神经元轴突电刺激响应的有限元数值模拟

为了研究神经元轴突的微观生理电传导特性,建立了神经元轴突的三维有限元模型,通过数值计算模拟神经元轴突对电刺激的动态响应.建立海马神经元轴突的三维几何模型并指定其生物物理参数,根据Hodgkin-Huxley方程和Maxwell方程,建立偏微分方程组,对神经元轴突有限元模型施加不同持续时间和不同脉冲幅度的电流脉冲并求解,获得神经元轴突的三维电势分布和动作电位曲线.数值模拟结果显示,该神经元轴突的静息电位约为-65 mV;对模型施加持续时间为2 ms,强度0.01 A/m2的电流脉冲刺激未产生动作电位,施以(2 ms、0.2 A/m2),(20ms、0.01 A/m2),(20ms、0.2 A/m2)脉冲刺激均产生动作电位,峰值分别出现在0.012 s、0.017 s和0.012 s,动作电位幅度约为100mV,持续时间约为2 ms.神经元轴突电刺激响应的有限元模拟结果与实验结果吻合,表明所建立的神经元轴突有限元模型及数值模拟方法合理、可靠,为深入研究神经电生理特性提供了基础模型和仿真分析方法.     

轴突转运障碍与阿尔茨海默病

指出了一个神经元依靠其特有的分支与其他神经元形成连接并构成功能回路,确保神经信号的传递和实现神经功能,轴突转运对确保神经元的结构和功能非常重要.研究表明:微管、分子马达和其他辅助因子的协调和整合为轴突转运功能的实现提供了重要的分子基础.大量研究发现:轴突转运功能障碍与阿尔茨海默病的起因和进展有重要的关系,简要综述了目前研究进展,对轴突转运障碍与阿尔茨海默病发病之间的关系进行了阐述.     

微管剪切蛋白调控果蝇节律神经元的形态发育

Spastin、Katanin60和Fidgetin是3种重要的微管剪切蛋白,它们的突变会导致神经退行性疾病。然而,这些微管剪切蛋白如何调节神经元的形态和功能尚不明确。果蝇的昼夜节律行为主要受位于大脑腹外侧的4对神经元LNv的控制。LNv神经元具有简单的形态,并且其轴突末梢会随着昼夜节律而伸缩。本研究利用LNv神经元作为模型,探讨不同微管剪切蛋白在神经元形态发育中的功能差异。我们发现,在LNv神经元中组成性表达Spastin会导致轴突和树突的发育异常,并且抑制神经肽PDF的转运;在成虫时期特异性表达Spastin会引起神经纤维的退化。而在LNv神经元中过量表达Katanin60或Fidgetin则不会影响LNv神经元的形态和神经肽PDF的转运。我们的结果揭示了不同微管剪切蛋白在不同神经元中具有不同的功能特性。     

日本弓背蚁(Camponotus japonics)中脑前端超微结构观察

应用常规电镜技术,对日本弓背蚁中脑前端超微结构进行了观察,结果发现:(1)日本弓背蚁中脑前端存在两种细胞,一种是以圆形、卵圆形为主的圆形局部神经元,其细胞核、核仁、线粒体、质膜等细胞器清晰可见;另一种是以长椭圆形为主的长椭圆形局部神经元,电镜下可观察到其细胞核、核仁及其他细胞器,但不如圆形局部神经元典型.(2)中脑前端髓质中包含大量神经束,轴突、树突(棘)纵横交错其中,形成各种突解联系.突触多以轴-树突触和轴-轴突触为主,亦可见树-树突触.     

中枢髓鞘源性抑制蛋白与中枢神经再生

Nogo是一类中枢髓鞘源性抑制蛋白,主要由少突胶质细胞表达,是抑制中枢神经元轴突再生的抑制因子。这些研究成果为探讨CNS损伤的治疗提供了新思路。论文综述了Nogo的结构及在CNS中对神经元轴突再生的抑制作用。     

绘简图进行神经传导路教学

神经系统基本的活动形式是反射 .简单的反射只包括两个神经元 ,即传入神经元和传入神经元 ,复杂的反射则有多个神经元参加 ,即传入神经元和传出神经元之间增加一些中间神经元 (中间神经元位于中枢神经系统内 ,其轴突有的组成长距离的纤维束 ) .复杂的反射活动是由传入神经元、中间神经元和传出神经元互相借突破触联接而成的神经元链 ,其特点是传导路径长 ,有传入、传出之分 ,多半要涉及最高级神经中枢—大脑皮质 ,这样的神经传导通路称传导路 .体育专业学生在学习传导路知识时 ,往往会对各传导路记错搞混 ,甚至张冠李戴 .在几年的教学实践中…     

MYRF与中枢神经系统髓鞘发育

在脊椎动物的中枢神经系统中,少突胶质细胞围绕神经元轴突形成髓鞘,使神经冲动可以沿轴突跳跃式快速传导.髓鞘的异常会导致多种神经系统疾病甚至引起死亡.MYRF作为一种转录因子,是目前已知的OLs分化和髓鞘维持的最关键调控因子之一,对MYRF的研究将是髓鞘发育和再生机制的重要内容.文章就近年来MYRF调控中枢神经系统髓鞘发育的研究进展进行了总结.     

核孔蛋白Seh1通过招募Olig2和Brd7促进少突细胞分化和髓鞘生成

<正>在中枢神经系统中,少突胶质细胞(oligodendrocytes,OLs)形成髓鞘包裹神经元轴突,从而促进神经信号的快速传导.髓鞘缺失会减慢神经信号传导并影响神经元的存活,导致神经系统疾病,如多发性硬化症和视神经脊髓炎等.在多发性硬化症患者的髓鞘损伤区,存在许多少突胶质细胞前体细胞(oligodendrocyte     

生长锥细胞骨架的运动

神经组织是神经元树突和轴突通过突触连接形成的神经纤维网络,而树突和轴突之所以能准确到达其特定靶结构并与之建立结构和功能联系则取决于突起末端生长锥的运动.生长锥能依据周围环境的生长和导向信号而改变自身的形状,具有高度的能动性.其动力来源在于其本身微管和微丝丰富而准确的运动,无论是突起的生长,还是其损伤后的再生,生长锥内微管和微丝的不断聚合和解聚,二者相互作用并不断发生独特的空间和位置变化,从而改变生长锥的生长行为,以及神经元的形态和它们之间形成的网络结构.对生长锥细胞骨架工作模式的认识,有助于理解突起的生长和再生过程.     

电压门控钠离子通道:律动生命乐章的主音符

生命个体传递神经冲动时扩布的电位变化过程以动作电位发放形式为特质表征.电压门控钠离子通道 (voltage-gated sodium channels,VGSCs)是形成动作电位的核心蛋白构件,在细胞的电兴奋产生和律动中起主角作用.VGSCs决定神经元细胞的兴奋性以及从突触输入到轴突输出的信号传导过程.VGSCs也是众...     

Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein

Adult mammalian axon regeneration is generally successful in the peripheral nervous system (PNS) but is dismally poor in the central nervous system (CNS). However, many classes of CNS axons can extend for long distances in peripheral nerve grafts. A comparison of myelin from the CNS and the PNS has revealed that CNS white matter is selectively inhibitory for axonal outgrowth. Several components of CNS white matter, NI35, NI250(Nogo) and MAG, that have inhibitory activity for axon extension have been described. The IN-1 antibody, which recognizes NI35 and NI250(Nogo), allows moderate degrees of axonal regeneration and functional recovery after spinal cord injury. Here we identify Nogo as a member of the Reticulon family, Reticulon 4-A. Nogo is expressed by oligodendrocytes but not by Schwann cells, and associates primarily with the endoplasmic reticulum. A 66-residue lumenal/extracellular domain inhibits axonal extension and collapses dorsal root ganglion growth cones. In contrast to Nogo, Reticulon 1 and 3 are not expressed by oligodendrocytes, and the 66-residue lumenal/extracellular domains from Reticulon 1, 2 and 3 do not inhibit axonal regeneration. These data provide a molecular basis to assess the contribution of Nogo to the failure of axonal regeneration in the adult CNS.     

Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors

After lesions in the differentiated central nervous system (CNS) of higher vertebrates, interrupted fibre tracts do not regrow and elongate by more than an initial sprout of approximately 1 mm. Transplantations of pieces of peripheral nerves into various parts of the CNS demonstrate the widespread capability of CNS neurons to regenerate lesioned axons over long distances in a peripheral nerve environment. CNS white matter, cultured oligodendrocytes (the myelin-producing cells of the CNS), and CNS myelin itself, are strong inhibitors of neuron growth in culture, a property associated with defined myelin membrane proteins of relative molecular mass (Mr) 35,000 (NI-35) and 250,000 (NI-250). We have now intracerebrally applied the monoclonal antibody IN-1, which neutralizes the inhibitory effect of both these proteins, to young rats by implanting antibody-producing tumours. In 2-6-week-old rats we made complete transections of the cortico-spinal tract, a major fibre tract of the spinal cord, the axons of which originate in the motor and sensory neocortex. Previous studies have shown a complete absence of cortico-spinal tract regeneration after the first postnatal week in rats, and in adult hamsters and cats. In IN-1-treated rats, massive sprouting occurred at the lesion site, and fine axons and fascicles could be observed up to 7-11 mm caudal to the lesion within 2-3 weeks. In control rats, a similar sprouting reaction occurred, but the maximal distance of elongation rarely exceeded 1 mm. These results demonstrate the capacity for CNS axons to regenerate and elongate within differentiated CNS tissue after the neutralization of myelin-associated neurite growth inhibitors.     

Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor

Numerous inherited retinal degenerations exist in animals and humans, in which photoreceptors inexplicably degenerate and disappear. In RCS rats with inherited retinal dystrophy, the mutant gene is expressed in the retinal pigment epithelial (RPE) cell, and leads to the loss of photoreceptor cells. Photoreceptors can be rescued from degeneration if they are juxtaposed to wild-type RPE cells in experimental chimaeras or by the transplantation of RPE cells from normal rats. In both cases, the rescue effect extends beyond the immediate boundaries of the normal RPE cells, suggesting trophic action of a diffusible factor(s) from the normal RPE cells. We considered that the fibroblast growth factors, aFGF and bFGF, might have such a trophic role as they are found in the retina and RPE cells; bFGF acts as a neurotrophic agent after axonal injury in several regions of the central nervous system, and bFGF induces retinal regeneration from developing RPE cells. Here we report that subretinal injection of bFGF results in extensive rescue of photoreceptors in RCS rats for at least two months after the injection, and that intravitreal injection of bFGF results in even more widespread rescue, across almost the entire retina. The findings demonstrate for the first time that bFGF can act as a survival-promoting neurotrophic factor in a hereditary neuronal degeneration of the central nervous system.     

Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1

The capacity of the adult brain and spinal cord to repair lesions by axonal regeneration or compensatory fibre growth is extremely limited. A monoclonal antibody (IN-1) raised against NI-220/250, a myelin protein that is a potent inhibitor of neurite growth, promoted axonal regeneration and compensatory plasticity following lesions of the central nervous system (CNS) in adult rats. Here we report the cloning of nogo A, the rat complementary DNA encoding NI-220/250. The nogo gene encodes at least three major protein products (Nogo-A, -B and -C). Recombinant Nogo-A is recognized by monoclonal antibody IN-1, and it inhibits neurite outgrowth from dorsal root ganglia and spreading of 3T3 fibroblasts in an IN-1-sensitive manner. Antibodies against Nogo-A stain CNS myelin and oligodendrocytes and allow dorsal root ganglion neurites to grow on CNS myelin and into optic nerve explants. These data show that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.     

帕金森病发生的肠道多巴胺调控机制

多巴胺(Dopamine,DA)是肠-脑轴中关键的神经递质,在中枢及外周均有广泛分布。帕金森症(Parkinson′s disease,PD)发生是由脑DA系统结构与功能退行性丢失所致,而脑DA补充调控的PD诊疗仍为传统主流。新近研究表明,DA及其受体调节肠道运动,PD患者肠神经变性早于中枢神经变性的发生,并伴有肠道DA减少及胃肠神经功能紊乱等非运动症状。本文综述了多巴胺在肠-脑轴的表达、分布、功能及PD发生的肠道多巴胺调控新机制,为基于肠道多巴胺的PD早期诊疗策略提供启示。     

Retinal pigmented epithelial cells induced to transdifferentiate to neurons by laminin

Although the regeneration of nervous tissue in the vertebrate is very limited, there are a few remarkable examples of this process. Understanding the factors that regulate CNS regeneration in those areas of the nervous system where it occurs, will doubtless provide generally applicable, essential information about the process. It has been known for some time that the amphibian retina regenerates following its destruction. Transplant studies, confirmed later by in vitro experiments, have shown that one source of new neurons in regenerating retina is the retinal pigmented epithelium (RPE). RPE cells can transdifferentiate to either neurons or lens cells in culture, but little is known about the factors that regulate this process. A recent study in vivo of retinal regeneration provided evidence that the association of RPE cells with the retinal vascular membrane is an important step in transdifferentiation. We report here that transdifferentiation in vitro is profoundly influenced by the substrate on which the cells are cultured; RPE cells plated on laminin-containing substrates frequently transdifferentiate into neurons. In addition, we have found a high concentration of laminin in the Rana retinal vascular membrane. Therefore, we propose that retinal regeneration is initiated by changes in the composition of the extracellular matrix that RPE cells contact early in the process.     

眼镜蛇毒神经生长因子对成年猫坐骨神经损伤治疗效果的实验室观察

目的 :探讨从眼镜蛇毒分离纯化出的神经生长因子(nervegrowthfactor,NGF)对成年猫坐骨经损伤后的影响。方法 :本实验制成成年猫坐骨神经损伤模型 ,损伤局部注射蛇毒NGF(2μg/kg/d) ,分别治疗10d和30d ,并与对照组(损伤坐骨神经 ,不给药物)比较。结果 :眼镜蛇毒NGF在神经损伤早期应用能减轻神经纤维发生的溃变 ,促进神经纤维再生。结论 :损伤局部长时间注射NGF会导致神经纤维增生过度 ,丧失传导功能     

Schwann cells induce morphological transformation of sensory neurones in vitro

Cell-cell interactions are thought to play a crucial part in determining the developmental fate of vertebrate cells and regulating their subsequent differentiation. In the peripheral nervous system, for example, signals from neuronal axons determine whether or not some Schwann cells wrap their plasma membrane concentricially around the axon to form a myelin sheath. Moreover, there is some evidence that the interactions between Schwann cells and neurones are not all one way: for example, Schwann cells are thought to provide signals for neuronal sprouting and regeneration. However, there are no clear examples in which Schwann cells have been shown to influence the normal development of neurones. Here I have used purified populations of embryonic sensory neurones and Schwann cells to demonstrate that Schwann cells have a dramatic influence on the development of these neurones. In the presence of Schwann cells, but not other cell types, the sensory neurones undergo a morphological transformation from an immature bipolar form to a mature pseudo-unipolar form. This provides a striking example of the importance of glial cells for neuronal development.     

血脑屏障和中枢神经系统疾病相关性的研究进展

中枢神经系统接受全身各处的传入信息,经中枢神经系统整合加工后成为协调的运动传出,或者储存在中枢神经系统内成为学习、记忆的神经基础.中枢神经系统易受到致病因素影响而发生以精神活动障碍为主要表现的疾病,同时亦可出现中枢神经系统退行性病变.而血脑屏障能够使脑组织少受甚至不受循环血液中有害物质的损害,从而保持脑组织内环境的基本稳定,对维持中枢神经系统正常生理状态具有重要的生物学意义.对血脑屏障与中枢神经系统疾病相关性的研究进展进行总结与综述,以期为中枢神经系统疾病的预防与治疗提供更新与更全面的理论基础.