脑发育期缺碘对大鼠学习记忆功能的影响
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摘要
目的探讨脑发育期缺碘对大鼠学习记忆功能的影响。方法大鼠饮用含质量浓度为0.3 g/L甲硫咪唑的自来水诱发脑发育不同时期缺碘大鼠模型,E1组为胚胎期缺碘模型鼠,P1组为出生后1~50 d缺碘模型鼠,P30组为出生后30~50 d缺碘模型鼠,N组为正常对照鼠。观察其子代大鼠的行为学改变,利用放免法测定大鼠血清游离三碘甲腺原氨酸(FT3)和四碘甲腺原氨酸(FT4)水平,采用HE染色及TUNEL法观察大鼠的脑组织形态学改变。结果 P30组的血清游离FT3和FT4水平显著低于N组,差异有统计学意义(P<0.05)。"Y"迷宫实验结果显示,P1和P30组的正确反应率显著低于N组,差异有统计学意义(P<0.05)。P1组的达标所需天数显著多于N组,差异有统计学意义(P<0.05)。P1组的记忆保持率显著低于N组,差异有统计学意义(P<0.05)。P1组的正确反应率、记忆保持率显著低于E1组,达标所需天数显著多于E1组,差异有统计学意义(P<0.05)。P1组的正确反应率显著低于P30组,达标所需天数显著多于P30组,差异有统计学意义(P<0.05)。P1组和P30组的皮质细胞凋亡数显著多于N组,差异有统计学意义(P<0.05)。P1组的皮质、海马细胞凋亡数显著多于E1组和P30组,差异有统计学意义(P<0.05)。P1组的小脑细胞凋亡数显著多于E1组,差异有统计学意义(P<0.05)。结论脑发育时期缺碘能够导致大鼠学习记忆功能发育障碍,其发生与脑组织细胞凋亡增多有关。
Objective To explore the influence of iodine deficiency in brain development on rat′s learning and memory functions. Methods Iodine deficiency models of rats in different periods of brain development were induced by drinking tap water containing 0.3 g/L thiamazole.Iodine deficiency of model rat in embryonic period was classified into E1 group,iodine deficiency of model rats 1 to 50 d and 30 to 50 d after birth were named as P1 group and P30 group respectively,and normal control group was set as N group.Change of behavioristics in offspring rats was observed.Serum free triiodothryonine(FT3) and free thyroxine or tetraiodothyronine(FT4) was determined by radioimmunoassay respectively.Morphological change of rat′s brain tissue was observed by HE staining and TUNEL. Results The level of serum FT3 and FT4in P30 group was lower than that in E1 group and P1 group,with significant difference(P <0.05).In the "Y"maze experiments,the rate of correct response in P1 group and P30 group N group was lower than that in N group,with significant difference(P<0.05).The days of reachting the standards in P1 group was more than that in N group,with significant difference(P<0.05).The rate of memory retention in P1 group was lower than that in N group,with significant difference(P<0.05).The rate of correct response and memory retention in P1 group was lower than that in E1 group,with significant difference(P<0.05).The days of reachting the standards in P1 group was more than that in E1 group,with significant difference(P<0.05).The rate of correct response in P1 group was lower than that in P30 group,with significant difference(P<0.05).The days of reachting the standards in P1 group was more than that in P30 group,with significant difference(P <0.05).The apoptosis number of cerebral cortex cell in P1 group and P30 group was more than that in N group,with significant difference(P<0.05).The apoptosis number of cerebral cortex and hippocampus cell was more than that in E1 group and P30 group,with significant difference(P<0.05).The apoptosis number of cerebellum cell was more than that in E1 group,with significant difference(P<0.05). Conclusion Iodine deficiency in brain development can lead to disorders of learning and memory functions in rats,which is probably related with apoptosis of brain tissue.
Objective To explore the influence of iodine deficiency in brain development on rat′s learning and memory functions. Methods Iodine deficiency models of rats in different periods of brain development were induced by drinking tap water containing 0.3 g/L thiamazole.Iodine deficiency of model rat in embryonic period was classified into E1 group,iodine deficiency of model rats 1 to 50 d and 30 to 50 d after birth were named as P1 group and P30 group respectively,and normal control group was set as N group.Change of behavioristics in offspring rats was observed.Serum free triiodothryonine(FT3) and free thyroxine or tetraiodothyronine(FT4) was determined by radioimmunoassay respectively.Morphological change of rat′s brain tissue was observed by HE staining and TUNEL. Results The level of serum FT3 and FT4in P30 group was lower than that in E1 group and P1 group,with significant difference(P <0.05).In the "Y"maze experiments,the rate of correct response in P1 group and P30 group N group was lower than that in N group,with significant difference(P<0.05).The days of reachting the standards in P1 group was more than that in N group,with significant difference(P<0.05).The rate of memory retention in P1 group was lower than that in N group,with significant difference(P<0.05).The rate of correct response and memory retention in P1 group was lower than that in E1 group,with significant difference(P<0.05).The days of reachting the standards in P1 group was more than that in E1 group,with significant difference(P<0.05).The rate of correct response in P1 group was lower than that in P30 group,with significant difference(P<0.05).The days of reachting the standards in P1 group was more than that in P30 group,with significant difference(P <0.05).The apoptosis number of cerebral cortex cell in P1 group and P30 group was more than that in N group,with significant difference(P<0.05).The apoptosis number of cerebral cortex and hippocampus cell was more than that in E1 group and P30 group,with significant difference(P<0.05).The apoptosis number of cerebellum cell was more than that in E1 group,with significant difference(P<0.05). Conclusion Iodine deficiency in brain development can lead to disorders of learning and memory functions in rats,which is probably related with apoptosis of brain tissue.
引文
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[17]随力,任杰.甲状腺激素在脑学习和记忆功能中的作用[J].中国药理学通报,2010,26(11):1538-1540.
[18]Gilbert ME,Sui L.Dose-dependent reductions in spatial learning and synaptic function in the dentate gyrus of adult rats following developmental thyroid hormone insufficiency[J].Brain Res,2006,1069(1):10-22.
[19]Alzoubi KH,Gerges NZ,Aleisa AM,et al.Levothyroxin restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory:Behavioral,electrophysiological,and molecular studies[J].Hippocampus,2009,19(1):66-78.
[20]刘连杰,殷洪博,王萍,等.碘缺乏甲状腺功能减退对仔鼠海马LTP的影响[J].中国公共卫生,2005,21(6):701-702.
[2]李娟,王瑞英.甲状腺机能减退与脑发育[J].国际内科学杂志,2007,34(4):228-231.
[3]马泰,卢倜章,于志恒.碘缺乏病[M].北京:人民卫生出版社,1993:325-326.
[4]Reid RE,Kim EM,Page D,et al.Thyroxine replacement in an animal model of congenitl hypothyr oidism[J].Physiol Behav,2007,91(223):299-303.
[5]黄新文,李筠,季钗,等.围生期甲状腺功能低下对仔鼠运动与学习记忆的影响[J].中华儿科杂志,2007,45(3):221-222.
[6]黄新文,赵正言,季钗.甲状腺功能低下对新生期大鼠海马神经元凋亡及Bcl-2、Bax基因表达的影响[J].中华儿科杂志,2005,43(1):48-52.
[7]何斯纯,何剑琴,周丽丽.脑发育期甲状腺功能低下大鼠脑干听觉诱发电位的变化[J].暨南大学学报·医学版,2006,27(4):519-524.
[8]李华娇,何斯纯.脑发育期甲状腺功能低下对大鼠脑功能的影响[J].暨南大学学报·医学版,2013,34(2):144-149.
[9]李华娇.脑发育期甲状腺功能低下对大鼠脑功能的影响[D].广州:暨南大学,2013.
[10]朱德发.亚临床型甲状腺功能减退症的认知损伤机制和替代治疗的价值[D].合肥:安徽医科大学,2006.
[11]Simard M,van Reekum R.Memory assessment in studies of cognition-enhancing drugs for Alzheimers′disease[J].Drugs Aging,1999,14(3):197-230.
[12]王道年,刘春蕾,朱德发.甲状腺素对原发性甲状腺功能减退症认知功能损害的治疗效果[J].中国临床保健杂志,2009,12(2):117-118.
[13]尹益勇,刘妮,李华娇,等.脑发育期甲状腺激素对大鼠听觉中潜伏期反应和学习记忆的影响[J].暨南大学学报·医学版,2011,32(2):165-170.
[14]季钗,黄新文,杨荣旺,等.围生期甲低大鼠行为发育及其与海马AR m RNA表达的相关性研究[J].浙江大学学报·医学版,2008,37(3):283-288.
[15]French PJ,O′Connor V,Jones MW,et al.Subfield-specific immediate early gene expression associated with hippocampal long-term potentiation in vivo[J].Eur J Neurosci,2001,13(5):968-976.
[16]Dong J,Yin H,Liu W,et al.Congenital iodine deficiency and hypothyroidism impair LTP and decrease C-fos and C-jun expression in rat hippocampus[J].Neurotoxicology,2005,26(3):417-426.
[17]随力,任杰.甲状腺激素在脑学习和记忆功能中的作用[J].中国药理学通报,2010,26(11):1538-1540.
[18]Gilbert ME,Sui L.Dose-dependent reductions in spatial learning and synaptic function in the dentate gyrus of adult rats following developmental thyroid hormone insufficiency[J].Brain Res,2006,1069(1):10-22.
[19]Alzoubi KH,Gerges NZ,Aleisa AM,et al.Levothyroxin restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory:Behavioral,electrophysiological,and molecular studies[J].Hippocampus,2009,19(1):66-78.
[20]刘连杰,殷洪博,王萍,等.碘缺乏甲状腺功能减退对仔鼠海马LTP的影响[J].中国公共卫生,2005,21(6):701-702.