Advances of tooth‐derived stem cells in neural diseases treatments and nerve tissue regeneration

Nerous system diseases, both central and peripheral, bring an incredible burden onto patients and enormously reduce their quality of life. Currently, there are still no effective treatments to repair nerve lesions that do not have side effects. Stem cell–based therapies, especially those using dental stem cells, bring new hope to neural diseases. Dental stem cells, derived from the neural crest, have many characteristics that are similar to neural cells, indicating that they can be an ideal source of cells for neural regeneration and repair. This review summarizes the neural traits of all the dental cell types, including DPSCs, PDLCs, DFCs, APSCs and their potential applications in nervous system diseases. We have summed up the advantages of dental stem cells in neural repair, such as their neurotrophic and neuroprotective traits, easy harvest and low rejective reaction rate, among others. Taken together, dental stem cells are an ideal cell source for neural tissue regeneration and repair.     

Optogenetic manipulation of neural circuitry in vivo

Recent advances in optogenetics have permitted investigations of specific cell types in the nervous system with unprecedented precision and control. This review will discuss the use of optogenetic techniques in the study of mammalian neural circuitry in vivo, as well as practical and theoretical considerations in their application.     

Optogenetic Control of Targeted Peripheral Axons in Freely Moving Animals

Optogenetic control of the peripheral nervous system (PNS) would enable novel studies of motor control, somatosensory transduction, and pain processing. Such control requires the development of methods to deliver opsins and light to targeted sub-populations of neurons within peripheral nerves. We report here methods to deliver opsins and light to targeted peripheral neurons and robust optogenetic modulation of motor neuron activity in freely moving, non-transgenic mammals. We show that intramuscular injection of adeno-associated virus serotype 6 enables expression of channelrhodopsin (ChR2) in motor neurons innervating the injected muscle. Illumination of nerves containing mixed populations of axons from these targeted neurons and from neurons innervating other muscles produces ChR2-mediated optogenetic activation restricted to the injected muscle. We demonstrate that an implanted optical nerve cuff is well-tolerated, delivers light to the sciatic nerve, and optically stimulates muscle in freely moving rats. These methods can be broadly applied to study PNS disorders and lay the groundwork for future therapeutic application of optogenetics.     

Endothelin-1 as a neuropeptide: neurotransmitter or neurovascular effects?

Endothelin-1 (ET-1) is an endothelium-derived peptide that also possesses potent mitogenic activity. There is also a suggestion the ET-1 is a neuropeptide, based mainly on its histological identification in both the central and peripheral nervous system in a number of species, including man. A neuropeptide role for ET-1 is supported by studies showing a variety of effects caused following its administration into different regions of the brain and by application to peripheral nerves. In addition there are studies proposing that ET-1 is implicated in a number of neural circuits where its transmitter affects range from a role in pain and temperature control to its action on the hypothalamo-neurosecretory system. While the effect of ET-1 on nerve tissue is beyond doubt, its action on nerve blood flow is often ignored. Here, we review data generated in a number of species and using a variety of experimental models. Studies range from those showing the distribution of ET-1 and its receptors in nerve tissue to those describing numerous neurally-mediated effects of ET-1.     

Distribution and function of voltage-gated sodium channels in the nervous system

Voltage-gated sodium channels (VGSCs) are the basic ion channels for neuronal excitability, which are crucial for the resting potential and the generation and propagation of action potentials in neurons. To date, at least nine distinct sodium channel isoforms have been detected in the nervous system. Recent studies have identified that voltage-gated sodium channels not only play an essential role in the normal electrophysiological activities of neurons but also have a close relationship with neurological diseases. In this study, the latest research findings regarding the structure, type, distribution, and function of VGSCs in the nervous system and their relationship to neurological diseases, such as epilepsy, neuropathic pain, brain tumors, neural trauma, and multiple sclerosis, are reviewed in detail.     

光敏感通道(Channelrhodopsin-2)——神经回路功能和神经系统疾病研究的新工具

光敏感通道(channelrhodopsin-2,ChR2)是一种受光脉冲控制的具有7次跨膜结构的非选择性阳离子通道蛋白,自1991年从莱茵衣藻中发现后被许多实验室所关注.依据ChR2可以快速形成光电流,使细胞发生去极化反应的电生理特性,ChR2已被广泛应用于神经系统的研究.与传统的神经系统研究方法如电生理技术、神经药理学方法相比,用光脉冲控制带有ChR2的神经元的活动,具有更高的空间选择性和特异性.ChR2作为光基因技术的核心组成部分,对神经科学是一个崭新的应用前景广泛的研究工具.近年来ChR2不仅应用于视觉、躯体感觉、听觉和嗅觉等多条感觉神经回路的形态和功能研究,还被应用于各种临床神经系统疾病的研究.本文总结了目前ChR2在神经系统中的研究进展,并对ChR2未来的应用前景作了进一步展望.     

Optogenetic investigation of neural circuits in vivo

The recent development of light-activated optogenetic probes allows for the identification and manipulation of specific neural populations and their connections in awake animals with unprecedented spatial and temporal precision. This review describes the use of optogenetic tools to investigate neurons and neural circuits in vivo. We describe the current panel of optogenetic probes, methods of targeting these probes to specific cell types in the nervous system, and strategies of photostimulating cells in awake, behaving animals. Finally, we survey the application of optogenetic tools to studying functional neuroanatomy, behavior and the etiology and treatment of various neurological disorders.     

上转换纳米颗粒介导的无线光遗传学技术的研究进展

光遗传学技术是结合基因工程和光学技术对生物体特定细胞进行精确调控的新兴生物技术,该技术可以特异性地兴奋或抑制靶神经元,成为解析介导特定行为神经环路的强有力的工具.传统技术依赖光纤,对脑组织有损伤且限制了动物的自由活动.新一代上转换纳米颗粒介导的无线光遗传学技术,借助近红外光组织穿透相对深的特性,能够对啮齿类动物脑组织深层核团进行无线调控,克服了传统技术中埋置光纤存在的缺陷.本文总结了上转换纳米颗粒介导的无线光遗传学技术的发展历程及现状,比较分析了这类无线光遗传学技术的优缺点,最后对该技术面临的挑战及未来前景进行了分析和展望.     

Dual Color Neural Activation and Behavior Control with Chrimson and CoChR in Caenorhabditis elegans

By enabling a tight control of cell excitation, optogenetics is a powerful approach to study the function of neurons and neural circuits. With its transparent body, a fully mapped nervous system, easily quantifiable behaviors and many available genetic tools, Caenorhabditis elegans is an extremely well-suited model to decipher the functioning logic of the nervous system with optogenetics. Our goal was to establish an efficient dual color optogenetic system for the independent excitation of different neurons in C. elegans. We combined two recently discovered channelrhodopsins: the red-light sensitive Chrimson from Chlamydomonas noctigama and the blue-light sensitive CoChR from Chloromonas oogama. Codon-optimized versions of Chrimson and CoChR were designed for C. elegans and expressed in different mechanosensory neurons. Freely moving animals produced robust behavioral responses to light stimuli of specific wavelengths. Since CoChR was five times more sensitive to blue light than the commonly used ChR2, we were able to use low blue light intensities producing no cross-activation of Chrimson. Thanks to these optogenetics tools, we revealed asymmetric cross-habituation effects between the gentle and harsh touch sensory motor pathways. Collectively, our results establish the Chrimson/CoChR pair as a potent tool for bimodal neural excitation in C. elegans and equip this genetic model organism for the next generation of in vivo optogenetic analyses.     

长链非编码RNA在神经系统发育及神经性疾病中的作用

长链非编码RNA(long non-coding RNA,lncRNA)是一类转录本长度在200至数千个核苷酸序列,且不具有蛋白质编码潜能的非编码RNA。相较于研究较多的微小RNA（microRNA,miRNA）和干扰小RNA（small interfering,siRNA）等非编码小RNA,lncRNA的许多功能仍尚不清楚。但越来越多的研究发现,lncRNA可通过多种方式调控中枢神经系统发育,包括表观遗传组蛋白甲基化、转录辅因子调控、可变剪接调控等途经。而以上途经的异常均与多种人类重大疾病的发生密切相关,例如,阿尔兹海默症（Alzheimer’s disease,AD）、自闭症（autism spectrum disorder,ASD）、精神分裂症（schizophrenia,SZ）等。本文就lncRNA在表观遗传水平、转录水平、转录后水平和翻译水平上调控神经系统发育以及其在人类神经性疾病中的作用进行综述。     

Optogenetic manipulation of neural activity in C. elegans: From synapse to circuits and behaviour

The emerging field of optogenetics allows for optical activation or inhibition of excitable cells. In 2005, optogenetic proteins were expressed in the nematode Caenorhabditis elegans for the first time. Since then, C. elegans has served as a powerful platform upon which to conduct optogenetic investigations of synaptic function, circuit dynamics and the neuronal basis of behaviour. The C. elegans nervous system, consisting of 302 neurons, whose connectivity and morphology has been mapped completely, drives a rich repertoire of behaviours that are quantifiable by video microscopy. This model organism's compact nervous system, quantifiable behaviour, genetic tractability and optical accessibility make it especially amenable to optogenetic interrogation. Channelrhodopsin‐2 (ChR2), halorhodopsin (NpHR/Halo) and other common optogenetic proteins have all been expressed in C. elegans. Moreover, recent advances leveraging molecular genetics and patterned light illumination have now made it possible to target photoactivation and inhibition to single cells and to do so in worms as they behave freely. Here, we describe techniques and methods for optogenetic manipulation in C. elegans. We review recent work using optogenetics and C. elegans for neuroscience investigations at the level of synapses, circuits and behaviour.     

Preliminary study on nerve regeneration through an autologous venous tube

Large posttraumatic defects in the peripheral nervous system bring up serious problems to the surgeon. There is no definitive answer yet. The authors present a model for nervous regeneration studies; venous autograft was used to bridge defects in a divided rat sciatic nerve; the venous tube guided the regenerating axons towards the distal stump over up to 1.9 cm length. Preliminary studies about nervous regeneration stimulation with autologous Schwann cells are discussed.     

Dissecting planarian central nervous system regeneration by the expression of neural-specific genes

The planarian central nervous system (CNS) can be used as a model for studying neural regeneration in higher organisms. Despite its simple structure, recent studies have shown that the planarian CNS can be divided into several molecular and functional domains defined by the expression of different neural genes. Remarkably, a whole animal, including the molecularly complex CNS, can regenerate from a small piece of the planarian body. In this study, a collection of neural markers has been used to characterize at the molecular level how the planarian CNS is rebuilt. Planarian CNS is composed of an anterior brain and a pair of ventral nerve cords that are distinct and overlapping structures in the head region. During regeneration, 12 neural markers have been classified as early, mid-regeneration and late expression genes depending on when they are upregulated in the regenerative blastema. Interestingly, the results from this study show that the comparison of the expression patterns of different neural genes supports the view that at day one of regeneration, the new brain appears within the blastema, whereas the pre-existing ventral nerve cords remain in the old tissues. Three stages in planarian CNS regeneration are suggested.     

Integrins and the extracellular matrix: key mediators of development and regeneration of the sensory nervous system

The somatosensory nervous system is responsible for the transmission of a multitude of sensory information from specialized receptors in the periphery to the central nervous system. Sensory afferents can potentially be damaged at several sites: in the peripheral nerve; the dorsal root; or the dorsal columns of the spinal cord; and the success of regeneration depends on the site of injury. The regeneration of peripheral nerve branches following injury is relatively successful compared to central branches. This is largely attributed to the presence of neurotrophic factors and a Schwann cell basement membrane rich in permissive extracellular matrix (ECM) components which promote axonal regeneration in the peripheral nerve. Modulation of the ECM environment and/or neuronal integrins may enhance regenerative potential of sensory neurons following peripheral or central nerve injury or disease. This review describes the interactions between integrins and ECM molecules (particularly the growth supportive ligands, laminin, and fibronectin; and the growth inhibitory chondroitin sulfate proteoglycans (CSPGs)) during development and regeneration of sensory neurons following physical injury or neuropathy.     

神经干细胞迁移的研究进展

神经干细胞的定向迁移是胚胎神经系统发育的先决条件,同时在成体组织的许多生理、病理过程中也起着重要作用;研究发现,许多神经退行性疾病都与神经干细胞迁移的缺陷相关。近年来,越来越多的证据表明,无论是内源性的还是移植的神经干细胞都有向大脑损伤部位迁移的特性,显示出神经干细胞用于神经再生及损伤修复治疗的潜能。该文着重在神经干细胞的基本特性以及神经干细胞定向迁移的细胞与分子机制研究等方面进行了综述。     

Differential expression of the Tmem132 family genes in the developing mouse nervous system

The family of novel transmembrane proteins (TMEM) 132 have been associated with multiple neurological disorders and cancers in humans, but have hardly been studied in vivo. Here we report the expression patterns of the five Tmem132 genes (a, b, c, d and e) in developing mouse nervous system with RNA in situ hybridization in wholemount embryos and tissue sections. Our results reveal differential and partially overlapping expression of multiple Tmem132 family members in both the central and peripheral nervous system, suggesting potential partial redundancy among them.     

The role of nervous system in adaptive response of bone to mechanical loading

Bone tissue is remodeled through the catabolic function of the osteoclasts and the anabolic function of the osteoblasts. The process of bone homeostasis and metabolism has been identified to be co-ordinated with several local and systemic factors, of which mechanical stimulation acts as an important regulator. Very recent studies have shown a mutual effect between bone and other organs, which means bone influences the activity of other organs and is also influenced by other organs and systems of the body, especially the nervous system. With the discovery of neuropeptide (calcitonin gene-related peptide, vasoactive intestinal peptide, substance P, and neuropeptide Y) and neurotransmitter in bone and the adrenergic receptor observed in osteoclasts and osteoblasts, the function of peripheral nervous system including sympathetic and sensor nerves in bone resorption and its reaction to on osteoclasts and osteoblasts under mechanical stimulus cannot be ignored. Taken together, bone tissue is not only the mechanical transmitter, but as well the receptor of neural system under mechanical loading. This review aims to summarize the relationship among bone, nervous system, and mechanotransduction.     

电刺激联合干细胞修复周围神经损伤的研究进展

周围神经损伤在创伤中较为常见,易造成神经系统部分或全部损伤,从而导致功能丧失和其他神经性疾病．尽管周围神经损伤的治疗效果随着科技的发展有了明显提高,但距离真正的形态和功能重建还相差甚远,神经再生及功能恢复速度缓慢仍是临床治疗的难点．电刺激因使用方便、无创和副作用小等优点越来越受到研究者的青睐,与干细胞联合广泛用于周围神经损伤修复的体外研究．本文论述了电刺激联合干细胞在周围神经损伤修复方面的研究进展,并讨论了其可能的作用机理．特别分析了电刺激联合干细胞在周围神经损伤修复研究中的难点,展望了其发展前景．     

研究报告：缓激肽上调豚鼠肠道黏膜下神经丛环氧合酶2的表达

目的缓激肽和缓激肽B2受体在肠神经系统中起重要作用。缓激肽通常参与肠道的炎症反应和神经保护,这种作用取决于缓激肽诱导前列腺素的形成。环氧合酶1 (COX1)和环氧合酶2 (COX2)催化花生四烯酸转化为前列腺素。本研究旨在探讨缓激肽刺激对豚鼠肠神经前列腺素E2 (p GE2)释放和COX2表达的影响及信号机制。方法本文通过免疫荧光检测肠神经细胞中COX2与神经细胞标志物Anti-Hu和ch AT的表达;采用PCR及蛋白质印迹(Western blot)检测不同条件下缓激肽刺激对COX2表达的影响;使用缓激肽B1受体的选择性拮抗剂Leu-8和B2受体的选择性拮抗剂HOE-140,研究缓激肽影响COX2表达的信号机制;利用COX2选择性拮抗剂NS398和COX1拮抗剂FR12207,观察COX2在缓激肽诱导p EG2释放的作用。结果 COX2与神经细胞标志物Anti-Hu和ch AT在肠神经细胞上共同表达,缓激肽可通过B2受体诱导肠神经细胞COX2的表达。缓激肽刺激引起的肠神经细胞p GE2的释放与COX2表达升高密切相关。结论缓激肽通过B2R影响肠道黏膜下神经丛COX2的表达,肠道缓激肽...