摘要
目的探讨慢性应激状态下,以及持续给予盐酸氟西汀后,大鼠海马及前额叶部位环磷酸腺苷反应元件结合蛋白(cAMP-response element binding protein,CREB)水平和磷酸化CREB(p-CREB)表达的变化。方法成年雄性Sprague-Dawley(SD)大鼠50只随机分为三组:应激组26只,药物组12只,对照组12只。应激组与药物组大鼠均经过8周慢性应激刺激,药物组在第1周开始给予盐酸氟西汀(10mg/g,I.P.),直到8周末。8周后行糖水偏好实验和旷场实验,根据8周末糖水偏爱率将应激组大鼠分为应激敏感组和应激适应组。应激结束后将四组大鼠断头处死,采用蛋白免疫印记技术检测大鼠海马、额叶部位CREB和p-CREB水平。结果 8周末应激敏感组糖水偏爱率低于应激适应组、药物组及对照组(均P<0.05);应激敏感组的跨格次数、中心格时间和直立次数低于药物组和对照组(均P<0.05),与应激适应组无统计学差异(均P>0.05)。应激敏感组海马及前额叶中p-CREB水平明显低于应激适应组、药物组及对照组(均P<0.05);四组大鼠海马部位、前额叶CREB表达水平无明显差异。结论海马和额叶部位CREB磷酸化水平可能与应激导致的情绪障碍发生机制相关。
Objective To better understand the role of CREB signaling pathway in chronic mild stress （CMS）, we investigated the alteration of CREB and p-CREB in CMS rats with and without fluoxetine hydroehloride. Methods Fifty adult male Sprague-Dawley rats were randomly divided into three groups： CMS group （26）, fluoxtine group （12） and con-trol group （12）. The rats in CMS group and fluoxtine group received 8 weeks of chronic mild stress. Rats in fluoxtine group were administered daily injections of fluoxetine lOmg/kg I.P. Sucrose preference tests and open-field test were car- ried out after the 8th week. Based on endpoint sucrose-intake, animals were further divided into 4 groups： CMS sensitive group, CMS resilient group, fluoxtine group and control group. Western blot was used to detect the expression levels of CREB and p-CREB in the hippoeampus and prefrontal cortex. Results The sucrose consumption was significantly de- creased in CMS resilience group compared to sensitive group, control group and fluoxetine-intervention group （all P〈0.05）. Similarly, the numbers in total arm entries, percentage of entries into open arms and time spent in open arms was significantly lower in CMS resilience group compared to control group（all P〈0.05）, but not different compared to CMS sensitive group（all P〈0.05）. The p-CREB in the hippocampus was significantly lower in CMS sensitive rat compared to CMS resilience group, control group and fluoxetine-intervention group（all P〈0.05）, but CREB was not dfferent among the four groups（all P〈0.05）. Conclusions The elevated phosphorylation of CREB in the hippocampus and prefrontal cortex of resilience CMS rats may contribute to the mood alteration induced by stress.
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
2014年第1期26-30,共5页
Chinese Journal of Nervous and Mental Diseases
基金
上海交通大学科学基金(编号:11XJ21006)
上海市自然科学基金(编号:09ZR1427200)
上海市卫生局公共卫生海外人才项目(编号:GWHW201208)
国家高技术研究发展计划"863"计划(编号:2006AA02Z430)
国家自然科学基金重大计划项目(编号:91232719)
国家临床重点专科-上海市精神卫生中心(编号:卫生部医政司2011-873)
