抗LINGO-1干预促髓鞘重塑在认知损伤中的应用可能

LINGO-1选择性表达于中枢神经系统(central nervous system,CNS)的少突胶质细胞、少突胶质细胞前体细胞和神经元,在髓鞘损伤性疾病和动物模型中表达升高,通过活化RhoA和抑制Akt磷酸化负性调节少突胶质细胞分化和髓鞘化、神经元存活和轴突再生。抑制LINGO-1功能可有效改善脱髓鞘损伤,维持神经元成活。髓鞘与认知功能关系密切,大量证据表明其损伤可能引起认知功能异常,本综述拟总结抗LINGO-1促髓鞘重塑研究进展并探讨其在认知损伤中应用的可能。     

波形蛋白的分子结构和表达及其病理学意义

中间丝蛋白(Intermediate Filament Protein, IFP)共有五种类型:角蛋白(Keratin, K)、结蛋白(Desmin, Des)、波形蛋白(Vimentin, Vim)、胶质纤维酸性蛋白(CFAP)及神经微丝(NF)。历来认为它们分别特异地存在于不同起源的细胞中,其中Vim存在于间叶起源的细胞中。近年来,进一步的研究发现,IFP之间在分子     

巢蛋白的表达模式及其功能

巢蛋白 (Nestin)属于第Ⅵ类中间丝蛋白 ,主要由胚胎期和成年的神经前体细胞一过性表达 ,在中枢神经系统各种损伤条件下 ,脑中反应性星形胶质细胞和神经元又再现其表达。然而 ,本实验室首次观察到 ,在正常成年大鼠和成人基底前脑存在一个有别于胆碱能神经元的Nestin免疫反应阳性神经元簇 ,并证明了这些Nestin -IR神经元的Nestin表达受卵巢雌激素的影响。Nestin的功能与维持神经前体细胞的正常形态结构有关 ,也可能与其它的中间丝蛋白如神经丝共聚形成多聚体 ,此外 ,尚可能在影响其它蛋白的功能方面发挥作用。     

波形蛋白在细胞内外的不同功能与相关病理

<正>真核细胞骨架是由微管、微丝、中间丝(Intermediate filaments,IFs)构成的蛋白纤维网状支架系统。IFs根据基因序列分为六种类型,不同类型中间丝的表达具有明显的组织细胞特异性。波形蛋白(Vimentin,Vim)为Ⅲ型中间丝蛋白,主要表达于中胚层起源的间充质细胞中,如成纤维细胞、内皮细胞、中性粒细胞、巨噬细胞等。Vim在感染、肿瘤、自身免疫、固有免疫等多方面显现复杂的功能特性。     

小胶质细胞生物学特性及对神经元调控作用

小胶质细胞是常驻脑实质内免疫细胞,在生理状态下是高度动态的,表达多种免疫受体与神经递质受体,严格监控着中枢神经系统(CNS)微环境。近来大量研究揭示这类免疫细胞具有积极地调控神经元作用,其潜在的影响了神经元发生、突触修剪,调节突触可塑性,阻止神经毒性。小胶质细胞功能性变化对CNS的发育、成熟及退化有重要作用。     

慢病毒介导的RNA干扰通过下调白细胞介素6抑制损伤后 星形胶质细胞中波形蛋白的表达

目的：探讨用慢病毒介导的RNAi方法抑制白细胞介素6（ IL-6）,观察其对损伤后星形胶质细胞中波形蛋 白（ Vim）表达的影响。方法：选取3 日龄SD大鼠的大脑皮质,体外培养星形胶质细胞,分为载体组和病毒组, 2 组均制备细胞划伤模型,采用qRT-PCR 检测Vim mRNA的表达,免疫印迹检测Vim蛋白表达,用免疫荧光检测 Vim的定位,MTT检测划伤模型中星形胶质细胞增殖率,免疫荧光检测GFAP用于观察划伤模型中星形胶质细胞 活性。结果：划伤细胞2 d 后,病毒组的Vim mRNA和蛋白表达量较载体组明显下降。Vim主要在星形胶质细胞 胞质中表达。病毒组中星形胶质细胞增殖情况和活性低于载体组。结论：用慢病毒介导的RNAi方法抑制炎症因 子IL-6,可以下调反应性胶质化细胞中Vim的表达,影响星形胶质细胞胶质化反应,可能抑制胶质瘢痕形成,对 神经细胞的再生具有积极作用。     

小胶质细胞的免疫功能

小胶质细胞是常驻中枢神经系统单核吞噬细胞家族的成员之一。他们与巨噬细胞有许多相同的功能和表形特征 ,参与脑内的固有免疫反应 ,而且能早于外周白细胞的渗透成为CNS抵御病原体入侵的第一防线。小胶质细胞也能作为抗原提呈细胞 ,刺激T细胞活化、增殖。小胶质细胞可以产生多种细胞因子和趋化性细胞因子启动或促进炎症反应在CNS内的进程 ,也能够表达许多细胞因子受体和趋化性细胞因子受体 ,这些受体的平衡在诱导和调节小胶质细胞的免疫功能上起到决定性作用。而且 ,小胶质细胞也能受到神经元的调控 ,以阻止过度的免疫反应对神经元的损害。     

鉴定干细胞及描述已分化细胞类型特征时的常用标志(二)

神经系统CD1 33神经干细胞、HSC 识别神经干细胞的一种细胞表面蛋白 ,神经干细胞可形成神经元和神经胶质细胞。胶质纤维酸性蛋白 (glialfibrillaryacidicprotein ,GFAP) 星形胶质细胞星形胶质细胞特异性产生的一种蛋白。微管相关蛋白 2 (microtubule associatedprotein 2 ,MAP 2 ) 神经元 树突特异性的MAP ,是神经元树突上发现的一种特异性蛋白。髓鞘碱性蛋白 (myelinbasicprotein ,MPB) 少突胶质细胞 由成熟少突胶质细胞产生的一种蛋白 ,位于包绕神经元结构的髓鞘中。巢蛋白 (nestin)神经祖细胞原始神经组织表达的一种中间丝结构…     

小胶质细胞的免疫功能

小胶质细胞是常驻中枢神经系统单核吞噬细胞家族的成员之一。他们与巨噬细胞有许多相同的功能和表形特征，参与脑内的固有免疫反应，而且能早于外周白细胞的渗透成为CNS抵御病原体入侵的第一防线。小胶质细胞也能作为抗原提呈细胞，刺激T细胞活化、增殖。小胶质细胞可以产生多种细胞因子和趋化性细胞因子启动或促进炎症反应在CNS内的进程，也能够表达许多细胞因子受体和趋化性细胞因子受体，这些受体的平衡在诱导和调节小胶质细胞的免疫功能上起到决定性作用。而且，小胶质细胞也能受到神经元的调控，以阻止过度的免疫反应对神经元的损害。     

Olig家族在中枢神经发育和损伤中的作用

<正>Olig家族广泛表达于各种生物的中枢神经系统(centralnervous system,CNS)中,在决定神经干细胞(neural stemcells,NSCs)分化成熟过程中起了关键性作用,精确调控着神经元和胶质细胞的分化亚型。近年发现它还广泛参与了CNS损伤的修复过程。本文试从Olig家族概述,Olig家族与CNS发育的关系以及Olig家族参与CNS损伤修复的情况进行综述。     

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.