镧对断乳后仔鼠大脑皮质CREB磷酸化和BDNF表达的影响
Effects of Lanthanum on CREB Phosphorylation and BDNF Expression in Cerebral Cortex of Rats after Weaning
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摘要:
目的 研究镧(lanthanum, La)对断乳后仔鼠大脑皮质环磷酸腺苷反应元件结合蛋白(cAMP response element binding protein, CREB)磷酸化和脑源性神经营养因子(brain derived neurotrophic factor, BDNF)表达的影响。 方法 40只成年雌性Wistar大鼠随机分为对照和低、中、高剂量La染毒组,各La染毒组孕鼠产仔后分别饮用0.25%、0.5%和1.0% LaCl3溶液,其仔鼠断乳前吸吮各自母乳染LaCl3,断乳后饮用0.25%、0.5%和1.0% LaCl3染毒1个月,然后进行水迷宫测试,并测定大脑皮质La含量、CREB磷酸化、BDNF mRNA和蛋白表达水平。 结果 水迷宫测试时,低、中剂量La染毒组仔鼠错误次数和潜伏期明显高于对照组,高剂量La染毒组仔鼠错误次数和潜伏期明显高于对照和低剂量La染毒组。La染毒剂量与仔鼠大脑皮质中的蓄积量呈正相关(r=0.954)与皮质BNDF mRNA、蛋白表达呈负相关(r=-0.976,r=-0.952)。 结论 La损害断乳后仔鼠的学习记忆能力,其机制可能与La致大脑皮质CREB磷酸化和BDNF基因转录和蛋白表达水平降低有关。 Abstract:Objective To study effects of lanthanum (La) on cAMP response element binding protein (CREB) phosphorylation and brain derived neurotrophic factor (BDNF) expression in cerebral cortex of rats after weaning. Methods Forty female rats were divided randomly into four groups:control,low-,medium-,and high-dose La-administrated groups.Pregnant rats in La-administrated groups were administrated with 0.25%,0.5% and 1.0% LaCl3 in drinking water after delivery,respectively.The offspring of the La-administrated groups were given to LaCl3 by respective parental lactation before weaning,and then were administrated with 0.25%,0.5% and 1.0% LaCl3 in drinking water for one month respectively.Learning and memory of the pups were measured by water maze test.La contents,CREB phosphorylation,BDNF mRNA and protein expression in the cerebral cortex of offspring were also detected. Results In the water maze test,the error counts and the latency of the low-and medium-dose La-administrated groups were significantly higher than those of the control group,and the pattern was also observed in the high-dose La-administrated group as compared with the control and the low-dose La-administrated groups.The exposure level of La correlated with the La contents in the cerebral cortex positively (r=0.954) but with BDNF mRNA expression and BDNF protein expression negatively (r=-0.976,r=-0.952,respectively). Conclusion La may induce impairments of learning and memory in rats after weaning,which is possibly related to lower levels of CREB phosphorylation,BDNF gene transcription and protein expression caused by La exposure.
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