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慢性应激大鼠中枢5-羟色胺含量及色氨酸羟化酶-2的表达变化

Expression of TPH-2 and content of 5-HT in the brain of rats with chronic unpredictable mild stress

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【作者】 朱敏捷肖世富张盛宇房圆禹顺英董晓蔚李霞

【Author】 ZHU Min-jie;XIAO Shi-fu;ZHANG Sheng-yu;Shanghai Mental Health Center,Shanghai Jiaotong University School of Medicine;

【机构】 上海交通大学医学院附属精神卫生中心华东师范大学认知神经科学研究所

【摘要】 目的 探讨慢性不可预知轻度刺激(CUMS)大鼠模型中枢5-羟色胺(5-HT)含量、和色氨酸羟化酶-2(TPH-2)的表达变化以及抗抑郁药的影响。方法 24只大鼠被随机分成3组,每组8只,A组为对照组,不给予刺激;B组为刺激不给药组,即CUMS应激鼠;C组为刺激给药组,即CUMS应激+西酞普兰治疗组。实验为期6周,每周为大鼠称重,每3周测大鼠的糖水偏爱性,造模前后通过旷场试验评价大鼠行为,6周后对大鼠进行处死。处死后脑组织取样测定各脑区5-HT浓度及TPH-2 mRNA的表达水平。结果 经过6周干预,与A组比较,B组和C组体重明显降低(P<0.05);与A组及C组比较,B组糖水偏爱度显著降低(P<0.05),同时行为增多;B组5-HT浓度在海马中高于A组和C组,差异有统计学意义(P<0.05);在纹状体中,B组和C组5-HT浓度低于A组,差异有统计学意义(P<0.05);B组大鼠TPH2 mRNA在中缝核中表达低于A组,差异有统计学意义(P<0.05)。结论 慢性应激可能引起中枢海马5-HT浓度增高及中缝核TPH-2表达降低,抗抑郁药可能引起中枢海马5-HT浓度降低,但未能影响中枢TPH-2的表达。

【Abstract】 Objective To investigate the expression of TPH-2 and the content of 5-HT in different areas of the brain in rats with chronic unpredictable mild stress(CUMS),and explore the effects of antidepressant on expression of TPH-2 and content of 5- HT.Methods Twenty-four male SD rats were randomly assigned to control group(group A),CUMS group(group B),and CUMS + citalpram group(group C) with 8 rats in each group.The experiment lasted for 6 weeks.Body weight was measured each week,sugar preference was evaluated every 3 weeks,and behavior of rats was assessed through open field tests before model establishment and 6 weeks after model establishment.Animals were sacrificed after 6 weeks,brain tissues were obtained,and the expression of TPH-2 mRNA and the content of 5- HT in different areas of brain detected.Results After the beginning of stress experiment,the body weight of rats in group B and group C was significantly lower than that in group A(P <0.05).Rats in group B has significantly lower sugar preference than group A and group C(P < 0.05),and had higher activity.The content of 5- HT in hippocampus of rats in group B was higher than that in group A and group C,while there was significant difference between them(P< 0.05),The content of 5- HT in striatum of rats in group B and group C was lower than that in group A(P-< 0.05).The expression of TPH-2 mRNA in raphe nuclei of rats in group B was lower than that in group A(P <0.05).Conclusions Chronic stress may increase the content of 5-HT in hippocampus and decrease the expression of TPH-2 in raphe nuclei,while antidepressant may decrease the content of 5-HT in hippocampus without affecting the expression of TPH-2.

【基金】 国家自然科学基金青年项目(81101007);上海市公共卫生海外人才留学项目(WHW201215)
  • 【文献出处】 神经疾病与精神卫生 ,Journal of Neuroscience and Mental Health , 编辑部邮箱 ,2014年01期
  • 【分类号】R749.4
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