scholarly journals Peripheral axonal ensheathment is regulated by Ral GTPase and the exocyst complex

2019 ◽  
Author(s):  
Joana F. Silva-Rodrigues ◽  
Cátia F. Patrício-Rodrigues ◽  
Vicente de Sousa-Xavier ◽  
Pedro M. Augusto ◽  
Ana C. Fernandes ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nerves ◽  
Growth And Development ◽  
Specific Factor ◽  
Secretory Vesicles ◽  
Neuronal Function ◽  
Exocyst Complex ◽  
Membrane Growth ◽  
Ral Gtpase

AbstractAxon ensheathment is fundamental for fast impulse conduction and the normal physiological functioning of the nervous system. Defects in axonal insulation lead to debilitating conditions, but despite its importance, the molecular players responsible are poorly defined. Here, we identify Ral GTPase as a key player in axon ensheathment in Drosophila larval peripheral nerves. We demonstrate through genetic analysis that Ral action through the exocyst complex is sufficient and necessary in wrapping glial cells to regulate their growth and development. We suggest that the Ral-exocyst pathway controls the targeting of secretory vesicles for membrane growth or for the secretion of a wrapping glia-specific factor that itself regulates growth. In summary, our findings provide a new molecular understanding of the process by which axons are ensheathed in vivo, a process critical for normal neuronal function.

scholarly journals Battery-free, fully implantable optofluidic cuff system for wireless optogenetic and pharmacological neuromodulation of peripheral nerves

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw5296 ◽  
Author(s):  
Yi Zhang ◽  
Aaron D. Mickle ◽  
Philipp Gutruf ◽  
Lisa A. McIlvried ◽  
Hexia Guo ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Peripheral Nerves ◽  
Light Emitting Diode ◽  
Microfluidic System ◽  
Neuronal Function ◽  
Pharmacological Agents ◽  
Light Emitting ◽  
And Function

Studies of the peripheral nervous system rely on controlled manipulation of neuronal function with pharmacologic and/or optogenetic techniques. Traditional hardware for these purposes can cause notable damage to fragile nerve tissues, create irritation at the biotic/abiotic interface, and alter the natural behaviors of animals. Here, we present a wireless, battery-free device that integrates a microscale inorganic light-emitting diode and an ultralow-power microfluidic system with an electrochemical pumping mechanism in a soft platform that can be mounted onto target peripheral nerves for programmed delivery of light and/or pharmacological agents in freely moving animals. Biocompliant designs lead to minimal effects on overall nerve health and function, even with chronic use in vivo. The small size and light weight construction allow for deployment as fully implantable devices in mice. These features create opportunities for studies of the peripheral nervous system outside of the scope of those possible with existing technologies.

scholarly journals Transcriptomic analysis reveals a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles

2022 ◽  
Author(s):  
Emily Robb ◽  
Erin McCammick ◽  
Duncan Wells ◽  
Paul McVeigh ◽  
Erica Gardiner ◽  
...  
Keyword(s):  
Nervous System ◽  
Rapid Growth ◽  
Growth And Development ◽  
Liver Fluke ◽  
Fasciola Hepatica ◽  
Expression Profiles ◽  
Neuronal Signalling ◽  
Growth Development

Fasciola spp. liver fluke have significant impacts in veterinary and human medicine. The absence of a vaccine and increasing anthelmintic resistance threaten sustainable control and underscore the need for novel flukicides. Functional genomic approaches underpinned by in vitro culture of juvenile Fasciola hepatica facilitate control target validation in the most pathogenic life stage. Comparative transcriptomics of in vitro and in vivo maintained 21 day old F. hepatica finds that 86% of genes are expressed at similar levels across maintenance treatments suggesting commonality in core biological functioning within these juveniles. Phenotypic comparisons revealed higher cell proliferation and growth rates in the in vivo juveniles compared to their in vitro counterparts. These phenotypic differences were consistent with the upregulation of neoblast-like stem cell and cell-cycle associated genes in in vivo maintained worms. The more rapid growth/development of in vivo juveniles was further evidenced by a switch in cathepsin protease expression profiles, dominated by cathepsin B in in vitro juveniles and then by cathepsin L in in vivo juveniles. Coincident with more rapid growth/development was the marked downregulation of both classical and peptidergic neuronal signalling components in in vivo maintained juveniles, supporting a role for the nervous system in regulating liver fluke growth and development. Differences in the miRNA complements of in vivo and in vitro juveniles identified 31 differentially expressed miRNAs, notably fhe-let-7a-5p , fhe-mir-124-3p and, miRNAs predicted to target Wnt-signalling, supporting a key role for miRNAs in driving the growth/developmental differences in the in vitro and in vivo maintained juvenile liver fluke. Widespread differences in the expression of neuronal genes in juvenile fluke grown in vitro and in vivo expose significant interplay between neuronal signalling and the rate of growth/development, encouraging consideration of neuronal targets in efforts to dysregulate growth/development for parasite control.

scholarly journals Studies on the Regulatory Roles and Related Mechanisms of lncRNAs in the Nervous System

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zijian Zhou ◽  
Dake Qi ◽  
Quan Gan ◽  
Fang Wang ◽  
Bengang Qin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Growth And Development ◽  
Noncoding Rnas ◽  
Regulatory Function ◽  
Full Understanding ◽  
Cellular Processes ◽  
Physiological Processes

Long noncoding RNAs (lncRNAs) have attracted extensive attention due to their regulatory role in various cellular processes. Emerging studies have indicated that lncRNAs are expressed to varying degrees after the growth and development of the nervous system as well as injury and degeneration, thus affecting various physiological processes of the nervous system. In this review, we have compiled various reported lncRNAs related to the growth and development of central and peripheral nerves and pathophysiology (including advanced nerve centers, spinal cord, and peripheral nervous system) and explained how these lncRNAs play regulatory roles through their interactions with target-coding genes. We believe that a full understanding of the regulatory function of lncRNAs in the nervous system will contribute to understand the molecular mechanism of changes after nerve injury and will contribute to discover new diagnostic markers and therapeutic targets for nerve injury diseases.

scholarly journals Discoidin domain receptor regulates ensheathment, survival, and caliber of peripheral axons

2021 ◽  
Author(s):  
Megan M. Corty ◽  
Alexandria P. Lassetter ◽  
Jo Q. Hill ◽  
Amy E. Sheehan ◽  
F. Javier Bernardo-Garcia ◽  
...  
Keyword(s):  
Peripheral Nerves ◽  
Motor Behavior ◽  
Genetic Interaction ◽  
Neuronal Function ◽  
Term Survival ◽  
Discoidin Domain Receptor ◽  
And Function ◽  
Circuit Function

Invertebrate axons and small caliber axons in mammalian peripheral nerves are unmyelinated but still ensheathed by glia. How this type of ensheathment is controlled and its roles in supporting neuronal function remain unclear. We performed an in vivo RNAi screen in Drosophila to identify glial genes required for axon ensheathment and identified the conserved receptor tyrosine kinase Discoidin domain receptor (Ddr). In larval peripheral nerves, loss of Ddr resulted in incomplete ensheathment of axons. We found a strong dominant genetic interaction between Ddr and the fly type XV/XVIII collagen Multiplexin (Mp), suggesting Ddr functions a collagen receptor to drive wrapping of axons during development. Surprisingly, while ablation of glia that wrap axons severely impaired larval motor behavior, incomplete wrapping in Ddr mutants was sufficient to support basic circuit function. In adult nerves, loss of Ddr from glia decreased long-term survival of sensory neurons and significantly reduced axon caliber without overtly affecting ensheathment. Our data establish a crucial role for non-myelinating glia in peripheral nerve development and function across the lifespan, and identify Ddr as a key regulator of axon-glia interactions during ensheathment.

scholarly journals Current Advances in Comprehending Dynamics of Regenerating Axons and Axon–Glia Interactions after Peripheral Nerve Injury in Zebrafish

2021 ◽  
Vol 22 (5) ◽  
pp. 2484
Author(s):  
David Gonzalez ◽  
Miguel L. Allende
Keyword(s):  
Nervous System ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Time Lapse ◽  
Cell Types ◽  
Regenerative Process ◽  
Time Lapse Microscopy ◽  
Different Cell Types

Following an injury, axons of both the central nervous system (CNS) and peripheral nervous system (PNS) degenerate through a coordinated and genetically conserved mechanism known as Wallerian degeneration (WD). Unlike central axons, severed peripheral axons have a higher capacity to regenerate and reinnervate their original targets, mainly because of the favorable environment that they inhabit and the presence of different cell types. Even though many aspects of regeneration in peripheral nerves have been studied, there is still a lack of understanding regarding the dynamics of axonal degeneration and regeneration, mostly due to the inherent limitations of most animal models. In this scenario, the use of zebrafish (Danio rerio) larvae combined with time-lapse microscopy currently offers a unique experimental opportunity to monitor the dynamics of the regenerative process in the PNS in vivo. This review summarizes the current knowledge and advances made in understanding the dynamics of the regenerative process of PNS axons. By using different tools available in zebrafish such as electroablation of the posterior lateral line nerve (pLLn), and laser-mediated transection of motor and sensory axons followed by time-lapse microscopy, researchers are beginning to unravel the complexity of the spatiotemporal interactions among different cell types during the regenerative process. Thus, understanding the cellular and molecular mechanisms underlying the degeneration and regeneration of peripheral nerves will open new avenues in the treatment of acute nerve trauma or chronic conditions such as neurodegenerative diseases.

scholarly journals “Skittish” Abca2 Knockout Mice Display Tremor, Hyperactivity, and Abnormal Myelin Ultrastructure in the Central Nervous System

2006 ◽  
Vol 27 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Jody T. Mack ◽  
Vladimir Beljanski ◽  
Athena M. Soulika ◽  
Danyelle M. Townsend ◽  
Carol B. Brown ◽  
...  
Keyword(s):  
Nervous System ◽  
Knockout Mice ◽  
Gene Knockout ◽  
Mendelian Inheritance ◽  
Developmental Studies ◽  
Wild Type ◽  
Reduced Body ◽  
Membrane Growth ◽  
The Central Nervous System

ABSTRACT The ATP-binding cassette transporter 2 (ABCA2) is an endolysosomal protein most highly expressed in the central and peripheral nervous system tissues and macrophages. Previous studies indicated its role in cholesterol/steroid (estramustine, estradiol, and progesterone) trafficking/sequestration, oxidative stress response, and Alzheimer's disease. Developmental studies have shown its expression during macrophage and oligodendrocyte differentiation, processes requiring membrane growth. To determine the in vivo function(s) of this transporter, we generated a knockout mouse from a gene-targeted disruption of the murine ABCA2 gene. Knockout males and females are viable and fertile. However, a non-Mendelian inheritance pattern was shown among male progeny of heterozygous crosses. Compared to wild-type and heterozygous littermates, knockout mice displayed a tremor without ataxia, hyperactivity, and reduced body weight; the latter two phenotypes were more marked in females than in males. This sexual disparity suggests a role for ABCA2 in hormone-dependent neurological and/or developmental pathways. Myelin sheath thickness in the spinal cords of knockout mice was greatly increased compared to that in wild-type mice, while a significant reduction in myelin membrane periodicity (compaction) was observed in both spinal cords and cerebra of knockout mice. Loss of ABCA2 function in vivo resulted in abnormal myelin compaction in spinal cord and cerebrum, an ultrastructural defect that we propose to be the cause of the phenotypic tremor.

scholarly journals Peripheral nerve magnetic resonance imaging

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1803 ◽  
Author(s):  
Yongsheng Chen ◽  
E. Mark Haacke ◽  
Jun Li
Keyword(s):  
Magnetic Resonance Imaging ◽  
Nervous System ◽  
Magnetic Resonance ◽  
High Resolution ◽  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Morphological Changes ◽  
Quantitative Mri ◽  
Resonance Imaging

Magnetic resonance imaging (MRI) has been used extensively in revealing pathological changes in the central nervous system. However, to date, MRI is very much underutilized in evaluating the peripheral nervous system (PNS). This underutilization is generally due to two perceived weaknesses in MRI: first, the need for very high resolution to image the small structures within the peripheral nerves to visualize morphological changes; second, the lack of normative data in MRI of the PNS and this makes reliable interpretation of the data difficult. This article reviews current state-of-the-art capabilities in in vivo MRI of human peripheral nerves. It aims to identify areas where progress has been made and those that still require further improvement. In particular, with many new therapies on the horizon, this review addresses how MRI can be used to provide non-invasive and objective biomarkers in the evaluation of peripheral neuropathies. Although a number of techniques are available in diagnosing and tracking pathologies in the PNS, those techniques typically target the distal peripheral nerves, and distal nerves may be completely degenerated during the patient’s first clinic visit. These techniques may also not be able to access the proximal nerves deeply embedded in the tissue. Peripheral nerve MRI would be an alternative to circumvent these problems. In order to address the pressing clinical needs, this review closes with a clinical protocol at 3T that will allow high-resolution, high-contrast, quantitative MRI of the proximal peripheral nerves.

scholarly journals Microbiomics in Collusion with the Nervous System in Carcinogenesis: Diagnosis, Pathogenesis and Treatment

2021 ◽  
Vol 9 (10) ◽  
pp. 2129
Author(s):  
Rodney Hull ◽  
Georgios Lolas ◽  
Stylianos Makrogkikas ◽  
Lasse D. Jensen ◽  
Konstantinos N. Syrigos ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nerves ◽  
Growth And Development ◽  
Nervous Tissue ◽  
Cancer Growth ◽  
Vagus Nerves ◽  
Hallmarks Of Cancer ◽  
Naturally Occurring ◽  
Recent Interest ◽  
Stimulation Of

The influence of the naturally occurring population of microbes on various human diseases has been a topic of much recent interest. Not surprisingly, continuously growing attention is devoted to the existence of a gut brain axis, where the microbiota present in the gut can affect the nervous system through the release of metabolites, stimulation of the immune system, changing the permeability of the blood–brain barrier or activating the vagus nerves. Many of the methods that stimulate the nervous system can also lead to the development of cancer by manipulating pathways associated with the hallmarks of cancer. Moreover, neurogenesis or the creation of new nervous tissue, is associated with the development and progression of cancer in a similar manner as the blood and lymphatic systems. Finally, microbes can secrete neurotransmitters, which can stimulate cancer growth and development. In this review we discuss the latest evidence that support the importance of microbiota and peripheral nerves in cancer development and dissemination.

Monitoring stem cell migration in the nervous system by in vivo magnetic resonance imaging

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S692-S692
Author(s):  
Mathias Hoehn ◽  
Uwe Himmelreich ◽  
Ralph Weber ◽  
Pedro Ramos-Cabrer ◽  
Susanne Wegener ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Nervous System ◽  
Stem Cell ◽  
Cell Migration ◽  
Magnetic Resonance ◽  
Resonance Imaging ◽  
Stem Cell Migration
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