镧影响大鼠海马CaMKIV、CREB磷酸化和BDNF基因表达的研究  

Study of the effects of lanthanum on hippocampal CaMKIV,CREB phosphorylation and BDNF expression in rats

作　　者：杨敬华[1] 刘秋芳[1] 巫生文[1] 张立丰[1] 齐鸣[1] 鲁帅[1] 蔡原[1] 

机构地区：[1]中国医科大学公共卫生学院卫生毒理学教研室,辽宁沈阳110001

出　　处：《毒理学杂志》2010年第4期263-267,共5页Journal of Toxicology

基　　金：国家自然科学基金(30800925);辽宁省科技厅基金(2005225008-3)

摘　　要：目的研究镧对大鼠海马钙调蛋白依赖性蛋白激酶(CaMKIV)、环磷酸腺苷反应元件结合蛋白(CREB)磷酸化和脑源性神经营养因子(BDNF)基因表达的影响,探讨镧损害学习记忆能力的机制。方法随机将Wistar雌性成年大鼠分成对照组和低、中、高剂量染镧组,低、中、高剂量染镧组孕鼠在产仔后分别饮用0.25%、0.5%和1.0%LaCl3溶液。各染镧组仔鼠在断乳前经吸吮母乳染镧,断乳后自行饮用0.25%、0.5%和1.0%LaCl3溶液染镧1个月。然后对仔鼠进行水迷宫和跳台试验,并测定仔鼠海马镧含量、CaMKIV和CREB磷酸化以及BDNF mRNA表达水平。结果水迷宫和跳台测试时,各染镧组仔鼠的学习记忆能力明显低于对照组,呈一定的剂量-效应关系。染镧组仔鼠海马镧含量显著高于对照组,且随染毒剂量增加而增加。中、高剂量染镧组仔鼠海马CaMKIV、CREB磷酸化以及BDNF mRNA表达水平显著低于对照和低剂量染镧组。结论在该试验条件下,镧损害大鼠学习记忆能力的机制可能与海马CaMKIV、CREB磷酸化和BDNF基因表达水平下降有关。Objective To study the effects of lanthanum（La） on hippocampal CaMKIV,CREB phosphorylation and BDNF expression in rats,and discuss the mechanism underlying the learning and memory impairments induced by La.Methods Wistar female adult rats were divided randomly into four groups： control,low-,middle-,and high-dose La groups.Low-,middle-,and high-dose La groups of pregnant rats were administrated with 0.25%,0.5%,1.0% LaCl3 in drinking water,respectively.Pups of La groups were administrated with La by lactation from birth to weaning.After weaning,pups of La groups were administrated with 0.25%,0.5%,1.0% LaCl3 in drinking water for one month,respectively.Learning and memory of pups were measured by water maze and jumping stand tests.La contents,phosphorylated CaMKIV,CREB and BDNF mRNA expression in the hippocampus of pups were also detected.Results In the water maze and jumping stand tests,learning and memory of three La groups were significantly weaker than those of control group,and present dose-effect relationship to some extent.La contents in the hippocampus of three La groups were significantly higher than those of control group,and increased with administrated-dose increasing.The levels of phosphorylated CaMKIV and CREB protein and BDNF mRNA expression in the hippocampus of middle,high-dose La groups were significantly lower than those of control and low-dose La groups.Conclusion The learning and memory impairments caused by La may be associated with decreased levels of hippocampal CaMKIV,CREB phosphorylation and BDNF transcription expression.

关 键 词：镧 海马 学习记忆 

分 类 号：R744.8[医药卫生—神经病学与精神病学]