苯并[a]芘亚急性染毒后小鼠焦虑样行为及海马神经元的变化
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摘要
[目的]观察苯并[a]芘亚急性染毒后小鼠神经行为及海马CA1区神经元树突、树突棘密度的变化。[方法]48只C57BL/6小鼠随机分为对照组和低、中、高剂量苯并[a]芘染毒共4组,经腹腔注射分别给予植物油溶剂和苯并[a]芘0.8、2.0、5.0mg/kg,隔天一次,连续4周。通过糖水偏爱实验、旷场实验和高架十字迷宫实验观察苯并[a]芘亚急性染毒后小鼠神经行为学改变;采用高尔基染色观察海马CA1区内神经元树突、树突棘密度的变化。[结果]在糖水偏爱实验中,各组小鼠糖水偏好百分比[(93.71±0.99)%、(89.43±4.10)%、(89.72±1.23)%、(84.04±5.88)%]无差异(P>0.05)。在旷场实验中:高剂量组小鼠在中心区滞留时间[(50.34±12.74)s]短于对照组[(73.94±29.30)s](P<0.05);中、高剂量组小鼠中心区进入次数(15.88±8.84、13.25±7.92)少于对照组(28.00±13.33),周边区运动距离[(9688.23±1382.15)、(9926.83±1477.06)mm]较对照组[(7655.69±2392.45)mm]长(均P<0.05)。在高架十字迷宫实验中,中、高剂量组小鼠开臂进入次数(5.88±1.96、5.63±2.97)、开臂滞留时间百分比[(18.38±5.25)%、(20.90±2.27)%]均小于对照组[11.63±7.25、(39.80±8.37)%](均P<0.05)。高尔基染色结果显示高剂量组小鼠海马CA1区神经元树突总长度[(1295.88±238.26)μm]、树突分支数(16.50±1.38)及树突棘密度(每10μm中的个数)(3.20±0.79)均低于对照组[(1732.81±239.69)μm、22.17±2.56、5.90±1.20]。[结论]苯并[a]芘亚急性暴露可诱发小鼠焦虑样行为,这可能与海马CA1区神经元树突及树突棘可塑性改变相关。
[Objective] To investigate the changes of neurobehavioral performance as well as neuronal dendrites and dendritic spine density in hippocampal CA1 region of mice with subacute benzo[a]pyrene exposure(Ba P). [Methods] Forty-eight C57 BL/6 mice were randomly divided into four groups receiving either olive oil(control group) or Ba P at 0.8, 2.0, and 5.0 mg/kg(low, medium, and high dose groups) every other day for four weeks. The neurobehavioral changes of mice were observed by sucrose preference test, open field test, and elevated plus maze test. The before-and-after-treatment changes of neuronal dendrites and dendritic spine density in hippocampal CA1 region were observed by Golgi staining.[Results] In the sucrose preference test,there was no significant difference in the percentage of sucrose preference among the four groups [(93.71±0.99)%,(89.43±4.10)%,(89.72±1.23)%, and(84.04±5.88)%, respectively](P > 0.05). In the open field test,compared with the control group [residence time,(73.94±29.30) s; frequency of entering central area, 28.00±13.33; distance in surrounding area,(7 655.69±2 392.45) mm], the mice in the high dose group had shorter residence time in central area [(50.34±12.74) s], and the mice in the medium dose group and the high dose group showed a less frequency of entering central area(15.88±8.84 and 13.25±7.92) and a longer distance in surrounding area [(9 688.23±1 382.15) mm and(9 926.83±1 477.06) mm](Ps < 0.05). In the elevated plus maze test, the frequency of entry into the open arms(5.88±1.96 and 5.63±2.97) and the percentage of time spent in open arms [(18.38±5.25)% and(20.90±2.27)%] of mice in the medium and high dose groups were smaller than those in the control group [11.63±7.25,(39.80±8.37)%](P < 0.05). Golgi staining results showed that the total dendritic length [(1 295.88±238.26) μm], number of dendritic branches(16.50±1.38), and dendrite spine density per 10 μm(3.20±0.79) in the hippocampal CA1 neurons of the high dose group were lower than those in the control group [(1 732.81±239.69) μm, 22.17±2.56, and 5.90±1.20, respectively].[Conclusion] Subacute Ba P exposure could induce anxiety-like behavior in mice, which may be related to the change of plasticity of neuron dendrites and dendritic spines in hippocampal CA1 region.
[Objective] To investigate the changes of neurobehavioral performance as well as neuronal dendrites and dendritic spine density in hippocampal CA1 region of mice with subacute benzo[a]pyrene exposure(Ba P). [Methods] Forty-eight C57 BL/6 mice were randomly divided into four groups receiving either olive oil(control group) or Ba P at 0.8, 2.0, and 5.0 mg/kg(low, medium, and high dose groups) every other day for four weeks. The neurobehavioral changes of mice were observed by sucrose preference test, open field test, and elevated plus maze test. The before-and-after-treatment changes of neuronal dendrites and dendritic spine density in hippocampal CA1 region were observed by Golgi staining.[Results] In the sucrose preference test,there was no significant difference in the percentage of sucrose preference among the four groups [(93.71±0.99)%,(89.43±4.10)%,(89.72±1.23)%, and(84.04±5.88)%, respectively](P > 0.05). In the open field test,compared with the control group [residence time,(73.94±29.30) s; frequency of entering central area, 28.00±13.33; distance in surrounding area,(7 655.69±2 392.45) mm], the mice in the high dose group had shorter residence time in central area [(50.34±12.74) s], and the mice in the medium dose group and the high dose group showed a less frequency of entering central area(15.88±8.84 and 13.25±7.92) and a longer distance in surrounding area [(9 688.23±1 382.15) mm and(9 926.83±1 477.06) mm](Ps < 0.05). In the elevated plus maze test, the frequency of entry into the open arms(5.88±1.96 and 5.63±2.97) and the percentage of time spent in open arms [(18.38±5.25)% and(20.90±2.27)%] of mice in the medium and high dose groups were smaller than those in the control group [11.63±7.25,(39.80±8.37)%](P < 0.05). Golgi staining results showed that the total dendritic length [(1 295.88±238.26) μm], number of dendritic branches(16.50±1.38), and dendrite spine density per 10 μm(3.20±0.79) in the hippocampal CA1 neurons of the high dose group were lower than those in the control group [(1 732.81±239.69) μm, 22.17±2.56, and 5.90±1.20, respectively].[Conclusion] Subacute Ba P exposure could induce anxiety-like behavior in mice, which may be related to the change of plasticity of neuron dendrites and dendritic spines in hippocampal CA1 region.
引文
[1]杨凯,秦启忠,涂白杰.苯并[a]芘与铅对小鼠学习记忆能力影响协同效应[J].中国公共卫生,2016,32(1):85-88.
[2]BOUAYED J,DESOR F,SOULIMANI R.Subacute oral exposure to benzo[a]pyrene(B[a]P)increases aggressiveness and affects consummatory aspects of sexual behaviour in male mice[J].J Hazard Mater,2009,169(1/2/3):581-585.
[3]李卫星,张红明,胡志鹏,等.焦炉工人神经行为改变及其影响因素研究[J].环境与职业医学,2011,28(4):205-209,214.
[4]CHEN C,TANG Y,JIANG X,et al.Early postnatal Benzo(a)pyrene exposure in sprague-dawley rats causes persistent neurobehavioral impairments that emerge postnatally and continue into adolescence and adulthood[J].Toxicol Sci,2012,125(1):248-261.
[5]LANG P J,DAVIS M.Emotion,motivation,and the brain:reflex foundations in animal and human research[J].Prog Brain Res,2006,156:3-29.
[6]GOBINATH A R,MAHMOUD R,GALEA L A.Influence of sex and stress exposure across the lifespan on endophenotypes of depression:focus on behavior,glucocorticoids,and hippocampus[J].Front Neurosci,2015,8:420.
[7]STOCKMEIER C A,MAHAJAN G J,KONICK L C,et al.Cellular changes in the postmortem hippocampus in major depression[J].Biol Psychiatry,2004,56(9):640-650.
[8]MOIR D,VIAU A,CHU I,et al.Pharmacokinetics of benzo[a]pyrene in the rat[J].J Toxicol Environ Health Part A,1998,53(7):507-530.
[9]JEDRYCHOWSKI W A,PERERA F P,CAMANN D,et al.Prenatal exposure to polycyclic aromatic hydrocarbons and cognitive dysfunction in children[J].Environ Sci Pollut Res,2015,22(5):3631-3639.
[10]聂继盛,张红梅,孙建娅,等.焦炉作业工人神经行为功能改变的特征分析[J].中华预防医学杂志,2008,42(1):25-29.
[11]NIU Q,ZHANG H,LI X,et al.Benzo[a]pyrene-induced neurobehavioral function and neurotransmitter alterations in coke oven workers[J].Occup Environ Med,2010,67(7):444-448.
[12]GROVA N,SCHROEDER H,FARINELLE S,et al.Subacute administration of benzo[a]pyrene(B[a]P)reduces anxiety-related behaviour in adult mice and modulates regional expression of N-methyl-D-aspartate(NMDA)receptors genes in relevant brain regions[J].Chemosphere,2008,73(S1):S295-S302.
[13]何承勇,罗海兰,骆冰,等.苯并(a)芘哺乳期暴露导致母-仔代小鼠焦虑行为的研究[C]//中国毒理学会生化与分子毒理专业委员会学术会议暨环境内分泌干扰物的毒理学研究新技术新方法研讨会论文集.深圳:中国毒理学会生化与分子毒理专业委员会,2014:234-235.
[14]ZHANG W,TIAN F,ZHENG J,et al.Chronic administration of Benzo(a)pyrene induces memory impairment and anxietylike behavior and increases of NR2B DNA methylation[J].PLo S One,2016,11(2):e0149574.
[15]FU X,ZUNICH S M,O'CONNOR J C,et al.Central administration of lipopolysaccharide induces depressivelike behavior in vivo and activates brain indoleamine 2,3dioxygenase in murine organotypic hippocampal slice cultures[J].J Neuroinflammation,2010,7:43.
[16]袁璐,李晋熙,罗跃嘉.脂多糖连续注射诱发小鼠抑郁行为及认知改变[J].成都医学院学报,2017,12(5):536-540,545.
[17]陆浩慧,樊泽,王旭,等.小胶质细胞M1型极化诱发小鼠焦虑样行为及其对前额叶神经元树突棘密度的影响[J].神经解剖学杂志,2017,33(4):409-415.
[2]BOUAYED J,DESOR F,SOULIMANI R.Subacute oral exposure to benzo[a]pyrene(B[a]P)increases aggressiveness and affects consummatory aspects of sexual behaviour in male mice[J].J Hazard Mater,2009,169(1/2/3):581-585.
[3]李卫星,张红明,胡志鹏,等.焦炉工人神经行为改变及其影响因素研究[J].环境与职业医学,2011,28(4):205-209,214.
[4]CHEN C,TANG Y,JIANG X,et al.Early postnatal Benzo(a)pyrene exposure in sprague-dawley rats causes persistent neurobehavioral impairments that emerge postnatally and continue into adolescence and adulthood[J].Toxicol Sci,2012,125(1):248-261.
[5]LANG P J,DAVIS M.Emotion,motivation,and the brain:reflex foundations in animal and human research[J].Prog Brain Res,2006,156:3-29.
[6]GOBINATH A R,MAHMOUD R,GALEA L A.Influence of sex and stress exposure across the lifespan on endophenotypes of depression:focus on behavior,glucocorticoids,and hippocampus[J].Front Neurosci,2015,8:420.
[7]STOCKMEIER C A,MAHAJAN G J,KONICK L C,et al.Cellular changes in the postmortem hippocampus in major depression[J].Biol Psychiatry,2004,56(9):640-650.
[8]MOIR D,VIAU A,CHU I,et al.Pharmacokinetics of benzo[a]pyrene in the rat[J].J Toxicol Environ Health Part A,1998,53(7):507-530.
[9]JEDRYCHOWSKI W A,PERERA F P,CAMANN D,et al.Prenatal exposure to polycyclic aromatic hydrocarbons and cognitive dysfunction in children[J].Environ Sci Pollut Res,2015,22(5):3631-3639.
[10]聂继盛,张红梅,孙建娅,等.焦炉作业工人神经行为功能改变的特征分析[J].中华预防医学杂志,2008,42(1):25-29.
[11]NIU Q,ZHANG H,LI X,et al.Benzo[a]pyrene-induced neurobehavioral function and neurotransmitter alterations in coke oven workers[J].Occup Environ Med,2010,67(7):444-448.
[12]GROVA N,SCHROEDER H,FARINELLE S,et al.Subacute administration of benzo[a]pyrene(B[a]P)reduces anxiety-related behaviour in adult mice and modulates regional expression of N-methyl-D-aspartate(NMDA)receptors genes in relevant brain regions[J].Chemosphere,2008,73(S1):S295-S302.
[13]何承勇,罗海兰,骆冰,等.苯并(a)芘哺乳期暴露导致母-仔代小鼠焦虑行为的研究[C]//中国毒理学会生化与分子毒理专业委员会学术会议暨环境内分泌干扰物的毒理学研究新技术新方法研讨会论文集.深圳:中国毒理学会生化与分子毒理专业委员会,2014:234-235.
[14]ZHANG W,TIAN F,ZHENG J,et al.Chronic administration of Benzo(a)pyrene induces memory impairment and anxietylike behavior and increases of NR2B DNA methylation[J].PLo S One,2016,11(2):e0149574.
[15]FU X,ZUNICH S M,O'CONNOR J C,et al.Central administration of lipopolysaccharide induces depressivelike behavior in vivo and activates brain indoleamine 2,3dioxygenase in murine organotypic hippocampal slice cultures[J].J Neuroinflammation,2010,7:43.
[16]袁璐,李晋熙,罗跃嘉.脂多糖连续注射诱发小鼠抑郁行为及认知改变[J].成都医学院学报,2017,12(5):536-540,545.
[17]陆浩慧,樊泽,王旭,等.小胶质细胞M1型极化诱发小鼠焦虑样行为及其对前额叶神经元树突棘密度的影响[J].神经解剖学杂志,2017,33(4):409-415.