阿尔茨海默病大鼠海马热休克蛋白70表达变化的研究

目的:双侧海马注射Aβ1-42建立大鼠阿尔茨海默病(AD)模型,研究其海马热休克蛋白70(HSP70)表达的变化并探讨与AD病理进程可能存在的联系。方法:48只SD大鼠随机分为模型组与生理盐水对照组,双侧海马分别注射Aβ1-42,分别于术后1天、7天、14天、21天在Y迷宫行为学测试后处死大鼠,采用RT-PCR和Western-blot方法,观察各组大鼠海马HSP70表达的变化。结果:术后14天、21天模型组学习记忆能力较对照组和术前明显减退(P<0.05)。术后模型组大鼠海马HSP70表达逐渐减少,术后7天(mRNA:0.34±0.05;蛋白:0.29±0.03)、14天(mRNA:0.32±0.06;蛋白:0.23±0.04)与对照组比较差异有统计学意义(P<0.05),至术后21天,模型组HSP70表达减少最为明显(mRNA:0.29±0.04;蛋白:0.11±0.03)(P<0.01)。结论:大鼠海马注射Aβ1-42导致HSP70表达减少,HSP70表达减少可能参与了AD的病理发展过程。     

替普瑞酮诱导AD模型大鼠海马HSP70表达及其神经保护作用的研究

目的 研究替普瑞酮（Geranylgeranylacetone，GGA）诱导阿尔茨海默病（Alzheimer disease，AD）模型大鼠海马热休克蛋白70（heat shock protein70，HSP70）表达及其对AD大鼠的神经保护作用。方法 90只SD大鼠随机分为替普瑞酮组、模型组与生理盐水组，双侧海马注射Aβ1-42。建立阿尔茨海默病大鼠模型，替普瑞酮组给予替普瑞酮800mg·kg^-1·d^-1灌胃，余两组给予等量生理盐水灌胃；术后1d、7d、14d、21d并于Y迷宫行为学测试后处死大鼠；采用western-blot方法检测各组大鼠海马HSP70表达的变化，HE染色观察海马神经元形态学改变，TUNEL法检测海马神经元凋亡。结果术后14d、21d模型组大鼠学习记忆能力较生理盐水组明显减退（P〈0．05），替普瑞酮组较模型组明显改善（P〈0．05）；术后7d、14d、21d模型组大鼠海马HSP70表达较生理盐水组逐渐减少（P〈0．05），替普瑞酮组HSP70表达明显增加（P〈0．05）；术后21d模型组大鼠海马CA1区神经元结构紊乱，细胞减少，凋亡细胞较生理盐水组明显增加（P〈0．01），替普瑞酮组凋亡细胞较模型组显著减少（P〈0．05），细胞形态学改变减轻。结论替普瑞酮能够诱导AD模型大鼠海马HSP70表达，减少大鼠海马神经元凋亡而产生神经保护作用，改善大鼠的学习记忆能力。     

阿托伐他汀对β淀粉样蛋白1-42诱导阿尔茨海默病大鼠模型的抗炎作用

目的 探讨阿托伐他汀对β淀粉样蛋白1-42(β-amyloid 1-42,Aβ1-42)诱导阿尔茨海默病(Alzheimer's disease,AD)大鼠模型学习记忆功能及脑内炎性因子的分泌、神经细胞损伤的影响.方法 将60只Wistar大鼠(体重300～350 g)完全随机分为对照组、模型组、他汀对照组和治疗组,每组各15只.服用阿托伐他汀(每天5 mg/kg)3周为治疗组,采用侧脑室注射Aβ1-42的方法制备大鼠痴呆模型,设假手术组为对照组.水迷宫实验观测大鼠的行为学变化,免疫组织化学方法测定海马区炎性因子IL-1β、IL-6、TNF-α的表达,HE染色观察海马区形态结构的变化,透射电镜观察海马区神经元和小胶质细胞超微结构的变化.结果 模型组大鼠的学习记忆成绩下降(逃避潜伏期:对照组12.0±1.2,模型组41.3±3.4,t=18.0363,P<0.01),海马区炎性因子IL-1β、IL-6、TNF-α分泌增多(IL-1β:对照组53.5±2.4,模型组101.0±3.8,t=23.8246,P<0.01);阿托伐他汀治疗组与模型组大鼠相比较,学习和记忆成绩有所改善(逃避潜伏期:25.7±1.6,41.3±3.4,t=9.1076,P<0.01),海马区IL-1β、IL-6、TNF-α分泌减少(IL-1β:60.0±3.4,101.0±3.8,t=18.0231,P<0.01).细胞形态学观察显示,与模型组相比,阿托伐他汀治疗组模型海马区神经细胞损伤减轻,胶质细胞增生减少.结论 阿托伐他汀可以减少大鼠AD模型海马区胶质细胞炎性因子的分泌,减轻神经细胞损伤,改善其学习和记忆能力.     

拟阿尔茨海默病模型大鼠海马CA1区HSP27及IL-1表达

目的 探讨Aβ(β-淀粉样肽)诱AD大鼠模型中海马HSP27和IL-1的表达, 研究信号转导及炎性机制在AD中的作用.方法 采用立体定向下双侧海马注射Aβ1-42建立AD动物模型,通过免疫组化染色及Western blot等方法, 观测大鼠学习记忆能力、海马组织结构的病理改变及HSP27和IL-1 的表达情况.结果 HE染色显示,模型组大鼠海马神经元变性、缺失,胶质细胞浸润;免疫组化结果显示模型组大鼠海马CA1区HSP27和IL-1 免疫阳性细胞表达多见(P＜0.05);Western blot显示模型组海马组织HSP条带增宽表达强度高于对照组(P＜0.05).结论 HSP27在AD的炎症反应机制中可能具有重要作用.     

褪黑素对Alzheimer病模型大鼠认知功能和海马tau蛋白过度磷酸化的影响

目的 研究褪黑素(MT)对Alzheimer病(AD)模型大鼠认知功能和海马tau蛋白过度磷酸化的影响.方法 给大鼠海马内注射凝聚态β-淀粉样蛋白(Aβ)25-35制作AD模型;MT组大鼠从制模前7 d至制模后19 d每日腹腔注射MT,AD组大鼠制模后腹腔注射生理盐水;用Morris水迷宫试验检测大鼠的认知功能,银染法观察海马神经元形态,免疫组化法观察过度磷酸化tau蛋白的表达,并与正常对照组比较.结果 MT组大鼠Morris水迷宫试验结果明显好于AD组(均P＜0.001);海马CA1区磷酸化tau蛋白阳性细胞数(60.0±2.3)明显少于AD组(98.4±3.0)(P＜0.001),与正常对照组比较差异无统计学意义;海马CA1区神经元纤维形态较AD组规则.结论 MT可明显改善AD大鼠的认知功能,并且抑制海马tau蛋白的过度磷酸化.     

PTZ诱导孕鼠痫性发作对胎鼠海马中bax、bcl-2、capase-3表达的影响

目的探讨母鼠孕期痫性发作对胎鼠海马中bax、bcl-2、capase-3表达的影响。方法将雌性SD大鼠随机分为正常对照组(NC组)、盐水组(NS组)和癫痫组(PTZ组),采用戊四氮(pentylenetetrazol,PTZ)致痫模型,PTZ组大鼠每天给予腹腔下注射PTZ 35 mg/kg,点燃成功后将雌性SD大鼠与雄性SD大鼠合笼;发现阴栓记为孕0d,孕鼠继续孕前处理至孕20d。NS组腹腔注射相应剂量的生理盐水,NC组不做任何处理。Western Blot方法测定胎鼠海马组织中bax、bcl-2及caspase-3蛋白表达变化。结果 PTZ组胎鼠海马caspase-3蛋白(2.57±0.08)较NC组(0.53±0.13)明显升高(P<0.05);PTZ组胎鼠海马bax蛋白(3.24±0.32)较NC组(1.55±0.11)明显升高(P<0.05);PTZ组子鼠海马bcl-2表达水平(1.42±0.074)较NC组(2.45±0.07)明显降低(P<0.05)。结论孕期痫性发作使胎鼠海马促凋亡蛋白bax表达增加,抑凋亡蛋白bcl-2表达降低,凋亡执行蛋白caspase-3表达增加,推测孕期痫性发作可能使胚胎海马神经元凋亡增加。     

绿茶多酚对戊四氮致痫大鼠海马XIAP和Caspase-3表达的影响

目的 探讨绿茶多酚(Green tea polyphenols,GTPs)对癫痫大鼠海马中XIAP、caspase-3表达的影响.方法 将雄性Wistar大鼠随机分为正常对照组(NS组)、癫痫组(PTZ组)和绿茶多酚组(GTPs组).依据Racine分级标准观察各组动物行为学表现,用HE染色观察大鼠海马神经元损伤情况,Western Blot方法测定各组大鼠海马组织中XIAP及caspase-3蛋白表达变化.结果 PTZ组:大鼠海马XIAP表达水平(0.23±0.02)较NS组(0.47±0.05)明显降低(P＜0.05);caspase-3蛋白(0.63±0.12)较NS组(0.24±0.07)明显升高(P＜0.05).与PTZ组比较,GTPs组大鼠海马XIAP表达(0.53±0.10)显著升高(P＜0.05);caspase-3表达(0.30±0.09)显著降低(P＜0.05).结论 癫痫可导致海马组织中抗凋亡蛋白XIAP表达下降,凋亡执行蛋白caspase-3表达增加;而GTPs则能够上调XIAP表达,降低caspase-3的表达,推测GTPs可能通过抗凋亡途径来发挥癫痫后的神经保护作用.     

促红细胞生成素对β淀粉样蛋白诱导大鼠海马CA1区细胞凋亡的保护作用及机制

目的 探讨促红细胞生成素(Erythropoietin,EPO)对阿尔茨海默病(Alzheimer disease,AD)大鼠脑损伤的保护机制.方法 采用大鼠海马内注射B淀粉样蛋白制作AD模型.将SD大鼠随机分为假手术对照组、生理盐水对照组及EPO处理组.大鼠海马内注射Aβ1-40加造模,然后在生理盐水对照组大鼠行脑室立体定向注射生理盐水,EPO处理组则行脑室立体定向注射重组人促红细胞生成素(rHu-EPO).观察手术后24h大鼠海马CA1区抗凋亡蛋白Bcl-xl表达变化,以及术后7d海马CA1区细胞凋亡变化.结果 EPO处理组和生理盐水组海马CA1区大鼠Bcl-xl蛋白表达较假手术对照组减少,但是EPO处理组Bcl-xl蛋白表达高于生理盐水(P<0.05).生理盐水组海马CA1区凋亡细胞明显多于EPO组(P<0.05).结论 EPO可以抑制β淀粉样蛋白诱导海马CA1区细胞凋亡,与其抑制Bcl-xl蛋白表达下降有关.     

胰高血糖素样肽1(GLP-1)改善阿尔茨海默病大鼠模型的认知功能及其机制研究

目的 探讨胰高血糖素样肽1(GLP-1)改善阿尔茨海默病大鼠认知功能的机制。方法 以正常成年雄性SD大鼠为研究对象,将其随机分为正常对照组、AD模型组、AD模型+GLP-1干预组和AD模型+PPARγ抑制剂+GLP-1干预组; 其中AD模型组以侧脑室注射STZ(3 mg/kg,10 μL)制造AD模型,AD模型+GLP-1干预组在AD造模基础上每日腹腔注射利拉鲁肽(200 μg/kg,10 μL),连续给药28 d,AD模型+PPARγ抑制剂+GLP-1干预组在AD造模基础上侧脑室注射PPARγ抑制剂GW9662(2.5 nmol/g,10 μL),随后腹腔注射利拉鲁肽(200 μg/kg,10 μL)并连续给药28 d; 观察4组大鼠在Morris水迷宫中的学习和记忆能力变化; ELISA方法观察各组大鼠海马Aβ42的水平; Western blot观察各组大鼠海马PPARγ蛋白表达水平。结果 与AD模型组比较,GLP-1干预后的AD大鼠在Morris水迷宫中学习和记忆能力明显改善,海马Aβ42的水平显著降低,海马PPARγ蛋白表达水平显著升高(P<0.05); 与AD模型+GLP-1干预组比较,AD模型+PPARγ抑制剂+GLP-1干预组大鼠海马PPARγ蛋白表达水平显著降低,在Morris水迷宫中学习和记忆能力明显下降,海马Aβ42的水平显著增高(P<0.05)。结论 GLP-1可能通过激活PPARγ抑制Aβ 蓄积,从而起到改善阿尔茨海默病的认知功能作用。     

尿酸对阿尔茨海默病大鼠学习记忆能力的影响及其机制

目的 观察尿酸对阿尔茨海默病(Alzheimer disense,AD)大鼠学习记忆能力的影响,并探讨作机制.方法 Morris水迷宫实验筛选出90只大鼠,随机分为空白对照组,模型对照组.尿酸处理组(1～4组),每组15只.Aβ1-42海马注射制作AD模型,用Morris水迷宫实验观察干预前后大鼠空间学习记忆能力的变化,丙二醛(malondialdehyde,MDA)试剂盒测定海马区MDA的含量;免疫组化染色测定半胱氨酸天冬氨酸蛋白酶-3(caspase-3)的表达.结果 与空白对照组比较,模型对照组大鼠空间学习记忆能力下降(P<0.01),海马区MDA含量和caspase-3明显增高(P<0.01);与模型对照组比较,2种剂量尿酸处理组大鼠的学习记忆能力明显改善(P<0.01).海马区MDA和caspase-3的表达减少(P<0.01).结论 尿酸具有改善AD大鼠空间学习记忆作用,可能与抗氧化应激作用及抑制海马中easpase-3表达有关.     

Physical and Sexual Abuse and Neglect and Eating Disorder Symptoms

For eating-disordered patients with a history of post-traumatic stress, childhood abuse and neglect, and dissociative disorder, eating behavior symptoms may function as a rational response to unmetabolized traumatic experiences. This paper will review trauma-based theory, dissociation, abreactive, and ego-states therapy as they apply to eating disorder patients.     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

Presence and severity of anorexia and bulimia among male and female Omani and non-Omani adolescents

OBJECTIVE: The population of Oman is a heterogeneous mix of nationalities providing a natural setting for studying the cross-cultural differences in the presence and severity of eating disorders as well as an opportunity for evaluating the performance of measurement instruments for these disorders. METHOD: Disordered eating screening instruments (the Eating Attitude Test and the Bulimic Investigatory Test) were administered to Omani teenagers, non-Omani teenagers, and Omani adults. RESULTS: On the Eating Attitude Test, 33% of Omani teenagers (29.4% females and 36.4% males) and 9% of non-Omani teenagers (7.5% of males and 10.6% females) showed a propensity for anorexic-like behavior. On the Bulimic Investigatory Test, 12.3% of Omani teenagers showed a propensity for binge eating or bulimia (13.7% females and 10.9% males). Among the non-Omani teenagers, 18.4% showed a tendency toward bulimia, with females showing a slightly greater tendency than males. In contrast, barely 2% of Omani adults showed either a presence of or a severity of disorderly behavior with food. CONCLUSION: Omani teenagers scored significantly higher than other ethnic groups and Omani adults. This finding is discussed in the light of emerging evidence from many parts of the world suggesting that cultural transition, compounded by demographic constraints, plays a significant role in abnormal eating attitudes.     

Physical and Sexual Abuse and Neglect and Eating Disorder Symptoms

Abstract

For eating-disordered patients with a history of post-traumatic stress, childhood abuse and neglect, and dissociative disorder, eating behavior symptoms may function as a rational response to unmetabolized traumatic experiences. This paper will review trauma-based theory, dissociation, abreactive, and ego-states therapy as they apply to eating disorder patients.     

Micro-affirmations and Recovery for Persons with Mental Health and Alcohol and Drug Problems: User and Professional Experience-Based Practice and Knowledge

Recurrent factors contributing to a recovery process from co-occurring mental health and addiction problems mentioned by users and professionals have been analyzed as part of working alliances and helpful relationships. Still, we lack knowledge about how helpful relationships are developed in daily practice. In this article, we focus on the concrete construction of professional helpful relationships. Forty persons in recovery and fifteen professionals were interviewed. The interviews were analyzed according to thematic analysis, resulting in three themes presented as paradoxes (1) My own decision, but with the help of others; (2) The need for structures and going beyond them; and (3) Small trivial things of great importance. Micro-affirmations have a central role in creating helpful relationships by confirming the individuals involved as more than solely users or professionals. More attention and appreciation should be paid to practices involving micro-affirmations.

     

Opiate and digitalis receptor assays distinguish between neuroexcitant and inactive organochlorines and between anesthetics and convulsants

Specific binding of [3H]naloxone to rat brain tissue in vitro was inhibited by the excitant organochlorinated insecticides (OCI), by ether (E) and octanol (OCT), and by the convulsant indoklon (IND) and its anesthetic isomer, isoindoklon (ISO). In the presence of 100 mM NaCl the inhibition of naloxone binding by E, OCT and ISO was greatly potentiated, whereas that by OCI and IND was attenuated. KCl (100 mM) was equally effective as NaCl on the action of anesthetics, but the effect of the excitant drugs was, in contrast to NaCl, unaffected by KCl. Specific binding of [3H]ouabain in the absence of Na, was depressed by anesthetics and enhanced by neuroexcitants. In the presence of NaCl, which by itself inhibits ouabain binding to brain, both anesthetics and excitants enhanced ouabain binding. DDE, a non-insecticidal analog of DDT, and the dimethyl derivative of the OCI, lindane, were inactive in the receptor assays. These observations point to a unique isolated system which responds consistently to anesthetic agents as a class and, in a different way, to neuroexcitant compounds.