大白鼠神经垂体的超微结构及其联系

本文用电子显微镜技术,对大白鼠神经垂体的超微结构进行了研究。结果除证实神经分泌物质在神经末梢内贮存并释放人血液外,还显示在神经分泌末梢之间存在着轴-轴突触样结构;在神经分泌末梢与垂体细胞之间,存在着神经-胶质突触样连接;在垂体细胞之间,存在着中间连接。轴-轴突触和神经-胶质突触样连接的特点是:1.突触前、后膜呈不显著的增厚;2.突触前成分内,有成群的微泡靠近并附着于突触前膜;3.突触间隙为20 nm左右,内含多少不等的电子致密物质。作者认为,以上两种突触样结构和垂体细胞,均与神经分泌物质释放的调节有关。     

SNARE和synaptotagmin对学习记忆作用的研究进展

可溶性NSF附着蛋白受体(SNARE)复合物是神经元囊泡胞吐过程重要的一部分,一般认为它参与调节突触前膜融合过程。SNARE复合体核心蛋白主要有3个,突触小体相关蛋白(SNAP-25),syntaxin和囊泡相关蛋白(VAMP)。突触结合蛋白(synaptotagmin,syt)是一个钙感受器蛋白,通过和SNARE结合起到调控膜融合过程的作用。SNARE复合物中的syntaxin,SNAP-25以及syt基因的缺失可造成小鼠认知以及学习记忆损伤。本文主要综述两者在突触前膜的作用过程,并分析其对学习记忆的影响与其调节突触前膜融合过程密切相关,以期了解syntaxin,SNAP-25及syt影响学习记忆的分子机制。     

可卡因对多巴胺能神经元的作用及机制

可卡因主要作用于单胺类转运体,包括多巴胺转运体(DAT)、5-HT转运体(SERT)和去甲肾上腺素转运体(NET),阻止这些转运体将突触前释放的神经递质转运回突触前膜神经末梢,从而增强单胺能神经递质的作用而产生精神兴奋效应,其中DAT是可卡因作用的主要环节。可卡因也能够增加突触前末梢神经递质的释放,对突触后神经元的基因和蛋白水平的调节在可卡因成瘾中的作用也是不可忽视的。本文就可卡因成瘾分子机制的最新研究进展作一综述。     

KA受体的研究进展

以往对于KA受体的分子特性及生理功能所知甚少。近年来 ,分子生物学及药理学技术的发展大大加快了对KA受体的研究进程。迄今为止 ,已经克隆出五种KA受体的亚型 (GluR5 ,GluR6 ,GluR7,KA1,KA2 ) ,每种亚型大约由 90 0个氨型酸组成 ,他们广泛的分布于中枢和外周神经系统内 ,不仅存在于突触前膜调节神经递质的释放 ,而且存在于突触后膜在突触传递中发挥作用此外 ,KA受体有望成为研发抗癫痫和镇痛药物的新的靶目标。     

侧脑室注射链脲佐菌素对大鼠海马神经元突触的影响

为观察链脲佐菌素(streptozotocin,STZ)双侧侧脑室注射对大鼠海马神经元突触的影响,本研究将Wistar大鼠随机分为对照组和模型组,模型组大鼠分别于第1、3d双侧侧脑室重复注射STZ3mg/kg,对照组以人工脑脊液代替STZ。21d后,取大鼠海马,免疫组织化学染色及Western blotting方法观察突触素、活性调节细胞骨架相关蛋白(activity-regulated cytoskeletal-associatedprotein,Arc)的表达;电镜观察海马CA1区神经元突触超微结构的改变。结果显示:与对照组相比,模型组大鼠海马内突触素蛋白表达显著减少,而Arc蛋白表达显著增多;模型组海马CA1区神经毡内突触结构异常,突触小泡聚集增多。以上结果提示:脑室注射STZ可影响大鼠海马突触相关蛋白的表达,引起突触超微结构异常,干扰了神经元突触信号的传导。     

突触体素

突触体素（synaptophysin）是突触小泡膜上的一种含糖的膜结构蛋白。1985年，Jahn等[1]首先在大鼠脑中发现，因为它的分子量是38kD，所以Jahn等称之为P38。同年，德国肿瘤研究中心的Wieden－mann等o］在牛脑中也发现并且提纯了这种蛋白，把它命名为spoptophysin，周国民等［’］将之译为突触囊泡蛋白，吴偿等’‘增译为突触生长素，现在多译为突触体素。穷触体素一经发现，就曾引起人们的关注，一些学者应用识别突触体素的单克隆抗体SY38，在许多脊椎动物和非脊椎动物的中枢和周围神经系统的几乎所有被观察的神经终未内均发现有穷触体素…     

大鼠脑内突触后致密物蛋白质的提取及鉴定

目的 提取纯度高、易分离溶解的突触后致密物（PSD）蛋白质。方法 应用蔗糖密度梯度离心法,逐次获取P2,突触小体和PSD-1;应用Western blot检测PSD-1蛋白质的纯度;对PSD-1运用膜顺序提取法获取可溶性蛋白PSD-2;应用双向凝胶电泳技术分离PSD-1与PSD-2蛋白质点,PDQuest软件分析比较其数目差异。结果 突触后标志分子PSD-95在P2成分、突触体和PSD-1 3组成分中均呈免疫染色阳性,而突触前标志分子突触素在PSD-1成分中呈免疫阴性。从PSD-1蛋白中电泳分离到286±25个蛋白质点而显著低于从PSD-2中分离到720±17个蛋白质点 (P<0.01)。结论 蔗糖密度梯度离心联合膜顺序提取法可获得纯度高、易分离溶解的的PSD蛋白质。     

突触体素及癫痫发作后的突触重塑

突触体素(synaptophysin,SYN)是一种广泛存在于突触前囊泡膜上的钙结合糖蛋白,与突触的结构和功能密切相关。因其相对分子量为38KD,所以也简称为P38蛋白。1985年,Jahn等[1]和Wiedenmann等[2]先后在大鼠脑和牛脑内的突触前囊泡膜上发现此糖蛋白,命名为synaptophysin。研究表明,S     

突触相关蛋白102的结构、功能及相关研究进展

突触相关蛋白102（SAP102）是突触后膜区域中一种重要的支架蛋白,属于膜相关鸟苷酸激酶家族（MAGUK）,在新生和成熟的神经元中均有高表达。SAP102有助于特化结构域的受体,如N-甲基-D-天冬氨酸（NMDA）受体和α-氨基-3羟基-5甲基-4异恶唑（AMPA）受体和通道蛋白定位在特定膜区域上,并在囊泡内NMDA受体簇的胞质运输过程中起重要的调节作用。此外,SAP102还可参与调节皮质突触的发育。SAP102的表达或功能异常与多种疾病,如阿尔茨海默病与精神分裂症等的发生发展相关。尽管SAP102与神经系统正常生理功能及某些疾病关系密切,但目前人们对SAP102的认识尚不够充分,我们将对SAP102蛋白的结构、生理功能及与之相关疾病的研究进展进行综述。     

TRPV1通道在中枢神经系统中的功能

TRPV1(transient receptor potential vanilloid 1)是在机体广泛分布的非选择性阳离子通道,能被氢离子、高温以及其它内源性和外源性配体激活.其在外周神经系统中主要参与伤害性高温的感受以及痛觉过敏等生理机制.TRPV1在中枢神经系统中功能的研究进展主要体现在突触传递,体温调节,痛觉的调制和细胞凋亡等方面.TRPV1的激活降低突触前谷氨酸的释放及增强已存在的突触后AMPA受体的作用,从而增强了突触传递效能.外周的TRPV1通过激活能够抑制血管的收缩和生热作用,从而抑制体温的升高,当TRPV1被阻断时就发生体温过高,而TRPV1体温调节的中枢作用机制可能是通过直接作用于体温调节中枢.脑干的痛觉调制环路的激活TRPV1可以引起谷氨酸盐的释放,进而激活突触后I类mGlu受体以及NMDA受体,从而起到镇痛的功能.另外近年发现TRPV1在中枢也参与呕吐、呼吸、心率及血压的调节.     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

即早基因c-fos与脑血管病及学习记忆

即早基因c-fos是广泛存在于原核细胞和真核细胞的高度保守基因.在正常情况下,c-fos基因参与细胞生长、分化、信息传递、学习和记忆等生理过程,而在病理情况下c-fos基因表达及调控变化与多种疾病的发生和发展有关.C-fos在中枢神经系统的某些部位可有基础水平的表达,但表达很低,当受到如脑缺血、脑出血、痫性发作、应激等刺激后,其在数十分钟内做出反应,在对外界刺激-转录耦联的信忠传递过程中起着核内第三信使的重要作用.     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.