 days, and the distribution and morphology of nerve cells containing BDNF and TrkB in cerebral cortex were observed by immunohistochemistry, and the content of BDNF was measured by ELISA. RESULTS The concentrations of blood alcohol and thyroxine was higher and lower in alcohol group dams than in control group dams（P〈0. 05）, respectively. The mature neurons with long and obvious protuberance containing BDNF and TrkB in cerebral cortex of neonatal rats began to be observed in control group at P7, and in contrast, the mature neurons with that were not found in alcohol group during early postnatal life from beginning to end. The contents of BDNF protein in brain of neonatal rats were significantly higher in alcohol group than in the control group during early postnatal life （P〈0.05）, especially at P14 （〈0. 000 1）. CONCLUSION When dams exposure to alcohol within gestation, not only the blood thyroxine concentration is significantly decreased, but also the synthesis of BDNF and TrkB are disordered in the development of cerebral cortex of offsprings leading to abnormal brain development.