慢性应激诱导的抑郁大鼠纹状体par-4基因的表达

为研究慢性温和应激诱导的抑郁大鼠纹状体内前列腺凋亡反应蛋白(prostate apoptosis response-4, par-4)的表达, 及甲基化是否参与par-4基因表达的调控, 将10周龄大鼠随机分为实验组和对照组, 实验组接受慢性温和应激, 对照组不接受实验性处理。于大鼠13周龄时, 采用强迫游泳、糖水偏爱测验测定大鼠的抑郁水平, 以实时定量PCR检测纹状体par-4及多巴胺D2受体(Dopamine receptor D2, DRD2) mRNA表达水平, 免疫印迹法检测纹状体par-4蛋白质表达水平, 用亚硫酸盐测序法检测par-4基因启动子区甲基化水平。结果发现, 与对照组大鼠相比, 实验组大鼠漂浮时间延长, 糖水偏爱率降低, 脑纹状体par-4、DRD2 mRNA及par-4蛋白质表达水平均降低, par-4基因启动子区甲基化水平两组差异不显著。提示慢性温和应激诱导大鼠产生了抑郁样行为, 并能抑制纹状体par-4基因的表达, 而基因甲基化可能并不参与其调控机制。     

慢性应激诱导的抑郁小鼠神经肽Y的表达及抗抑郁药的作用

神经肽Y是一个多肽,广泛分布于周围和中枢神经系统,以下丘脑的浓度为高,参与机体神经内分泌、情绪、行为等的调节。 为探讨慢性应激诱导的抑郁模型小鼠脑内神经肽Y (NPY)的表达,以及抗抑郁药的作用机理,采用慢性应激与孤养方法,建立抑郁小鼠模型。用旷场行为 (Open-Field)法,观察模型组与正常对照组行为学改变方面的差异。将36 只抑郁模型小鼠随机分成盐酸氟西汀组、盐酸阿米替林组、生理盐水治疗组,并与12 只正常对照组比较。用半定量逆转录－聚合酶联反应(RT－PCR) 法、细胞酶联免疫法及蛋白免疫印迹(Western－blot) 法、免疫组织化学法,比较四组小鼠下丘脑NPY 的表达。结果表明：(1)与正常组比较,抑郁模型组小鼠活动总路程与活动次数减少（p< 0.01）,体重增速下降（p< 0.05）。（2）与正常组比较,抑郁模型组小鼠下丘脑NPY 的mRNA 表达下降（p< 0.01）;经盐酸氟西汀、盐酸阿米替林治疗后,下丘脑NPY 的mRNA 及蛋白表达增高,与生理盐水组比较差异显著（p< 0.01）。(3) 与正常组比较,生理盐水治疗组胞膜和胞质呈棕黄色染色,显示出明显的免疫组化阳性反应;经盐酸氟西汀、盐酸阿米替林治疗后,胞膜和胞质的着色与背景色接近,免疫组化呈弱阳性、阴性反应。提示抑郁模型组小鼠脑内NPY 表达水平有显著下降,使用抗抑郁药有利于提高脑内NPY 的mRNA 及蛋白表达,可能是此类药物产生抗抑郁效应的机制之一。     

Fear of Hypoglycemia and Self Reported Posttraumatic Stress in Adults with Type I Diabetes Treated by Intensive Regimens

This study investigated the prevalence of hypoglycemic fear (FH) and hypoglycemia-specific posttraumatic stress (PTS) among individuals with Type I diabetes. Over 25% of participants met diagnostic criteria for current PTSD. High percentages of participants endorsed PTS symptom clusters, suggesting that individuals may be experiencing distress without necessarily meeting diagnostic criteria. Hierarchical multiple regression analyses revealed that perceived threat of death from hypoglycemia and FH were significantly related to PTS. Number of recent hypoglycemic episodes did not predict PTS/PTSD. Depression and nonspecific anxiety did not contribute to the statistical prediction of PTSD, suggesting that symptomatology endorsed represents hypoglycemia-specific anxiety rather than global psychological distress. The hypothesis that greater PTS symptomatology would relate to poorer glycemic control was unsubstantiated. Perceived death-threat from hypoglycemia and nonspecific anxiety were the only variables that contributed to prediction of glycemic control, suggesting that PTS did not represent a significant barrier for glycemic control in this sample.