增塑剂DEHP暴露对青春期小鼠社会行为的影响
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摘要
为探讨邻苯二甲酸二乙基己酯(di-ethylhexyl phthalate,DEHP)对青春期小鼠社会行为的影响.以旷场行为、高架十字迷宫、强迫游泳等行为模型实验检测小鼠焦虑抑郁行为,western blot实验检测雄激素受体(androgen receptor,AR)、多巴胺转运体(Dopamine transporter,DAT)、多巴胺受体(dopamine receptor 2,D2)的表达水平,激光共聚焦显微镜观测离体培养海马神经元的树突形态.研究结果表明:青春期DEHP暴露降低小鼠脑和血清雄激素水平,减少社会探究和社会交互能力,加剧焦虑抑郁状态;纹状体脑区多巴胺受体D2和雄激素受体AR水平下调;抑制神经元树突发育.总之,青春期DEHP暴露会抑制小鼠的社会行为,加剧其焦虑抑郁情绪,脑内雄激素和多巴胺递质系统活动及神经元树突形态的改变可能与此有关.
It was aimed to investigate the effects of di-ethylhexyl phthalate(DEHP) on the social behavior of adolescent mice. The behavior was detected by open field, elevated cross maze, and forced swimming task, androgen receptor(AR) and dopamine receptor 2(D2) were examined by Western blot analyses, and the morphology of hippocampal neurons in vitro was observed by using cultured hippocampal neuron in vitro. The results showed that adolescent DEHP exposure lowered androgen levels in the brain and serum, decreased social inquiry and social interaction, and exacerbated anxiety and depression. DEHP down-regulated the levels of D2 and AR in the striatum region of brain and decreased the density of dendritic spine of hippocampal neuron. Therefore, DEHP exposure would inhibit the social behavior and aggravate anxiety and depression of puberty mice, which might be associated with the change of sex hormone levels and the reduction of the levels of D2 and AR in the brain and the inhibition of neuronal dendritic development.
It was aimed to investigate the effects of di-ethylhexyl phthalate(DEHP) on the social behavior of adolescent mice. The behavior was detected by open field, elevated cross maze, and forced swimming task, androgen receptor(AR) and dopamine receptor 2(D2) were examined by Western blot analyses, and the morphology of hippocampal neurons in vitro was observed by using cultured hippocampal neuron in vitro. The results showed that adolescent DEHP exposure lowered androgen levels in the brain and serum, decreased social inquiry and social interaction, and exacerbated anxiety and depression. DEHP down-regulated the levels of D2 and AR in the striatum region of brain and decreased the density of dendritic spine of hippocampal neuron. Therefore, DEHP exposure would inhibit the social behavior and aggravate anxiety and depression of puberty mice, which might be associated with the change of sex hormone levels and the reduction of the levels of D2 and AR in the brain and the inhibition of neuronal dendritic development.
引文
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[14]BELL M R.Endocrine-disrupting actions of PCBs on brain development and social and reproductive behaviors[J].Current Opinion in Pharmacology,2014,19:134-144.
[15]LIU T,LI N,ZHU J,et al.Effects of di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-ovarian axis in adult female rats[J].Reproductive Toxicology,2014,46(7):141-147.
[16]TANG A C,NAKAZAWA M,ROMEO R D,et al.Effects of long-term estrogen replacement on social investigation and social memory in ovariectomized C57BL/6 mice[J].Hormones and Behavior,2005,47(3):350-357.
[17]ZULOAGA D G,ZULOAGA K L,HINDS L R,et al.Estrogen receptor β expression in the mouse forebrain:Age and sex differences[J].Journal of Comparative Neurology,2014,522(2):358-371.
[18]XU X,YANG Y,WANG R,et al.Perinatal exposure to di-(2-ethylhexyl) phthalate affects anxiety- and depression-like behaviors in mice[J].Chemosphere,2015,124(1):22-31.
[19]TREZZA V,BAARENDSE P J,VANDERSCHUREN L J.The pleasures of play:Pharmacological insights into social reward mechanisms[J].Trends in Pharmacological Sciences,2010,31(10):463-469.
[20]BEATTY W W,COSTELLO K B,BERRY S L.Suppression of play fighting by amphetamine:Effects of catecholamine antagonists,agonists and synthesis inhibitors[J].Pharmacology Biochemistry and Behavior,1984,20(5):747-755.
[21]ZHU X,PENG S,ZHANG S,et al.Stress-induced depressive behaviors are correlated with Par-4 and DRD2 expression in rat striatum[J].Behavioural Brain Research,2011,223(2):329-335.
[2]张婉,胡珊,许丁亮,等.孕期邻苯二甲酸二乙基己酯(DEHP)暴露对胎儿生长发育的影响[J].长江大学学报(自然科学版),2016,13(6):78-81.
[3]ANDRADE A J,GRANDE S W,TALSNESS C E,et al.A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl)-phthalate (DEHP):Non-monotonic dose-response and low dose effects on rat brain aromatase activity[J].Toxicology,2006,227(3):185-192.
[4]潘亮,于涛,刘艳华,等.胚胎期暴露DEHP对子代大鼠神经行为的影响[J].中国工业医学杂志,2012,25(2):97-99.
[5]张晶莹,宋昕恬,孟令仪.不同剂量的DEHP对子代大鼠学习记忆的影响[J].中国实用医药,2012,7(10):246-248.
[6]SETA D D,MINDER I,BELLONI V,et al.Pubertal exposure to estrogenic chemicals affects behavior in juvenile and adult male rats[J].Hormones and Behavior,2006,50(2):301-307.
[7]王冬.邻苯二甲酸二乙基己酯对小鼠学习与记忆的影响及机制研究[D].武汉:华中师范大学,2013:29-33.
[8]DAI Y,YANG Y,XU X,et al.Effects of uterine and lactational exposure to di-(2-ethylhexyl) phthalate on spatial memory and NMDA receptor of hippocampus in mice[J].Hormones and Behavior,2015,71:41-48.
[9]HUANG J H,HUANG X H,CHEN Z Y,et al.Dose conversion among diferent animals and healthy volunteers in pharmacological study[J].Chin J Clin Pharmacol Ther,2004,9:1069-1072.
[10]VANDERSCHUREN L J,NIESINK R J,VAN REE J M.The neurobiology of social play behavior in rats[J].Neuroscience and Biobehavioral Reviews,1997,21(3):309-326.
[11]NADLER J J,MOY S S,DOLD G,et al.Automated apparatus for quantitation of social approach behaviors in mice[J].Genes Brain and Behavior,2004,3(5):303-314.
[12]FUJIMOTO T,KUBO K,NISHIKAWA Y,et al.Postnatal exposure to low-dose bisphenol A influences various emotional conditions[J].Journal of Toxicological Sciences,2013,38(4):539-546.
[13]THOR D H,HOLLOWAY W R.Social play soliciting by male and female juvenile rats:Effects of neonatal and rogenization and sex of cagemates[J].Behavioral Neuroscience,1986,100(2):275-279.
[14]BELL M R.Endocrine-disrupting actions of PCBs on brain development and social and reproductive behaviors[J].Current Opinion in Pharmacology,2014,19:134-144.
[15]LIU T,LI N,ZHU J,et al.Effects of di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-ovarian axis in adult female rats[J].Reproductive Toxicology,2014,46(7):141-147.
[16]TANG A C,NAKAZAWA M,ROMEO R D,et al.Effects of long-term estrogen replacement on social investigation and social memory in ovariectomized C57BL/6 mice[J].Hormones and Behavior,2005,47(3):350-357.
[17]ZULOAGA D G,ZULOAGA K L,HINDS L R,et al.Estrogen receptor β expression in the mouse forebrain:Age and sex differences[J].Journal of Comparative Neurology,2014,522(2):358-371.
[18]XU X,YANG Y,WANG R,et al.Perinatal exposure to di-(2-ethylhexyl) phthalate affects anxiety- and depression-like behaviors in mice[J].Chemosphere,2015,124(1):22-31.
[19]TREZZA V,BAARENDSE P J,VANDERSCHUREN L J.The pleasures of play:Pharmacological insights into social reward mechanisms[J].Trends in Pharmacological Sciences,2010,31(10):463-469.
[20]BEATTY W W,COSTELLO K B,BERRY S L.Suppression of play fighting by amphetamine:Effects of catecholamine antagonists,agonists and synthesis inhibitors[J].Pharmacology Biochemistry and Behavior,1984,20(5):747-755.
[21]ZHU X,PENG S,ZHANG S,et al.Stress-induced depressive behaviors are correlated with Par-4 and DRD2 expression in rat striatum[J].Behavioural Brain Research,2011,223(2):329-335.