红藻氨酸致颞叶癫(癎)大鼠脑内Semaphorin3A、Semaphorin4C基因表达的研究

目的研究轴索导向分子Semaphorin3A(Sema3A)、4C(Sema4C)对癫大鼠海马苔藓纤维重建的调控作用及对皮层神经元的保护作用。方法大鼠侧脑室内注射红藻氨酸制备颞叶癫模型,原位杂交法检测致痫间后1d,1、2、3、4周大鼠脑内Sema3A/Sema4C mRNA表达。结果致痫间后1周Sema3A、Sema4CmRNA分别在齿状回(DG),CA3区表达明显下降(P<0.01),持续至3、4周时恢复至正常(P>0.05);致痫间后1d Sema3A mRNA在皮层表达明显下降(P<0.01),持续至1、2周后恢复至正常(P>0.05)。结论红藻氨酸致痫间后DG及CA3区神经元分别下调Sema3A/Sema4C mRNA的表达,促进癫大鼠苔藓纤维重建;皮层神经元通过下调Sema3A mRNA的表达来维持自身存活。     

癫痫持续发作时间与大鼠海马苔藓纤维发芽程度及自发性痫性发作的关系

目的探讨癫痫持续状态(SE)发作时间与致痫大鼠海马苔藓纤维发芽(MFS)程度及自发性痫性发作的关系。方法 104只雄性成年SD大鼠,随机分为对照组和3个SE实验组,建立氯化锂-重复低剂量匹罗卡品致痫大鼠模型;诱发SE30min(A组)、60min(B组)、90min(C组)后注射水合氯醛终止发作。各组大鼠自SE终止发作后于相同实验条件下普通饲养45d,观察大鼠行为及脑电图(EEG)的变化,记录自发性痫性发作的发生率。通过苏木精-伊红染色、Nissl染色和Timm硫化银组织化学染色方法观察各实验组海马MFS情况。结果氯化锂-重复低剂量匹罗卡品成功诱导大鼠SE的发生,发作程度均达Ⅳ级以上,EEG类似人类颞叶癫痫。80%的大鼠癫痫持续状态均发展为自发痫性发作,与SE时间无关。与对照组相比,实验A、B、C三组双侧海马CA3区均表现MFS(P0.05)。实验B组与A、C组相比,CA3区MFS明显增加(P0.05)。结论氯化锂-重复低剂量匹罗卡品可诱导SE,癫痫持续发作60min后终止的大鼠海马CA3区MFS明显增加,SE发作时间与海马MFS程度并不一定呈正相关。     

损伤性癫痫模型大鼠海马和额叶突触蛋白的动态表达

目的 通过观察FeCl2皮层注射致损伤性癫痫(PTE)模型大鼠海马、额叶突触蛋白P38的表达变化.探讨突触可塑性在PTE发病机制中的作用. 方法 健康成年雄性SD大鼠采用随机数字表法分为正常对照组(n=5)、假手术组(n=12)、模型组(n=20).采取立体定向皮层注射FeCl2(0.1 moL/L,10μL)建立PTE模型,假手术组注入等量生理盐水,正常对照组不做处理.观察各组大鼠EEG的变化并应用免疫组织化学方法 检测大鼠造模后不同时间点(1 h、7 d、14 d、30 d)海马、额叶P38的表达. 结果大多数模型组大鼠在注射FeCl2后不久记录到癫痫样放电;与假手术组比较,模型组不同时间点右侧额叶P38表达减少.差异有统计学意义(P<0.05);与正常对照组和假手术组比较,致痫1h后,CA3区多形层、辐射层、腔隙层和齿状回(DG)分子层P38表达均无明显变化,7 d后P38表达增加,维持到30d,差异均有统计学意义(P<0.05). 结论 与突触蛋白P38表达相关的突触可塑性变化在PTE的发病机制中可能起重要作用.     

N-myc在大鼠急性痫性发作模型中的表达及其意义

目的 探讨在氯化锂-匹罗卡品诱导大鼠急性痫性发作模型中N-myc表达及其意义。方法健康Wistar雄性大鼠45只，随机分为生理盐水对照组、地西泮干预组和致痫1h～9d组(根据致痫后的不同时点分7个组)，共9组，每组5只。采用氯化锂-匹罗卡品联合腹腔注射急性致痫大鼠模型，常规脏染色观察实验大鼠脑组织的形态学改变，免疫组化染色法观察脑内N—myc表达产物分布及其含量变化。结果 致痫1d～9d组尤其致痫6d和9d两组可见到脑组织损伤性改变，海马区重于皮质区。生理盐水对照组N—myc几乎无表达，地西泮干预组低表达，致痫组表达增多，尤其以致痫1d组和致痫3d组最为明显。结论 急性痫性发作或癫痫持续状态可导致脑组织损伤性改变，以海马结构等易损区为明显。N—myc表达及其表达量可能与急性痫性发作后脑损伤及其受累部位有关。     

颞叶癫(癎)大鼠海马轴突导向分子Sema3F及其受体Np2表达的变化

目的研究颞叶癫大鼠海马轴突导向分子Sema3F及其受体Np2表达的变化。方法给SD大鼠腹腔注射匹罗卡品、氯化锂制作颞叶癫模型。用免疫组化法和原位杂交技术对致后不同时间点大鼠海马CA1区、CA3区、齿状回的Sema3F mRNA、Np2 mRNA和蛋白表达进行检测,并与正常对照组比较。结果颞叶癫大鼠致后7d、15d,海马CA1区、CA3区Sema3F mRNA、Np2 mRNA和蛋白的表达明显低于正常对照组(P<0.05~0.01),致后30d、60d表达与正常对照组差异无统计学意义;而齿状回Sema3F mRNA、Np2 mRNA和蛋白的表达与正常对照组的差异无统计学意义。结论颞叶癫大鼠海马CA1区、CA3区Se-ma3F、Np2表达在致后早期明显下调,而在慢性期恢复正常。     

A型钾通道Kv4.1在戊四唑致痫大鼠海马区的表达

目的通过检测A型钾通道Kv4.1在戊四唑(PTZ)致痫大鼠海马CA1、CA3及齿状回区的表达变化,探讨A型钾通道在癫痫发病机制中的作用。方法 SD大鼠40只,随机分为正常组、致痫后1 h、24 h、72 h组。腹腔注射PTZ制备大鼠癫痫模型,应用免疫组化及Western Blot技术检测Kv4.1在各时间段海马CA1、CA3及齿状回区的蛋白表达情况。结果致痫组大鼠海马区Kv4.1蛋白表达水平在致痫后1 h、24 h、72 h三个时间段均明显高于正常组(P<0.05);各致痫组之间Kv4.1蛋白表达水平无明显差异(P>0.05)。结论大鼠癫痫模型海马区A型钾通道Kv4.1蛋白表达增多,Kv4.1的表达上调可能在癫痫的发生中起作用。     

低剂量伽玛刀照射对癫痫大鼠皮层及海马NMDA受体亚基表达的影响

目的观察低剂量伽玛刀照射对癫痫大鼠皮层和海马N-甲基-D-天氡氨酸(N-methyl-Daspartate,NMDA)受体亚基表达的影响。方法根据动物是否致痫及接受伽玛刀照射,将大鼠分为4组:对照组、伽玛刀组、药物致痫组、伽玛刀+药物组。腹腔连续注射戊四氮(pentylenetetrazole,PTZ)制备癫痫大鼠模型,以双侧额叶为照射靶区对大鼠进行低剂量伽玛刀照射,边缘剂量为15Gy。观察并记录各组大鼠伽玛刀照射前、后癫痫发作情况,并于伽玛刀照射后12周后留取脑组织,分别利用免疫组化及免疫蛋白印迹法对大鼠皮层及海马NMDA受体亚基NR1、NR2A和NR2B进行检测。结果对照组及伽玛刀组大鼠无痫性发作表现,与药物致痫组大鼠相比,伽玛刀+药物组大鼠经低剂量伽玛刀照射后12周,痫性发作明显减轻(P0.05)。与对照组相比,药物致痫组大鼠额叶皮层及海马CA1、CA3区NR1、NR2A和NR2B表达均明显增强(P0.05),阳性神经元数目及平均吸光度值均明显增加(P0.05);与药物致痫组比较,伽玛刀+药物组额叶皮层及海马CA1、CA3区NR1、NR2A和NR2B表达均明显降低(P0.05),阳性神经元数目及平均吸光度值明显减少(P0.05);伽玛刀组与对照组无明显差别(P0.05)。结论癫痫大鼠额叶皮层及海马NR1、NR2A及NR2B亚单位蛋白表达增强,低剂量伽玛刀照射可能引起癫痫大鼠皮层及海马NMDA受体亚基表达减少,这可能是低剂量伽玛刀抑制癫痫发作的分子机制之一。     

颞叶癫大鼠海马轴突导向分子Sema3F及其受体Np2表达的变化

目的 研究颞叶癫(癎)大鼠海马轴突导向分子Sema3F及其受体Np2表达的变化.方法 给SD大鼠腹腔注射匹罗卡品、氯化锂制作颞叶癫(癎)模型.用免疫组化法和原位杂交技术对致(癎)后不同时间点大鼠海马CA1区、CA3区、齿状回的Sema3F mRNA、Np2 mRNA和蛋白表达进行检测,并与正常对照组比较.结果 颞叶癫(癎)大鼠致(癎)后7 d、15 d,海马CA1区、CA3区Sema3F mRNA、Np2 mRNA和蛋白的表达明显低于正常对照组(P＜0.05～0.01), 致(癎)后30 d、60 d表达与正常对照组差异无统计学意义;而齿状回Sema3F mRNA、Np2 mRNA和蛋白的表达与正常对照组的差异无统计学意义.结论 颞叶癫(癎)大鼠海马CA1区、CA3区Sema3F、Np2表达在致(癎)后早期明显下调,而在慢性期恢复正常.     

海人酸致痫大鼠海马IL-1β、TNF-α的表达

目的 立体定向手术建立海人酸(KA)颞叶癫痫大鼠模型,检测海马内IL-1β、TNF-α蛋白及其mRNA的表达.方法 大鼠随机分为空白对照组、生理盐水对照组和模型组.模型组大鼠一侧海马CA3区注射KA (生理盐水组注射生理盐水),观察其行为学特征,HE染色和Nissl染色以及电镜观察其病理学改变,免疫组化法检测大鼠海马内IL-1β、TNF-α蛋白的表达,原位杂交法检测TNF-α mRNA的动态表达.结果 大鼠注射KA后出现湿狗样抖动、头面部肌阵挛、肢体阵挛及全面强直阵挛发作等,病理结果显示海马神经元变性、缺失及胶质细胞增生,模型组IL-1β在致痫后3 、6 h表达水平明显增加并于12 h达高峰,之后逐渐下降,7 d后与对照组相比差异无统计学意义(P＞0.05);TNF-α蛋白与mRNA表达时程基本一致,3 h出现,12 h达高峰,而后逐渐下降,7 d后回归至对照组表达水平,15 、30 d又高于对照组(P＜0.05).结论 (1)大鼠一侧海马注射KA是人类颞叶癫痫理想的动物模型;(2)内源性IL-1β、TNF-α参与了癫痫发病机制.     

A型钾通道Kv1.4在致痫大鼠海马区的表达

目的 通过检测A型钾通道Kv1.4在戊四唑(PTZ)致痈大鼠海马CA1、CA3及齿状同区的表达变化,探讨A型钾通道与癫痫发病的关系.方法 SD大鼠40只,随机分为对照组、致痫后1h、24h、72h组,每组各10只.腹腔注射PTZ制备大鼠癫痫模型,应用免疫组化及Western Blot技术检测Kv1.4在各时间段海马CA1、CA3及齿状回区的蛋白表达.结果 致痫组大鼠海马区Kv1.4蛋白水平在致痫后1h、24h、72h 3个时间段均明显低于正常组(P<0.05);各致痫组之间Kv1.4蛋白水平均无明显差异(P>0.05).结论 (1)A型钾通道Kv1.4在SD大鼠海马中广泛分布.表达丰富,以轴突处最为明显.(2)大鼠癫痫模型海马区A型钾通道Kv1.4蛋白表达减少,提示Kv1.4的表达下调可能与癫痫的发病相关.     

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.     

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.     

Learning and forgetting new names and objects in MCI and AD

We studied how subjects with mild cognitive impairment (MCI), early Alzheimer's disease (AD) and age-matched controls learned and maintained the names of unfamiliar objects that were trained with or without semantic support (object definitions). Naming performance, phonological cueing, incidental learning of the definitions and recognition of the objects were tested during follow-up. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, suggesting that the MCI patients’ preserved semantic memory can compensate for impaired episodic memory. The MCI group performed equally well as the controls in the tasks measuring incidental learning and recognition memory, whereas the AD group showed impairment in this respect. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that word learning is compromised in both MCI and AD, whereas long-term retention of newly learned words is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI.     

Necdin蛋白与神经元的生长分化

在神经系统 ,Necdin只在成熟神经元的细胞核中表达 ,可能与成熟神经元分裂静止状态的保持有关。近年的研究表明 ,Necdin是一种生长抑制蛋白 ,能与多种因子如SV4 0大T抗原 ,腺病毒E1A ,转录因子E2F1以及肿瘤抑制蛋白p5 3等结合 ,在功能上类似于成视网膜瘤蛋白Rb。necdin基因缺陷时 ,会引起脑内 ,特别是下丘脑神经元分化障碍。人类necdin基因位于PWS综合征的基因缺失区 ,可能与PWS的一些症状有关。本文从Necdin蛋白的基本概况 ,生物功能以及Necdin与疾病三个方面进行了综述     

Satellite cells and myonuclei in young and elderly women and men

The overall aim of this study was to assess the effects of aging on the satellite cell population. Muscle biopsies were taken from the tibialis anterior muscle of healthy, moderately active young (age range, 20-32 years; n = 31) and elderly (age range, 70-83 years; n = 27) women and men with comparable physical activity pattern. Satellite cells and myonuclei were visualized using a monoclonal antibody against neural cell adhesion molecule and counterstained with Mayer's hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for each individual. Compared with the young women and men, the elderly subjects had a significantly lower (P < 0.011) number of satellite cells per muscle fiber but a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The number of satellite cells relative to the total number of nuclei [satellite cells/(myonuclei + satellite cells)] was significantly lower in the elderly than in the young women and men. These results imply that a reduction in the satellite cell population occurs as a result of increasing age in healthy men and women.     

Necdin蛋白与神经元的生长分化

在神经系统,Necdin只在成熟神经元的细胞核中表达,可能与成熟神经元分裂静止状态的保持有关.近年的研究表明,Necdin是一种生长抑制蛋白,能与多种因子如SV40大T抗原,腺病毒E1A,转录因子E2F1以及肿瘤抑制蛋白p53等结合,在功能上类似于成视网膜瘤蛋白Rb.necdin基因缺陷时,会引起脑内,特别是下丘脑神经元分化障碍.人类necdin基因位于PWS综合征的基因缺失区,可能与PWS的一些症状有关.本文从Necdin蛋白的基本概况,生物功能以及Necdin与疾病三个方面进行了综述.     

Retrospective and prospective design and data

The study of the presentation, symptomatology and family characteristics of an exclusively adolescent sample of patients with borderline personality disorder (BPD) was undertaken. Twenty-four cases of borderline personality disorder, 20 females, 4 males, identified using chart review and meeting the criteria of the Diagnostic Interview for Borderlines (DIB) and DSM III-R, were matched with psychiatric controls. Adolescents with borderline personality disorder were found to have high rates of affective symptomatology with Axis I diagnosis of major depressive disorder - MDD (DSM-III-R), and high rates of interpersonal psychopathology, i.e., manipulation, devaluation, and a pervasive sense of boredom. The latter seem to be characteristic as for adults with borderline personality disorder. The families were particularly angry and volatile.     

Cortisol levels and depression in men and women using heroin and cocaine

Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender.     

相关性和一致性：这对相仿概念和测量方法的回顾与阐明

概述：一致性(agreement)和相关性(correlation)是两个广泛使用的概念,用来评估变量之间的关联。虽然二者相似且相关,但是它们代表关联完全不同的概念。评估变量之间的一致性假设变量测量的是相同的结构,而在变量测量完全不同的结构时也可以评估它们之间的相关性。这种概念上的差异就要求使用不同的统计方法,并且当评估一致性或相关性时,统计方法根据数据的分布和研究者的兴趣可能会有所不同。例如, Pearson相关性,作为评估连续变量之间相关性的一种普遍测量方法,只有用于符合线性关系的变量时才能提供有用的信息;当用于不符合线性关系的变量时就无法提供准确信息甚至会产生误导。同样地,内部相关性,作为一种评估连续变量之间一致性的常用方法,如果一致性不好的实质正好是研究兴趣所在,那么该测量就不能为研究者提供充分的信息。本报告回顾了一致性和相关性的概念,并讨论了几种常用方法在应用中的差异。