慢性应激对大鼠海马CA3区锥体细胞顶树突及血清皮质酮浓度的影响

目的探讨慢性应激对大鼠海马CA3区锥体细胞结构和血清皮质酮浓度的影响。方法将20只雄性Sprague-Dawley大鼠按体质量随机分为应激组和对照组,每组10只。采用高尔基染色法及酶联免疫分析方法,观察慢性强迫游泳应激对大鼠海马CA3区锥体细胞顶树突和血清皮质酮浓度的影响。结果应激组大鼠海马CA3区锥体细胞顶树突的总长度[(112±10)μm]短于对照组[(168±34)μm],差异有统计学意义(P<0.01);一级树突直径[(9.0±1.1)μm]大于对照组[(5.7±0.9)μm],差异有统计学意义(P<0.01);血清皮质酮浓度[(13±14)μg/L]低于对照组[(30±16)μg/L],差异有统计学意义(P<0.05)。结论慢性强迫游泳可引起大鼠海马CA3区锥体细胞顶树突及血清皮质酮浓度的改变。     

间歇性缺氧对大鼠认知功能和海马CA1区超微结构的影响

目的观察间歇性缺氧对大鼠认知功能及海马CA1区神经元超微结构的影响。方法SD雄性大鼠16只,随机分为正常组(UC,n=8)和间歇性缺氧组(IH,n=8)。UC组正常饲养,IH组每日间歇缺氧7 h建立间歇性缺氧大鼠模型,通过Morris水迷宫测试检测其学习和记忆能力,并于灌注固定后应用透射电镜观察海马CA1区超微结构。结果(1)Morris水迷宫学习成绩(定位航行实验):第5 d训练结束时IH组大鼠逃避潜伏期明显长于UC组,两组之间差异有统计学意义(P<0.05)。(2)Morris水迷宫记忆成绩:IH组穿越平台次数[(1.38±0.92)次]较UC组减少[(3.75±1.04)次](P<0.01);IH组跨越目标象限时间占整个游泳时间的百分率[(20.52±3.41)%]也较UC组减少[(39.89±5.63)%](P<0.01)。(3)电镜下可见IH组神经元细胞质的电子密度增加,核染色质浓缩并聚集核膜附近,粗面内质网排列紊乱或扩张并出现脱颗粒现象,线粒体主要表现为肿胀、空泡变性及嵴消失,突触结构分界不清,突触小泡稀疏。UC组无明显病变。结论IH可致大鼠学习记忆障碍和海马神经元超微结构改变,IH所引起的大鼠学习记忆障碍与海马神经元超微结构的改变密切相关。     

纳洛酮与舒必利对大鼠脑震荡后空间学习记忆及海马CA3区锥体细胞影响的对照研究

目的 研究比较纳洛酮和舒必利对大鼠脑震荡后空间学习记忆能力及海马CA3区锥体细胞影响的异同,并对可能发生的机制进行探讨.方法 用金属单摆打击装置制作SD大鼠脑震荡模型,将32只大鼠随机分为4组:假打击组(6只)、脑震荡组(8只)、脑震荡+纳洛酮治疗组(以下简称纳洛酮治疗组,9只)、脑震荡+舒必利治疗组(以下简称舒必利治疗组,9只).用Morris水迷宫训练方法 ,评价动物的空间学习记忆能力;用Nissl染色对海马CA3区锥体细胞计数;用激光共聚焦显微镜和钙荧光探针flou-3/AM技术,观察海马CA3区锥体细胞内钙离子荧光量值.结果 (1)行为学:打击后第8～13天脑震荡组隐匿平台逃避潜伏期长于假打击组、纳洛酮治疗组、舒必利治疗组(P＜0.01);穿越原平台位置的次数[(2.0±0.8)次/min]少于假打击组[(5.1±0.6)7欠/min]、纳洛酮治疗组[(4.8±1.0)次/min]、舒必利治疗组[(4.6±1.0)次/min],均P＜0.01.(2)海马CA3区锥体细胞计数:假打击组[(62.7±3.4)个]高于脑震荡组[(49.8±1.7)个]、纳洛酮治疗组[(57.3±1.5)个]和舒必利治疗组[(54.8±1.7)个],均P＜0.01;而纳洛酮和舒必利治疗组高于脑震荡组(P＜0.01);纳洛酮治疗组又高于舒必利治疗组(P＜0.01).(3)海马CA3区锥体细胞内游离钙荧光量:脑震荡组[(3.0±0.6)×106]高于假打击组[(1.0±0.3)×106]、纳洛酮治疗组[(0.9±0.4)×106]和舒必利治疗组[(1.1±0.3)×106],均P＜0.01.结论 大鼠脑震荡后学习记忆缺失与海马CA3区锥体细胞数减少有关;纳洛酮和舒必利对这种损害均有保护作用.     

APP17肽对APP转基因小鼠学习记忆能力和海马神经细胞凋亡的影响

目的观察APP(-βamyloid precursop protein,APP)17肽(APP695中319-335肽段)对APP转基因小鼠(APP695V717I)学习、记忆能力及海马神经细胞凋亡的影响。方法3月龄的APP695转基因小鼠随机分为模型组和APP17肽治疗组,正常对照组采用月龄和性别与之相匹配的C57BL/6J小鼠。APP17肽治疗组给予皮下注射APP17肽,每只每次0.34μg,每周3次;模型组和正常对照组给予等体积NS。应用水迷宫试验观察小鼠学习、记忆功能的变化,以流式细胞技术分析海马神经细胞凋亡率和线粒体膜电位的变化。结果(1)水迷宫试验结果显示,模型组小鼠存在明显学习和记忆功能障碍,其第3、4、5天游完全程的时间[(93.22±16.35)、(86.73±20.26)、(77.13±29.35)s]和错误反应次数[(6.63±2.16)、(5.81±2.13)、(5.33±1.41)次]均较正常对照组[分别为(70.89±20.19)、(61.25±21.88)、(54.63±16.92)s和(5.01±1.93)、(2.97±0.96)、(2.31±1.01)次]增多(P<0.05);APP17肽治疗组小鼠的行为学障碍明显轻于模型组(P<0.05),其上述水迷宫检测结果与正常对照组比较差异无统计学意义。(2)与正常对照组小鼠海马神经细胞凋亡发生率[(3.13±1.19)%]和线粒体膜电位[(176.39±13.88)mV]比较,模型组凋亡发生率[(8.06±2.31)%]显著增加(P<0.01)而线粒体膜电位[(97.51±15.73)mV]明显降低(P<0.01);APP17肽治疗组检测结果与正常对照组接近,海马神经细胞凋亡发生率[(4.38±1.26)%]低于模型组(P<0.01),线粒体膜电位[(168.35±19.29)mV]高于模型组(P<0.01)。结论APP695转基因小鼠存在学习和记忆功能障碍,且其海马神经细胞凋亡率增加,线粒体膜电位降低;APP17肽能够明显改善该转基因小鼠的学习和记忆能力,其作用机制可能是通过稳定线粒体膜电位及抑制凋亡发生而实现。     

吗啡戒断性焦虑大鼠海马突触界面结构及突触素表达变化

目的 探讨吗啡依赖戒断焦虑行为与海马CA1、CA3区突触界面结构和突触素表达变化之间的相关性.方法 剂量递增法建立大鼠吗啡依赖模型,高架十字迷宫检测焦虑行为,透射电镜技术结合图像分析系统、免疫组织化学比较对照组、模型组和治疗组(各6只)大鼠海马CA1、CA3区突触界面结构和突触素(P38)的表达.结果 (1)行为学:模型组开放臂的次数和时间均少于对照组和治疗组[最小有意义差异t检验(下同),P＜0.01或P＜0.05).(2)突触界面结构:模型组CA1区突触后致密物厚度[(10.7±0.9)nm]、突触活性区长度[(45±4)am]、突触间隙宽度[(3.80±0.30)nm]和突触界面曲率(1.37±0.12)均高于对照组和治疗组(P＜0.01或P＜0.05);模型组CA3区突触后致密物厚度[(12.7±1.1)nm]、突触活性区长度[(53±8)nm]、突触间隙宽度[(3.81 ±0.59)nm]、突触界面曲率(1.39±0.30)亦均高于对照组和治疗组(P＜0.01或P＜0.05).(3)突触素表达:模型组CA1、CA3区突触素吸光度(A)值分别为(0.42±0.06)和(0.43±0.05),显著高于对照组(0.2±0.02,0.25±0.03)和治疗组(0.27±0.04,0.26±0.03).结论吗啡戒断焦虑行为与海马CA1、CA3区突触形态结构可塑性及突触素表达水平有一定的相关性.     

低频脉冲磁场对脑缺血再灌注损伤大鼠神经元保护作用的研究

目的研究低频脉冲磁场对脑缺血再灌注损伤大鼠海马神经元的保护作用。方法将24只SD大鼠随机分成磁辐射组和对照组(每组12只),应用改良的Pulsineli法制作大鼠全脑缺血再灌注模型;将磁辐射组大鼠头部置于低频脉冲磁场(20mT、10Hz)辐射45min,每天1次,连续4d。进行脑电图监测,用Nissl染色及免疫组化方法检测海马神经元数及caspase-3蛋白阳性细胞数。结果磁辐射组脑电图振幅[(10.27±1.12)μV]和频率[(10.06±1.02)Hz]较对照组[(8.95±1.04)μV、(8.62±0.94)Hz]显著增加(均P<0.05);磁辐射组海马神经元数[(29.02±1.32)个/高倍镜视野]较对照组[(21.25±1.06)个/高倍镜视野]增多,磁辐射组caspase-3蛋白阳性细胞数[(21.33±1.32)个/高倍镜视野]较对照组[(28.34±1.10)个/高倍镜视野]减少,两组相比差异具有统计学意义(均P<0.05)。结论低频脉冲磁场可以减轻脑缺血再灌注后海马神经元的损伤及凋亡,对脑缺血再灌注损伤有保护作用。     

针刺结合运动训练干预脑梗死大鼠海马CA3区微管相关蛋白及突触素表达及学习记忆功能变化

实验观察针刺百会(GV20)、曲鬓(GB 7)和前顶穴(GV21)联合运动训练干预和件下大脑中动脉闭塞大鼠模型大鼠海马CA3区微管相关蛋白2和突触素蛋白的表达,并和单独运动训练干预的大鼠对比。Y型迷宫实验和免疫组织化学染色显示,建模后5周,针刺联合运动训练组穿越Y型迷宫错误次数均少于模型组和运动训练组,针刺联合运动训练组的微管相关蛋白2和突触素表达明显增高,各组海马CA3区的微管相关蛋白2,突触素的表达和穿越Y型迷宫错误次数均呈明显的负相关性。说明针刺联合运动训练可以改善脑梗死大鼠学习和记忆功能,其机制与海马CA3区的树突及突触可塑性有关。     

慢性强迫游泳应激对大鼠情绪和脑细胞外信号调节激酶磷酸化水平的影响

目的探讨慢性强迫游泳应激对大鼠情绪和脑细胞外信号调节激酶磷酸化(P-ERK1/2)水平的影响。方法将30只SD雄性大鼠随机分为游泳应激组、装置对照组和空白对照组,每组10只。游泳应激组每天接受5min的游泳应激,装置对照组每天接受5min的新异场景应激,均连续14 d,空白对照组不进行任何干预,然后观察大鼠行为(体质量增长量、旷场测验和糖精水溶液偏好测验)。采用免疫印迹法测定大鼠海马和前额叶皮质的P-ERK1/2。结果(1)游泳应激组在应激7d和应激14d的体质量增长[分别为(75±22)g和(70±24)g]均低于空白对照组[分别为(101±35)g和(115+47)g],均P＜0.05。(2)装置对照组的粪便排泄量[(1.4±1.9)粒]多于空白对照组[(0.4±1.0)粒]和游泳应激组[(0.1±0.3)粒],均P＜0.05；而游泳应激组的水平活动距离[(2077±1245)cm]少于空白对照组[(2990±1038)cm]和装置对照组[(3110±1462)cm],均P＜0.05。(3)游泳应激组的糖精水溶液摄入量[(11±6)g]和糖精水溶液摄入量占总液体摄入量的比例[(37±16)％]均低于空白对照组[分别为(15±4)g和(47±15)％],均P＜0.05。(4)游泳应激组在海马[(46±95)％]和前额叶皮质[(65±24)％]的P-ERK2水平均低于空白对照组[分别为(76±30)%和(99±42)%],均P＜0．05。结论慢性强迫游泳应激能诱发大鼠的抑郁情绪,降低P-ERK2在海马和前额叶皮质的水平。     

慢性应激对大鼠海马CA3区锥体细胞形态结构的效应

目的　探讨慢性应激对大鼠海马CA3区锥体细胞形态结构的效应。方法　将 2 6只雄性Sprague Dawley大鼠随机分为对照组和应激组 ,每组 13只。采用尼氏 (Nissl)染色法、高尔基 (Golgi)镀染法和透射电镜技术 ,观察慢性强迫游泳应激对大鼠海马CA3区锥体细胞形态结构的效应。结果应激组大鼠海马CA3区锥体细胞数 (35 1± 3 9)较对照组 (38 7± 3 5 )明显减少 (P <0 0 5 ) ;顶树突的总长度为 (15 5 7± 33 3) μm ,较对照组 (195 6± 34 6 ) μm明显缩短 (P <0 0 5 )。应激组大鼠海马CA3区锥体细胞出现超微结构的改变 ,包括细胞固缩、体积缩小、核膜皱缩、线粒体变性和粗面内质网模糊不清。结论　慢性应激可引起海马CA3区锥体细胞形态和微细结构的改变及细胞丧失。     

血管性痴呆大鼠海马突触素、发动蛋白Ⅰ的mRNA及蛋白表达变化

目的探讨血管性痴呆(VaD)大鼠海马突触素、发动蛋白Ⅰ的mRNA及蛋白表达变化。方法利用改良四血管法制备血管性痴呆大鼠模型。通过Morris水迷宫观察大鼠空间探索及学习记忆情况,采用Real-time及Western-blot法分别检测大鼠海马突触素、发动蛋白Ⅰ的mRNA与蛋白水平,并与假手术组进行比较。结果 VaD组大鼠各时间点平均逃避潜伏期及第1次穿越平台所用时间均显著长于假手术组(均P0.01),平台穿越次数明显减少(P0.05)。VaD组海马突触素及发动蛋白Ⅰ蛋白表达及mRNA表达显著低于假手术组(P0.05~0.01)。结论脑缺血引起大鼠海马组织突触素、发动蛋白Ⅰ表达降低,可能与VaD发病中学习记忆能力减退有关。     

沙盘游戏疗法在地中海贫血患儿心理干预中的应用

本文目的是对沙盘游戏疗法在地中海贫血患儿心理干预中的应用进行综述,以期为地中海贫血患儿的心理康复提供参考。地中海贫血是以珠蛋白生成障碍为主要特征的遗传性疾病,由于长期输血治疗,患儿存在较多的心理和行为问题。沙盘游戏疗法作为一种有效、实用的儿童心理治疗方法,对提高地中海贫血患儿的康复效果、改善生存质量有重要的临床意义。     

癫痫共病抑郁的机制及临床诊疗

本文目的是探讨癫痫共病抑郁的可能机制及临床诊疗。癫痫是一种常见的、慢性的、致残性的神经疾病,癫痫患者生活质量下降,存在明显的负性情绪,常伴发各种精神疾病。癫痫与抑郁具有共同的神经生物学基础,可能存在共同的发病机制。本文从癫痫共病抑郁的发病机制、临床诊断及治疗方面予以总结归纳。     

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.     

Cultural Identity and Experiences of Prejudice and Discrimination of Afghan and Iranian Immigrant Youth

In culturally diverse and immigrant receiving societies, immigrant youth can be subject to prejudice and discrimination. Such experiences can impact on immigrant youth’s cultural identity and influence their psychosocial outcomes. This paper presents findings of a study that examined cultural identity and experiences of prejudice and discrimination among Afghan (N = 9) and Iranian (N = 17) immigrant youth in Canada. The study had a prospective, comparative, longitudinal qualitative design. Data was gathered through focus groups, interviews, journals and field logs. Four main themes emerged on participants’ experiences of prejudice and discrimination: (a) societal factors influencing prejudice; (b) personal experiences of discrimination; (c) fear of disclosure and silenced cultural identity; and (d) resiliency and strength of cultural identity. Drawing from Rosenberg’s (Conceiving the self, Basic Books, New York, 1979) self-concept framework and Romero and Roberts (J. Adolesc., 21:641–656, 1998) distinction between prejudice and discrimination, results indicated that youth’s extant and presenting cultural identity were affected. Inclusive policies and practices are needed to promote youth integration in multicultural and immigrant receiving settings.

发作性睡病与异态睡眠的诊治

本文目的是探讨发作性睡病与异态睡眠的诊断与治疗.发作性睡病被漏诊和误诊的几率较高,危害较大,共患异态睡眠比例高.文章从发作性睡病临床特征、REM睡眠的作用、发作性睡病与异态睡眠(睡眠瘫痪、睡眠幻觉、快眼动睡眠期行为障碍)共病特征及治疗这四个方面进行了讨论.     

Effects of Agonists and Antagonists of Cholecystokinin on Contractile and Myoelectric Activity of Isolated Muscle of Colon and Ileum in the Dog and Guinea Pig

This study evaluates the effects of agonists and antagonists of cholecystokinin (CCK) on contractile and myoelectrical activity in isolated longitudinal muscle strips from colon or ileum of guinea pigs or beagle dogs. Caerulein and CCK-8 caused a dose-dependent increase of contractile and myoelectrical spike activity in both species with maximal effects seen between 10⁻⁸ and 3 × 10⁻⁸ M. The dose responses were identical for both CCK agonists and species. The dose-related effects of CCK compounds on colonic muscle were slightly shifted to the right when compared to ileum in both species. All antagonists, the proglumide-derivatives CR1409, CR1392, and CR1505, as well as the nonpeptide substances asperlicin and L-364,718, caused a parallel rightward shift of CCK's dose-dependent motor activity response, indicating the competitive nature of inhibition. The antagonists displayed a rank order of potency in antagonizing CCK's action on intestinal motility similar to their ability to antagonize CCK's action on pancreas and gallbladder. L-364,718 was the most potent antagonist, followed by CR1409, CR1505, CR1392, asperlicin, and proglumide. The antagonists did not affect contractile or myoelectrical responses to acetylcholine, histamine, motilin, or substance P. Thus compounds that have been described as CCK antagonists for pancreas and gallbladder also act as specific and competitive antagonists of CCK's action on contractile and myoelectrical activity of Heal and colonie muscle.     

The neuroendocrinology of stress and the pathophysiology and therapy of depression and anxiety

Clinical and preclinical studies have gathered substantial evidence that stress response alterations play a major role in the development of major depression, panic disorder, and post-traumatic stress disorder. The stress response, the hypothalamic pituitary adrenocortical (HPA) system and its modulation by corticotropin-releasing hormones (CRH),corticosteroids,and their receptors, and the roles of natriuretic peptides and neuroactive steroids are described. We review the role of the HPA system in major depression, panic disorder, and post-traumatic stress disorder and its possible relevance for treatment. Impaired glucocorticoid receptor function in major depression is associated with an excessive release of neurohormones such as CRH, to which a number of signs and symptoms characteristic of depression can be ascribed. In panic disorder, a role of central CRH in panic attacks has been suggested. Atrial natriuretic peptide (ANP) is causally involved in sodium lactate-induced panic attacks. Furthermore, preclinical and clinical data on its anxiolytic activity suggest that nonpeptidergic ANP receptor ligands may be potentially useful in the treatment of anxiety disorders. Post-traumatic stress disorder is characterized by a peripheral hyporesponsive HPA system and elevated CRH concentrations in the CSF. This dissociation is probably related to an increased risk of this disorder. We further review recent data that describe an important role of GABA(A)-receptor modulatory,3 alpha-reduced neuroactive steroids in major depression, anxiety, and its treatment. Antidepressants are effective in both depression and anxiety disorders and have major effects on the HPA system,especially on glucocorticoid and mineralocorticoid receptors. Normalization of HPA system abnormalities is a strong predictor of the clinical course, at least in major depression and panic disorder. Currently,CRH-R1 or glucocorticoid receptor antagonists and ANP receptor agonists are being studied and may provide future treatment options more closely related to the pathophysiology of these disorders.     

小胶质细胞和少突胶质细胞前体的培养和鉴定

目的 探讨新生大鼠脑组织小胶质细胞(MG)和少突胶质细胞(OL)前体的分离和体外培养方法 . 方法 取新生2 d SD大鼠脑组织,体外原代培养混合胶质细胞7 d后,分别采用"改良振荡伴差速贴壁"法和"营养缺失伴振荡"法纯化培养MG和OL前体,并分别应用免疫荧光染色异凝集素-B4(IB4)和OL前体标记物(O4)进行鉴定.结果 混合胶质细胞培养7 d后呈明显三层增长,其中MG位于上层,星型胶质细胞位于底层,两者之间为2型少突星型(O2A)祖细胞.纯化培养后OL前体胞体呈小圆形,有双极或三极突起,MG则以阿米巴形、圆形居多,或边缘呈毛刺状.免疫荧光染色IB4显示绿色荧光,MG纯度达到90%以上.免疫荧光染色O4显示棕黄色荧光,OL前体纯度达到95%以上. 结论 采用"改良振荡伴差速贴壁"法以及"营养缺失伴振荡"法分别成功获取大量纯度高、活力好的MG和OL前体.     

Review and meta-analysis of the phenomenology and clinical characteristics of mania in children and adolescents

OBJECTIVE: Using predetermined criteria for study quality and methods, a literature review and meta-analysis of seven reports about pediatric bipolar disorder (BPD) was conducted to determine if there is a consistent picture of the phenomenology and clinical characteristics of BPD in children and adolescents. METHODS: Searches were conducted in MedLine and PsycINFO using the terms mania, BPD, children and adolescents, and was limited to published articles in peer-reviewed journals. Seven reports were selected that met the following criteria: a systematic method for the elicitation and reporting of symptoms and clinical characteristics of subjects; subjects were interviewed by a trained researcher or clinician; ages 5-18 years; use of a diagnostic system, either DSM or RDC for categorization; a consensus method for the establishment of the diagnosis of BPD. RESULTS: Most DSM-IV symptoms of mania were common in the children and adolescents with BPD with the most common symptoms being increased energy, distractibility, and pressured speech. On average, four of five bipolar cases also showed threshold levels of irritable mood and grandiosity, and more than 70% of all cases showed elated/euphoric mood, decreased need for sleep, or racing thoughts. Roughly 69% of cases also showed poor judgment, whereas only half of bipolar cases demonstrated flight of ideas, and slightly more than one-third showed hypersexuality or psychotic features. CONCLUSIONS: The clinical picture that emerges is that of children or adolescents with periods of increased energy (mania or hypomania), accompanied by distractibility, pressured speech, irritability, grandiosity, racing thoughts, decreased need for sleep and euphoria/elation.