Local modulation of plus-end transport targets herpesvirus entry and egress in sensory axons

The core structures of many viruses move within cells by association with host cytoskeletal motor proteins; however, the mechanisms by which intracellular viral particles are transported toward sites of replication or the cell periphery at distinct stages of infection remain to be understood. The regulation of herpesvirus directional transport in sensory neurons was examined by tracking individual viral capsids within axons at multiple frames per s. After entry into axons, capsids underwent bidirectional and saltatory movement to the cell body independently of endosomes. A comparison of entry transport to a previous analysis of capsid axonal transport during egress revealed that capsid targeting in and out of cells occurs by modulation of plus-end, but not minus-end, motion. Entry transport was unperturbed by the presence of egressing virus from a prior infection, indicating that transport direction is not modulated globally by viral gene expression, but rather directly by a component of the viral particle.     

糖尿病大鼠胃窦胆碱能神经元与胃动力障碍的关系

目的 探讨链脲佐菌素(STZ)-糖尿病大鼠胃动力障碍和胃肌间神经丛胆碱能之间的关系.方法 45只SD大鼠随机分为对照组、糖尿病组和胰岛素组.成模后16 w测定大鼠胃动力,观察胃肌间神经丛胆碱能神经元的形态变化.结果 与对照组比较,糖尿病组大鼠胃动力减弱(P<0.01),胃窦肌间神经丛胆碱能神经元计数显著降低(P<0.01).与糖尿病组相比较,胰岛素组胃动力显著增高 (P<0.05),胃窦肌间神经丛胆碱能神经元平均光密度显著增高(P<0.05),胆碱能神经元计数有改善的趋势(P>0.05).结论 STZ-糖尿病大鼠胃动力障碍可能与胃肌间神经丛胆碱能神经损伤有关,胰岛素治疗能在一定程度上改善糖尿病胃动力障碍.     

Different innervation mechanisms between the lesser and greater curvature of guinea pig antrum

Transmural stimulation (TS) produced a frequency-dependent contraction of the longitudinal muscles from the lesser curvature of the guinea pig antrum, which was abolished by atropine. On the other hand, a response to TS of the strips from the greater curvature was biphasic: a rapid contraction followed by a relaxation, which was abolished by tetrodotoxin. By pretreatment with atropine, rapid contraction of the biphasic response evoked by TS in the greater curvature was abolished and relaxation was augmented. Relaxation to TS of the greater curvature was not affected by prazocine, yohimbine, phentolamine, propranolol, theophylline, apamin, -chymotrypsin, and vasoactive intestinal polypeptide receptor antagonist. Different innervation mechanisms were suggested to be present in the longitudinal muscles between the lesser curvature (innervated with excitatory cholinergic neurons) and the greater cuvature (innervated with excitatory cholinergic neurons and nonadrenergic inhibitory neurons) of the guinea pig antrum.     

Rapid increase in clusters of synaptophysin at onset of homosynaptic potentiation in Aplysia

Imaging studies have shown that even the earliest phases of long-term plasticity are accompanied by the rapid recruitment of synaptic components, which generally requires actin polymerization and may be one of the first steps in a program that can lead to the formation of new stable synapses during late-phase plasticity. However, most of those results come from studies of long-term potentiation in rodent hippocampus and might not generalize to other forms of synaptic plasticity or plasticity in other brain areas and species. For example, recruitment of presynaptic proteins during long-term facilitation by 5HT in Aplysia is delayed for several hours, suggesting that whereas activity-dependent forms of plasticity, such as long-term potentiation, involve rapid recruitment of presynaptic proteins, neuromodulatory forms of plasticity, such as facilitation by 5HT, involve more delayed recruitment. To begin to explore this hypothesis, we examined an activity-dependent form of plasticity, homosynaptic potentiation produced by tetanic stimulation of the presynaptic neuron in Aplysia. We found that homosynaptic potentiation involves presynaptic but not postsynaptic actin and a rapid (under 10 min) increase in the number of clusters of the presynaptic vesicle-associated protein synaptophysin. These results indicate that rapid recruitment of synaptic components is not limited to hippocampal potentiation and support the hypothesis that activity-dependent types of plasticity involve rapid recruitment of presynaptic proteins, whereas neuromodulatory types of plasticity involve more delayed recruitment.     

Adhesion and Growth of Neuralized Mouse Embryonic Stem Cells on Parylene-C/SiO2 Substrates

Neuronal patterning on microfabricated architectures has developed rapidly over the past few years, together with the emergence of soft biocompatible materials and tissue engineering scaffolds. Previously, we introduced a patterning technique based on serum and the biopolymer parylene-C, achieving highly compliant growth of primary neurons and astrocytes on different geometries. Here, we expanded this technique and illustrated that neuralized cells derived from mouse embryonic stem cells (mESCs) followed stripes of variable widths with conformity equal to or higher than that of primary neurons and astrocytes. Our results indicate the presence of undifferentiated mESCs, which also conformed to the underlying patterns to a high degree. This is an exciting and unexpected outcome, as molecular mechanisms governing cell and ECM protein interactions are different in stem cells and primary cells. Our study enables further investigations into the development and electrophysiology of differentiating patterned neural stem cells.     

Acute corticosterone treatment is sufficient to induce anxiety and amygdaloid dendritic hypertrophy

Stress is known to induce dendritic hypertrophy in the basolateral amygdala (BLA) and to enhance anxiety. Stress also leads to secretion of glucocorticoids (GC), and the BLA has a high concentration of glucocorticoid receptors. This raises the possibility that stress-induced elevation in GC secretion might directly affect amygdaloid neurons. To address the possible effects of GC on neurons of amygdala and on anxiety, we used rats treated either acutely with a single dose or chronically with 10 daily doses of high physiological levels of corticosterone (the rat-specific glucocorticoid). Behavior and morphological changes in neurons of BLA were measured 12 days after the initiation of treatment in both groups. A single acute dose of corticosterone was sufficient to induce dendritic hypertrophy in the BLA and heightened anxiety, as measured on an elevated plus maze. Moreover, this form of dendritic hypertrophy after acute treatment was of a magnitude similar to that caused by chronic treatment. Thus, plasticity of BLA neurons is sufficiently sensitive so as to be saturated by a single day of stress. The effects of corticosterone were specific to anxiety, as neither acute nor chronic treatment caused any change in conditioned fear or in general locomotor activity in these animals.     

线粒体释放的凋亡因子与缺血性神经元凋亡

凋亡是细胞接受各种凋亡信号,在基因调控下发生的主动死亡过程。线粒体在脑缺血神经元凋亡的发生过程中起着关键作用。文章就线粒体释放的凋亡相关因子及其在缺血神经元凋亡通路中的作用机制作了综述。     

成年大鼠神经元和星形胶质细胞细胞周期蛋白依赖激酶的表达

目的 研究成年大鼠细胞周期蛋白依赖激酶（CDK）在神经元和星型胶质细胞的表达.方法 应用免疫荧光和激光扫描共聚焦显微镜观察成年大鼠生理状态下大脑皮层或海马CA1区神经元和星型胶质细胞CDK1、CDK2、CDK4的表达.结果 成年大鼠大脑皮层和海马CA1区神经元的细胞核和细胞浆均有CDK1、CDK2和CDK4表达,以胞核为主;星形胶质细胞也有CDK1、CDK2和CDK4的表达,但表达细胞数目较少,且表达这些指标的星形胶质细胞多聚集在海马CA1区.结论 成年大鼠大脑皮层和海马区的神经元和星形胶质细胞均表达CDK,而神经元的CDK表达较星形胶质细胞更为普遍.     

Intrinsic Cardiac Neurons

Intrinsic Cardiac Neurons. Physiological evidence indicates that afferent neurons, local circuit neurons, as well as efferent sympathetic and efferent parasympathetic neurons, are located in the mammalian intrinsic cardiac nervous system. Complex interneuronal interactions can occur between these neurons, as well as between such neurons and other intrathoracic and central nervous system neurons. A variety of neurochemicals have been proposed to be involved in such interneuronal interactions. Thus the electrophysiologic properties and synaptology of intrinsic cardiac neurons may be more varied than has been appreciated accounting, at least in part, for the variety of neuronal responses that in situ intrinsic cardiac neurons are capable of displaying. The various interactions that occur between intrinsic cardiac neurons and other intrathoracic neurons, as well as between neurons in all intrathoracic ganglia and the central nervous system, will have to be characterized in order to clarify the role of the autonomic nervous system regulating the heart throughout each cardiac cycle.     

精氨酸加压素对实验性神经细胞M受体位点数影响的研究

目的 观察精氨酸加压素(AVP)对实验性神经细胞M受体位点数的影响。方法 采用小鼠神经母细胞瘤细胞(NBA_2)无血清培养建立神经细胞老比实验研究模型。以M受体放射性配基分析术研究AVP对实验性神经细胞的M受体位点数的影响。结果 两种不同浓度的AVP皆可使M受体位点数下降(P<0.01),以高浓度组更著。结论 结合以前研究结果,提示AVP使M受体位点数下降的作用可能是其延缓实验性神经细胞老化的机制之一。     

Stimulation of neural regeneration in the mouse retina

Müller glia can serve as a source of new neurons after retinal damage in both fish and birds. Investigations of regeneration in the mammalian retina in vitro have provided some evidence that Müller glia can proliferate after retinal damage and generate new rods; however, the evidence that this occurs in vivo is not conclusive. We have investigated whether Müller glia have the potential to generate neurons in the mouse retina in vivo by eliminating ganglion and amacrine cells with intraocular NMDA injections and stimulating Müller glial to re-enter the mitotic cycle by treatment with specific growth factors. The proliferating Müller glia dedifferentiate and a subset of these cells differentiated into amacrine cells, as defined by the expression of amacrine cell-specific markers Calretinin, NeuN, Prox1, and GAD67-GFP. These results show for the first time that the mammalian retina has the potential to regenerate inner retinal neurons in vivo.     

Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice

Dominant mutations in ubiquitously expressed superoxide dismutase (SOD1) cause familial ALS by provoking premature death of adult motor neurons. To test whether mutant damage to cell types beyond motor neurons is required for the onset of motor neuron disease, we generated chimeric mice in which all motor neurons and oligodendrocytes expressed mutant SOD1 at a level sufficient to cause fatal, early-onset motor neuron disease when expressed ubiquitously, but did so in a cellular environment containing variable numbers of non-mutant, non-motor neurons. Despite high-level mutant expression within 100% of motor neurons and oligodendrocytes, in most of these chimeras, the presence of WT non-motor neurons substantially delayed onset of motor neuron degeneration, increasing disease-free life by 50%. Disease onset is therefore non-cell autonomous, and mutant SOD1 damage within cell types other than motor neurons and oligodendrocytes is a central contributor to initiation of motor neuron degeneration.     

腓骨肌萎缩症的临床与病理

目的：探讨腓骨肌萎缩症(CMT)的临床与病理特点。方法：综合分析20例腓骨肌萎缩症患者的临床资料,神经电生理改变及神经肌肉活检的病理特点。结果：腓骨肌萎缩症的1、2型在临床表现上基本相同,但神经电生理改变及神经肌肉活检的病理特点明显不同。16例CMT1型（肥大型或脱骨鞘型）表现为神经传导速度减慢和脱髓鞘,4例CMT2型（轴索型）表现为神经传导速度正常和轴索变性。结论：神经电生理检查和神经肌肉活检对腓骨肌萎缩症诊断和分型有重要的意义。     

Foundational model of structural connectivity in the nervous system with a schema for wiring diagrams, connectome, and basic plan architecture

The nervous system is a biological computer integrating the body's reflex and voluntary environmental interactions (behavior) with a relatively constant internal state (homeostasis)-- promoting survival of the individual and species. The wiring diagram of the nervous system's structural connectivity provides an obligatory foundational model for understanding functional localization at molecular, cellular, systems, and behavioral organization levels. This paper provides a high-level, downwardly extendible, conceptual framework--like a compass and map--for describing and exploring in neuroinformatics systems (such as our Brain Architecture Knowledge Management System) the structural architecture of the nervous system's basic wiring diagram. For this, the Foundational Model of Connectivity's universe of discourse is the structural architecture of nervous system connectivity in all animals at all resolutions, and the model includes two key elements--a set of basic principles and an internally consistent set of concepts (defined vocabulary of standard terms)--arranged in an explicitly defined schema (set of relationships between concepts) allowing automatic inferences. In addition, rules and procedures for creating and modifying the foundational model are considered. Controlled vocabularies with broad community support typically are managed by standing committees of experts that create and refine boundary conditions, and a set of rules that are available on the Web.     

老年大鼠下丘脑生长抑素神经元的变化

本实验以PAP免疫组织化学方法观察了老年雄性大鼠下丘脑生长抑素(SRIF)神经元系统的变化,结果表明老年大鼠室周核(PV)SRIF神经元群中,除视前室周核(Pep)内阳性细胞减少外,其余部位的阳性细胞增加(P<0.05),并且正中隆起(ME)处染色增强。此外,在内侧视前区(MPO)和弓状核(ARN)的阳性纤维减少,视交叉上核(SCN)内阳性细胞和纤维均减少,而在腹内侧核背内侧区(VMNdm)阳性纤维明显增加。本实验结果提供了下丘脑SRIF神经元老年时期发生不均一性变化的形态学证据。     

Effects of familial hemiplegic migraine type 1 mutations on neuronal P/Q-type Ca2+ channel activity and inhibitory synaptic transmission

Inhibitory synapses play key roles in the modulatory circuitry that regulates pain signaling and generation of migraine headache. A rare, dominant form of this common disease, familial hemiplegic migraine type 1 (FHM1), arises from missense mutations in the pore-forming alpha1A subunit of P/Q-type Ca2+ channels. These channels are normally vital for presynaptic Ca2+ entry and neurotransmitter release at many central synapses, raising questions about effects of FHM1 mutations on neuronal Ca2+ influx and inhibitory and excitatory neurotransmission. We have expressed the four original FHM1 mutant channels in hippocampal neurons from alpha1A knockout mice. Whole-cell recordings indicated that FHM1 mutant channels were less effective than wild-type channels in their ability to conduct P/Q-type current, but not generally different from wild type in voltage-dependent channel gating. Ca2+ influx triggered by action potential waveforms was also diminished. In keeping with decreased channel activity, FHM1 mutant channels were correspondingly impaired in supporting the P/Q-type component of inhibitory neurotransmission. When expressed in wild-type inhibitory neurons, FHM1 mutant channels reduced the contribution of P/Q-type channels to GABAergic synaptic currents, consistent with a competition of mutant and endogenous channels for P/Q-specific slots. In all cases, N-type channels took up the burden of supporting transmission and homeostatic mechanisms maintained overall synaptic strength. The shift to reliance on N-type channels greatly increased the susceptibility to G protein-coupled modulation of neurotransmission, studied with the GABAB agonist baclofen. Thus, mutant-expressing synapses might be weakened in a heightened state of neuromodulation like that provoked by triggers of migraine such as stress.     

Beagle犬含药脑脊液干预皮层神经元出血损伤细胞凋亡时间窗的实验研究

目的探讨中药复方DSQ-03对Beag1e犬含药脑脊液体外培养的皮层神经元凝血酶合并缺血缺氧损伤的保护作用,并探讨其作用的时间窗,为进一步开展临床研究提供依据;方法采用脑脊液药理学和原代神经细胞培养的方法,用Beagle犬的含DSQ-03脑脊液体外培养SD大鼠大脑皮质的神经细胞.用凝血酶合并缺血缺氧(TIH)损伤神经细胞,建立急性脑出血(AICH)的体外细胞模型.在TIH损伤后6 h、12 h、24 h、72h,用流式细胞仪检测细胞凋亡率.结果 AICH细胞模型复制后,神经细胞凋亡在0 h～72 h都有动态变化;Beagle犬含药脑脊液干预ICH的细胞凋亡时间窗:0 h～24 h是最佳干预时机,0 h～72h内仍有意义.结论 DSQ-03含药脑脊液可抑制神经细胞凋亡,其最佳时间窗为0 h～24 h.