成瘾行为形成过程中学习记忆的参与及其相关的脑机制

多种学习记忆系统参与了成瘾行为形成的长时程适应过程.中脑奖赏通路腹侧被盖区-伏核投射多巴胺能神经纤维至前额叶、海马、杏仁核等有重要学习记忆功能的结构和核团,同时又接受这些区域发出的谷氨酸能传入纤维,提示多巴胺、谷氨酸等相对独立又互相关联的神经递质系统共同参与成瘾行为的学习记忆调控过程.不同的成瘾药物介导细胞外递质及相关受体作用,激活细胞内信号转导及基因的转录和表达,从而产生突触可塑性的变化.这一变化过程可能是成瘾行为获得和保持的主要生物基础.cAMP反应原件结合蛋白、即刻早基因ΔfosB可能是成瘾长时程适应的分子开关.     

成瘾行为形成过程中学习记忆的参与及其相关的脑机制

多种学习记忆系统参与了成瘾行为形成的长时程适应过程，中脑奖党通路腹侧被盖区－伏核投射多巴胺能神经纤维至前额叶，海马，杏仁核等有重要学习记忆功能的结构和核团，同时又接受这些区域发现的谷氨酸能传入纤维，提示多巴胺，谷氨酸等相对独立又互相关联的神经递质系统共同参与成瘾行为的学习记忆调控过程，不同的成瘾药物介导细胞外递质及相关受体作用，激活细胞内信号转导及基因的转录和表达，从而产生突触可塑的变化，这一变化过程可能是成瘾行为获得和保持的主要生物基础。cAMP反应原件结合蛋白、即刻早基因△fosB可能是成瘾长过程适应的分子开关。     

N-甲基D-天冬氨酸受体NR2B亚基与学习记忆关系研究进展

中枢神经系统N-甲基D-天冬氨酸受体（NMDAR）主要分布于中枢神经系统突触后膜等部位,对学习记忆的发生发展起着重要作用。其中,NMDA受体NR2B亚基在记忆的产生与维持及对记忆障碍的治疗有着深刻的意义。研究发现,NR2B亚基既可通过参与长时程增强（LTP）对学习记忆产生促进作用,亦可通过介导兴奋性氨基酸毒性作用导致神经功能损害,引起学习记忆障碍。故本文就NMDA受体NR2B亚基的分布、结构、功能及其与学习记忆的关系做一综述。     

GRIN2D相关发育性癫痫脑病的临床表型及突变功能异质性

正背景N-甲基-D-天冬氨酸(N-methyl-Daspartate,NMDA)受体是一类重要的离子型谷氨酸受体,主要表达于神经元的突触后膜,介导中枢神经系统兴奋性突触传递中的慢钙电流成分,与学习记忆、突触可塑性等生理功能及癫痫、发育迟缓、精神分裂症等多种神经系统发育性疾病有关。GRIN2D主要表达于胎儿时期及生后早期,其编码     

成年小鼠癫痫发作早期突触内、外N-甲基-D-天冬氨酸受体介导的电流变化

在癫痫疾病的发生和反复发作的过程中,N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体（NMDA受体）起着重要的作用。近年来的研究发现,突触内和突触外的NMDA受体在包括突触可塑性和细胞死亡的信号通路中起着不同的甚至是截然相反的作用。因此,我们在本研究中探讨了突触内、外NMDA受体介导的兴奋性突触后电流在癫痫发病的病理过程中的变化。我们利用氯化锂联合匹罗卡品（pilocarpine, PILO）诱导了成年癫痫小鼠模型,并在癫痫发作24小时后制作了急性海马切片,利用膜片钳全细胞记录法对CA1区锥体神经元的突触内、外NMDA受体电流进行了记录。我们发现,1）突触内NMDA受体电流的上升时间及衰减时间与对照组比较均无统计学差异;2）突触外NMDA受体电流的兴奋性电流峰值、面积峰值比、以及上升时间亦无统计学差异;3）但突触外电流的衰减时程相对于对照组加快。以上结果提示突触外NMDA受体可能参与癫痫的发病机制。     

离子型谷氨酸受体在长时程增强产生机制中的研究进展

长时程增强(Long-term potentiation,LTP)是一种发生在神经细胞信号传输中持久的增强现象。在分子水平研究学习和记忆能力,反应海马功能可塑性的长时程增强是常用的指标,其作用的改变与学习记忆密切相关。长时程增强增加会促进学习记忆能力,而长时程增强减弱会导致学习记忆能力的下降。诱导长时程增强发生的相关机制非常复杂,迄今尚未完全阐明,而关于离子型谷氨酸受体在其中的作用研究相对较少。因此,本文对离子型谷氨酸受体在长时程增强形成条件、分子机制等方面进行了综述。     

LTP的研究进展(Ⅰ)

LTP（长时程动作电位增强，或称长时程增强）是目前神经科学热点课题。各方面研究支持LTP与学习及记忆过程相关。基于其发生机制，LTP可分为NMDA受体及受体依赖性和Mossy fiber LTP两类。前一类由突触后NMDA受体激活，导致钙离子内流，钙浓度升高而引发，后一类则是蛋白激酶A活动引起突触前膜内钙离子浓度升高。结果神经递质释放增强，最终引起LTP。本概述了脑片技术对LTP研究的贡献，LTP发生与维持的相关因素，以及最新LTP研究的有趣发现。下期继续LTP话题，我们将介绍最近与LTP相关的BDNF（脑组织神经生长因子）及基因遗传学研究。     

脑源性神经营养因子在突触可塑性中的作用

脑源性神经营养因子(BDNF)作为神经营养因子家族中重要的一员,参与神经元的生长、发育、分化和维持。其在大脑中以前体蛋白和成熟体的形式表达,通过与神经细胞膜上不同的受体结合,激活多种信号通路引起突触的形态结构及长时程增强和长时程抑制的改变,从而对突触可塑性进行调节,对于改善学习记忆功能具有显著的疗效,已成为近年来神经科学和神经精神科学领域研究的重点内容。本文就BDNF的生物学特性和在突触可塑性中的作用做一综述。     

LTP研究进展(Ⅲ)——LTP和神经趋向因子

长时程增强（LTP）是学习和记忆过程的分子水平现象。参与LTP机制的因素很多，最近研究发现神经趋向因子，特别是其中的脑衍生的神经趋向因子（BDNF）对LTP起着重要的调节作用，而且对短时程及长时程突触可塑性均有影响。已经明确的神经趋向因子的功能包括调节神经分化，神经元轴突和树突的生长和修复，以及突触形成。本文综述了BDNF与LTP相关性的实验性根据。总结了BDNF通过突触前以及突触后机制影响LTP的引发和后期维持。BD-NF的直接作用机制是作用于突触前后膜上的受体，导致突触前递质小泡增多从而增加递质释放。在突触后引起突触后膜去极化，从而打开电压依赖性钙通道、征离子浓度增高，最终导致AMPA受体数目增多，功能强化，产生LTP。     

突触可塑性与学习记忆

突触是神经元与神经元之间结构和功能的接触点,是神经信息传递的关键部位,突触结构和功能的完整对于保证神经元获得信息并顺利进行信息传递、加工和贮存是非常重要的。突触可塑性是指突触在一定条件下通过改变形态而调整功能的能力,在神经系统的发育、成熟及学习记忆等众多的生理功能中起重要作用,具体表现为突触结合的可塑性与突触传递的可塑性。突触结合的可塑性指突触形态的改变以及新的突触联系形成和传递功能的建立,突触传递可塑性指突触的反复活动引起突触传递效率的增加(易化)或降低(抑制)。目前认为,突触可塑性和海马的长时程增强(long-term potentiation,LTP)密切相关,LTP反映突触水平的信息存储过程,是学习记忆的分子基础。结构是功能的基础,本文将针对突触结构参数的可塑性与LTP、学习记忆的关系进行综述。突触结构参数高等哺乳动物的中枢神经系统是以化学突触为主,经典的突触结构参数指标主要有突触界面类型及曲率、突触间隙宽度、突触小泡密度、突触后膜致密物厚度、突触前终扣面积、突触活性带长度、突触数密度等等。1、突触界面类型及曲率突触界面是指突触前成分与突触后成分相连接的面,也就是突触前膜与突触后膜隔着突触间隙相对应的...     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

几种治疗双相抑郁药物的疗效

尽管目前的统计数据表明双相躁狂与双相抑郁的患者数量相当，但大量的研究仍集中在双相躁狂的药物治疗上。例如，锂盐、卡马西平、丙戊酸盐都已经被证实对于治疗急性躁狂是有效的／[1-2／]。然而缺乏这些药物在治疗急性双相抑郁方面与安慰剂的对照研究。锂盐、抗癫痫药、抗抑郁药、非典型的抗精神病药物是临床常用的几种治疗双相抑郁药物，所以有必要将这几种药物在控制急性双相抑郁方面的疗效进行一下比较。     

高血压脑出血的显微外科治疗进展

高血压脑出血（Hypertensive intrac-rebral hemorrhage,HICH）是具有高发病率、高病死率、高致残率的急性脑血管疾病,占所有脑卒中患者的10%-20%,早期病死率可高达49.4%。随着人口老龄化,其发病率逐年提高;而外科手术的干预,使其病死率有所下降,但致残率居高不下。如何提高手术疗效和患者生存质量,一直是神经外科医师努力的方向。微侵袭血肿清除术因其手术创伤小,恢复快,是目前国内治疗高血压脑出血的重要手段。     

Effects of natural-cerebrolysin-containing serum on neurotoxicity and synaptogenesis in amyloid-beta 1-40-induced Alzheimer’s disease in vitro models

BACKGROUND： Neuronal loss, synapse mutilation, and increasing malnourished axons are pathologically related to Alzheimer＇s disease. Microtubule-associated protein 2 （MAP2） is of importance for neuronal, axonal, and dendritic generation, extension, and stabilization, as well as for the regulation of synaptic plasticity.
OBJECTIVE： To investigate the antagonistic effects of natural-cerebrolysin-containing serum on beta amyloid protein 1-40 （Aβ1-40）-induced neurotoxicity from the standpoints of cell proliferation, synaptogenesis, and cytoskeleton formation （MAP2 expression）. DESIGN, TIME AND SETTING： A paralleled, controlled, neural cell, and molecular biology experiment was performed at the Institute of Integrated Chinese and Western Medicine, Shenzhen Hospital, Southern Medical University between February 2006 and April 2008.
MATERIALS： PC12 cells, derived from the rat central nervous system, were purchased from Shanghai Institute of Cell Biology, Chinese Academy of Sciences, China. A β1-40 was provided by Sigma, USA. Natural-cerebrolysin was provided by Shenzhen Institute of Integrated Chinese and Western Medicine, China. The natural-cerebrolysin was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae）, and Yixingye （Ginkgo Leaf） in a proportion of 1：2：2. Following conventional water extraction technology, an extract （1：20） was prepared. Each gram of extract equaled 20 grams of crude drug. In a total of 12 adult male New Zealand rabbits, six underwent intragastric administration of natural-cerebrolysin extract for 1 month to prepare natural-cerebrolysin-containing serum, and the remaining six rabbits received intragastric administration of physiological saline to prepare normal blank serum.
METHODS： An AIzheimer＇s disease in vitro model was induced in PC12 cells using Aβ1-40. The cells were incubated with varying doses of natural-cerebrolysin-containing serum （2.5%, 5%, and 10%）. Normal blank serum-treated PC12 cells served as a blank control group.
MAIN OUTCOME MEASURES： Through the use of inverted phase contrast microscope, cell morphology and neurite growth were observed, neurite length was measured, and the percentage of neurite-positive cells was calculated. Cell proliferation rate was determined by MTT assay, and MAP 2 expression was detected by fluorescent immunocytochemistry.
RESULTS： Following Aβ1-40 treatments, some PC12 cells were apoptotic/dying, and only a few short neurites were observed. Following interventions with natural-cerebrolysin-containing serum, the PC12 cells proliferated, there was an increased number of neurites, and neurite length was enhanced. After middle- and high-dose natural-cerebrolysin treatments, the percentage of neurite-positive cells, as well as the average length of neurites, was significantly greater than the normal blank serum-treated PC12 cells （P 〈 0.05 or P 〈 0.01）. Compared with the blank control group, MAP2 expression in the Aβ1-40-treated PC12 cells was significantly inhibited, and the cell proliferation rate was significantly decreased （P 〈 0.01）. Following incubations with natural-cerebrolysin-containing serum, MAP2 expression and cell proliferation rate in the PC12 cells were significantly increased in a dose-dependent manner, compared with treatments with blank control serum （P 〈 0.05 or P 〈 0.01 ）.
CONCLUSION： Natural-cerebrolysin exhibited antagonistic effects on neurotoxicity in Aβ1-40 induced Alzheimer＇s disease in vitro models. These effects were likely related to cell proliferation and the upregulation of intracellular MAP2 expression.     

神经内镜联合亚低温治疗高血压基底节区脑出血

目的 探讨神经内镜联合亚低温在治疗高血压基底节区脑出血中的临床应用价值.方法 回顾性分析我院神经内镜治疗高血压基底节区脑出血患者40例的临床资料,并对治疗结果进行分析.结果 神经内镜治疗组22例(甲组),神经内镜联合亚低温治疗组18例(乙组),术后3个月根据GCS评分,甲组恢复良好1例,中残4例,重残6例,植物生存6例,死亡5例;乙组恢复良好4例,中残8例,重残3例,植物生存1例,死亡2例,两组比较差异有统计学意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组颅内压明显降低.结论 神经内镜是治疗高血压基底节区脑出血较为有效的手术方式,联合亚低温治疗能有效降低颅内压,改善术后神经功能恢复,具有较好的临床应用价值.     

Total saponins of Panax ginseng effects on proliferation and differentiation of human embryonic neural stem cells and in a Parkinson’s disease mouse model

BACKGROUND： Total saponins of Panax ginseng （TSPG） exhibits neuroprotection against Parkinson＇s disease in the substantia nigra. OBJECTIVE： To investigate the effects of TSPG on human embryonic neural stem cells （NSCs） proliferation and differentiation into dopaminergic neurons using in vitro studies, and to observe NSC differentiation in a mouse model of Parkinson＇s disease, as well as behavioral changes before and after transplantation. DESIGN, TIME AND SETTING： In vitro neural cell biology trial and in vivo randomized, controlled animal trial were performed at the Institute of Basic Medical Sciences, Chongqing Medical University between September 2004 and December 2007. MATERIALS： TSPG （purity 〉 95%） was isolated, extracted, and identified by Chongqing Academy of Chinese Materia Medica. Recombinant human basic fibroblast growth factor （bFGF） and recombinant human epidermal growth factor （EGF） were purchased from PeproTech, USA. A total of 25 C57/BL6J mice, aged 18-20 weeks were included. Twenty were used to establish a Parkinson＇s disease model with i.p. injection of MPTP （1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine） and TSPG alone or combined with interleukin-1 （IL-1）-treated NSCs prior to transplantation into the corpus striatum. The remaining five mice were pretreated for 3 days with TSPG prior to MPTP injection, serving as the TSPG prevention group. METHODS： Primary NSCs were isolated, cultured and purified from embryonic cerebral cortex. Immunocytochemistry was employed to detect specific antigen expression in the NSCs. In vitro experiment： （1） to induce proliferation, NSCs were treated with TSPG, EGF＋bFGF, or TSPG＋EGF＋bFGF, respectively; （2） to induce dopaminergic neuronal differentiation, NSCs were treated with TSPG, IL-1, or TSPG＋IL-1, respectively. MAIN OUTCOME MEASURES： In vitro experiment： the effects of TSPG on NSCs proliferation were evaluated with flow cytometry and MTT assay. Tyrosine hydroxylase expression was determined by immunocytochemistry assay to observe effects of TSPG on dopaminergic neuronal differentiation. In vivo experiment： differentiation of grafted NSCs in the mouse brain was determined by immunohistochemical staining. Behavioral changes were evaluated by spontaneous activity frequency, memory function, and score of paralysis agitans. RESULTS： （1） NSCs were cultured and passaged for more than three passages. Immunocytochemistry revealed positive nestin staining, as well as neurofilament protein and glial fibrillary acidic protein. （2） TSPG significantly increased NSC proliferation, in particular when combined with EGF and bFGF, which was twice as effective as FGF or bFGF alone. TSPG also induced dopaminergic differentiation in NSCs, in particular when TSPG was added together with IL-1, resulting in an effect five times greater than that of IL-1 alone. （3） At day 30 following transplantation, most NSCs in the TSPG prevention group differentiated into dopaminergic neurons, and the scores of paralysis agitans, spontaneous activity, and memory function were significantly increased compared with TSPG alone or TSPG＋IL-1 groups （P 〈 0.05）. CONCLUSION： TSPG stimulated NSC proliferation, in particular when combined with FGF and bFGF. TSPG significantly induced dopaminergic neuronal differentiation of NSCs, and the effect was greater when combined with IL-1. In addition, TSPG greatly improved behavior in the Parkinson＇s disease mouse model following NSC transplantation. Following NSC transplantation, TSPG pretreatment exhibited superior efficacy over either TSPG alone or TSPG in combination with IL-1, in terms of behavioral improvements in the Parkinson＇s disease mouse model.     

Wnt信号通路与骨髓间充质干细胞增殖及分化的关系

骨髓间充质干细胞（bonemarrow—derived mesenchymal stem cells,BMSCs）是骨髓中不同于造血干细胞的一类细胞,其来源丰富,取材简便,易分离、纯化、培养,在一定的条件下可以迅速体外扩增,具有多向分化潜能,可以通过不同的方法被诱导分化成骨细胞、软骨细胞、肌细胞、神经胶质细胞、神经元细胞等,而且它具有低免疫源性,向病变部位迁移的能力,