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Sample records for nervous system myelin

  1. Review: Glial lineages and myelination in the central nervous system

    PubMed Central

    COMPSTON, ALASTAIR; ZAJICEK, JOHN; SUSSMAN, JON; WEBB, ANNA; HALL, GILLIAN; MUIR, DAVID; SHAW, CHRISTOPHER; WOOD, ANDREW; SCOLDING, NEIL

    1997-01-01

    Oligodendrocytes, derived from stem cell precursors which arise in subventricular zones of the developing central nervous system, have as their specialist role the synthesis and maintenance of myelin. Astrocytes contribute to the cellular architecture of the central nervous system and act as a source of growth factors and cytokines; microglia are bone-marrow derived macrophages which function as primary immunocompetent cells in the central nervous system. Myelination depends on the establishment of stable relationships between each differentiated oligodendrocyte and short segments of several neighbouring axons. There is growing evidence, especially from studies of glial cell implantation, that oligodendrocyte precursors persist in the adult nervous system and provide a limited capacity for the restoration of structure and function in myelinated pathways damaged by injury or disease. PMID:9061442

  2. Evolution of a neuroprotective function of central nervous system myelin.

    PubMed

    Yin, Xinghua; Baek, Rena C; Kirschner, Daniel A; Peterson, Alan; Fujii, Yasuhisa; Nave, Klaus-Armin; Macklin, Wendy B; Trapp, Bruce D

    2006-01-30

    The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when a tetraspan membrane protein, myelin proteolipid protein (PLP), replaced the type I integral membrane protein, P0, as the major protein of myelin. To investigate possible reasons for this molecular switch, we genetically engineered mice to express P0 instead of PLP in CNS myelin. In the absence of PLP, the ancestral P0 provided a periodicity to mouse compact CNS myelin that was identical to mouse PNS myelin, where P0 is the major structural protein today. The PLP-P0 shift resulted in reduced myelin internode length, degeneration of myelinated axons, severe neurological disability, and a 50% reduction in lifespan. Mice with equal amounts of P0 and PLP in CNS myelin had a normal lifespan and no axonal degeneration. These data support the hypothesis that the P0-PLP shift during vertebrate evolution provided a vital neuroprotective function to myelin-forming CNS glia. PMID:16449196

  3. Insights into mechanisms of central nervous system myelination using zebrafish.

    PubMed

    Czopka, Tim

    2016-03-01

    Myelin is the multi-layered membrane that surrounds most axons and is produced by oligodendrocytes in the central nervous system (CNS). In addition to its important role in enabling rapid nerve conduction, it has become clear in recent years that myelin plays additional vital roles in CNS function. Myelinating oligodendrocytes provide metabolic support to axons and active myelination is even involved in regulating forms of learning and memory formation. However, there are still large gaps in our understanding of how myelination by oligodendrocytes is regulated. The small tropical zebrafish has become an increasingly popular model organism to investigate many aspects of nervous system formation, function, and regeneration. This is mainly due to two approaches for which the zebrafish is an ideally suited vertebrate model--(1) in vivo live cell imaging using vital dyes and genetically encoded reporters, and (2) gene and target discovery using unbiased screens. This review summarizes how the use of zebrafish has helped understand mechanisms of oligodendrocyte behavior and myelination in vivo and discusses the potential use of zebrafish to shed light on important future questions relating to myelination in the context of CNS development, function and repair.

  4. Progesterone Synthesis in the Nervous System: Implications for Myelination and Myelin Repair

    PubMed Central

    Schumacher, Michael; Hussain, Rashad; Gago, Nathalie; Oudinet, Jean-Paul; Mattern, Claudia; Ghoumari, Abdel M.

    2011-01-01

    Progesterone is well known as a female reproductive hormone and in particular for its role in uterine receptivity, implantation, and the maintenance of pregnancy. However, neuroendocrine research over the past decades has established that progesterone has multiple functions beyond reproduction. Within the nervous system, its neuromodulatory and neuroprotective effects are much studied. Although progesterone has been shown to also promote myelin repair, its influence and that of other steroids on myelination and remyelination is relatively neglected. Reasons for this are that hormonal influences are still not considered as a central problem by most myelin biologists, and that neuroendocrinologists are not sufficiently concerned with the importance of myelin in neuron functions and viability. The effects of progesterone in the nervous system involve a variety of signaling mechanisms. The identification of the classical intracellular progesterone receptors as therapeutic targets for myelin repair suggests new health benefits for synthetic progestins, specifically designed for contraceptive use and hormone replacement therapies. There are also major advantages to use natural progesterone in neuroprotective and myelin repair strategies, because progesterone is converted to biologically active metabolites in nervous tissues and interacts with multiple target proteins. The delivery of progesterone however represents a challenge because of its first-pass metabolism in digestive tract and liver. Recently, the intranasal route of progesterone administration has received attention for easy and efficient targeting of the brain. Progesterone in the brain is derived from the steroidogenic endocrine glands or from local synthesis by neural cells. Stimulating the formation of endogenous progesterone is currently explored as an alternative strategy for neuroprotection, axonal regeneration, and myelin repair. PMID:22347156

  5. Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination

    PubMed Central

    da Silva, Tiago Ferreira; Eira, Jessica; Lopes, André T.; Malheiro, Ana R.; Sousa, Vera; Luoma, Adrienne; Avila, Robin L.; Wanders, Ronald J.A.; Just, Wilhelm W.; Kirschner, Daniel A.; Sousa, Mónica M.; Brites, Pedro

    2014-01-01

    Rhizomelic chondrodysplasia punctata (RCDP) is a developmental disorder characterized by hypotonia, cataracts, abnormal ossification, impaired motor development, and intellectual disability. The underlying etiology of RCDP is a deficiency in the biosynthesis of ether phospholipids, of which plasmalogens are the most abundant form in nervous tissue and myelin; however, the role of plasmalogens in the peripheral nervous system is poorly defined. Here, we used mouse models of RCDP and analyzed the consequence of plasmalogen deficiency in peripheral nerves. We determined that plasmalogens are crucial for Schwann cell development and differentiation and that plasmalogen defects impaired radial sorting, myelination, and myelin structure. Plasmalogen insufficiency resulted in defective protein kinase B (AKT) phosphorylation and subsequent signaling, causing overt activation of glycogen synthase kinase 3β (GSK3β) in nerves of mutant mice. Treatment with GSK3β inhibitors, lithium, or 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) restored Schwann cell defects, effectively bypassing plasmalogen deficiency. Our results demonstrate the requirement of plasmalogens for the correct and timely differentiation of Schwann cells and for the process of myelination. In addition, these studies identify a mechanism by which the lack of a membrane phospholipid causes neuropathology, implicating plasmalogens as regulators of membrane and cell signaling. PMID:24762439

  6. Data supporting the role of Fyn in initiating myelination in the peripheral nervous system.

    PubMed

    Miyamoto, Yuki; Tamano, Moe; Torii, Tomohiro; Kawahara, Kazuko; Nakamura, Kazuaki; Tanoue, Akito; Takada, Shuji; Yamauchi, Junji

    2016-06-01

    Transgenic mice, which express active Fyn tyrosine kinase under the control of a glial fibrillary acidic protein promoter, have been produced. This promoter induces protein expression in the initiation stage of myelination in the peripheral nervous system (PNS) "Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development (Yamauchi et al., 2015 [1])". Herein we provide the data regarding myelination-related protein markers and myelin ultrastructure in transgenic mice.

  7. Data supporting the role of Fyn in initiating myelination in the peripheral nervous system

    PubMed Central

    Miyamoto, Yuki; Tamano, Moe; Torii, Tomohiro; Kawahara, Kazuko; Nakamura, Kazuaki; Tanoue, Akito; Takada, Shuji; Yamauchi, Junji

    2016-01-01

    Transgenic mice, which express active Fyn tyrosine kinase under the control of a glial fibrillary acidic protein promoter, have been produced. This promoter induces protein expression in the initiation stage of myelination in the peripheral nervous system (PNS) “Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development (Yamauchi et al., 2015 [1])”. Herein we provide the data regarding myelination-related protein markers and myelin ultrastructure in transgenic mice. PMID:27115022

  8. Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction

    PubMed Central

    Patzig, Julia; Erwig, Michelle S; Tenzer, Stefan; Kusch, Kathrin; Dibaj, Payam; Möbius, Wiebke; Goebbels, Sandra; Schaeren-Wiemers, Nicole; Nave, Klaus-Armin; Werner, Hauke B

    2016-01-01

    Myelination of axons facilitates rapid impulse propagation in the nervous system. The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal aging. However, the molecular cause of many pathological features, including the frequently observed myelin outfoldings, remained unknown. Using label-free quantitative proteomics, we find that the presence of myelin outfoldings correlates with a loss of cytoskeletal septins in myelin. Regulated by phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2)-levels, myelin septins (SEPT2/SEPT4/SEPT7/SEPT8) and the PI(4,5)P2-adaptor anillin form previously unrecognized filaments that extend longitudinally along myelinated axons. By confocal microscopy and immunogold-electron microscopy, these filaments are localized to the non-compacted adaxonal myelin compartment. Genetic disruption of these filaments in Sept8-mutant mice causes myelin outfoldings as a very specific neuropathology. Septin filaments thus serve an important function in scaffolding the axon/myelin-unit, evidently a late stage of myelin maturation. We propose that pathological or aging-associated diminishment of the septin/anillin-scaffold causes myelin outfoldings that impair the normal nerve conduction velocity. DOI: http://dx.doi.org/10.7554/eLife.17119.001 PMID:27504968

  9. Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction.

    PubMed

    Patzig, Julia; Erwig, Michelle S; Tenzer, Stefan; Kusch, Kathrin; Dibaj, Payam; Möbius, Wiebke; Goebbels, Sandra; Schaeren-Wiemers, Nicole; Nave, Klaus-Armin; Werner, Hauke B

    2016-01-01

    Myelination of axons facilitates rapid impulse propagation in the nervous system. The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal aging. However, the molecular cause of many pathological features, including the frequently observed myelin outfoldings, remained unknown. Using label-free quantitative proteomics, we find that the presence of myelin outfoldings correlates with a loss of cytoskeletal septins in myelin. Regulated by phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2)-levels, myelin septins (SEPT2/SEPT4/SEPT7/SEPT8) and the PI(4,5)P2-adaptor anillin form previously unrecognized filaments that extend longitudinally along myelinated axons. By confocal microscopy and immunogold-electron microscopy, these filaments are localized to the non-compacted adaxonal myelin compartment. Genetic disruption of these filaments in Sept8-mutant mice causes myelin outfoldings as a very specific neuropathology. Septin filaments thus serve an important function in scaffolding the axon/myelin-unit, evidently a late stage of myelin maturation. We propose that pathological or aging-associated diminishment of the septin/anillin-scaffold causes myelin outfoldings that impair the normal nerve conduction velocity. PMID:27504968

  10. The transcriptome of mouse central nervous system myelin

    PubMed Central

    Thakurela, Sudhir; Garding, Angela; Jung, Ramona B.; Müller, Christina; Goebbels, Sandra; White, Robin; Werner, Hauke B.; Tiwari, Vijay K.

    2016-01-01

    Rapid nerve conduction in the CNS is facilitated by insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics remains elusive. Here we performed a comprehensive transcriptome analysis (RNA-seq) of myelin biochemically purified from mouse brains at various ages and find a surprisingly large pool of transcripts enriched in myelin. Further computational analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting a highly selective incorporation of mRNAs into the myelin compartment. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months were minor. We suggest that this transcript pool enables myelin turnover and the local adaptation of individual pre-existing myelin sheaths. PMID:27173133

  11. The transcriptome of mouse central nervous system myelin.

    PubMed

    Thakurela, Sudhir; Garding, Angela; Jung, Ramona B; Müller, Christina; Goebbels, Sandra; White, Robin; Werner, Hauke B; Tiwari, Vijay K

    2016-01-01

    Rapid nerve conduction in the CNS is facilitated by insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics remains elusive. Here we performed a comprehensive transcriptome analysis (RNA-seq) of myelin biochemically purified from mouse brains at various ages and find a surprisingly large pool of transcripts enriched in myelin. Further computational analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting a highly selective incorporation of mRNAs into the myelin compartment. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months were minor. We suggest that this transcript pool enables myelin turnover and the local adaptation of individual pre-existing myelin sheaths. PMID:27173133

  12. Neurotrophins are key mediators of the myelination program in the peripheral nervous system

    PubMed Central

    Chan, Jonah R.; Cosgaya, José Miguel; Wu, Yong Jian; Shooter, Eric M.

    2001-01-01

    Although knowledge of the functions of neurotrophins has advanced rapidly in recent years, studies concerning the involvement of neurotrophins in glial–neuronal interactions rarely extend further than their roles in supporting the survival and differentiation of neuronal cells. In this study endogenous brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) were identified in Schwann cell/dorsal root ganglia neuronal cocultures and shown to modulate the myelination program of the peripheral nervous system. The differential expression of BDNF and NT3 were examined and compared with the expression profiles of myelin proteins in the cocultures throughout the myelination process. BDNF levels correlated with active myelin formation, whereas NT3 expression was initially high and then down regulated throughout the proliferation and premyelination periods. Addition of exogenous BDNF enhanced myelination, whereas the removal of the endogenous BDNF by using the BDNF receptor TrkB-Fc fusion protein inhibited the formation of mature myelin internodes. Interestingly, exogenous NT3 significantly inhibited myelination, whereas the removal of the endogenous NT3 by using the NT3 receptor TrkC-Fc fusion protein resulted in an enhancement similar to that obtained with the addition of BDNF. In addition, in vivo studies were performed during the development of the mouse sciatic nerve. Subcutaneous injections of BDNF resulted in an enhancement of myelin formation in the sciatic nerve, whereas the removal of the endogenous BDNF dramatically inhibited myelination. Injections of NT3 inhibited myelin formation, and the removal of the endogenous NT3 enhanced myelination. These results demonstrate that BDNF and NT3 possess different modulatory roles in the myelination program of the peripheral nervous system and that their mechanisms of action are specific and highly regulated. PMID:11717413

  13. The Lin28/let-7 axis is critical for myelination in the peripheral nervous system

    PubMed Central

    Gökbuget, Deniz; Pereira, Jorge A.; Bachofner, Sven; Marchais, Antonin; Ciaudo, Constance; Stoffel, Markus; Schulte, Johannes H.; Suter, Ueli

    2015-01-01

    MicroRNAs (miRNAs) are crucial regulators of myelination in the peripheral nervous system (PNS). However, the miRNAs species involved and the underlying mechanisms are largely unknown. We found that let-7 miRNAs are highly abundant during PNS myelination and that their levels are inversely correlated to the expression of lin28 homolog B (Lin28B), an antagonist of let-7 accumulation. Sustained expression of Lin28B and consequently reduced levels of let-7 miRNAs results in a failure of Schwann cell myelination in transgenic mouse models and in cell culture. Subsequent analyses revealed that let-7 miRNAs promote expression of the myelination-driving master transcription factor Krox20 (also known as Egr2) through suppression of myelination inhibitory Notch signalling. We conclude that the Lin28B/let-7 axis acts as a critical driver of PNS myelination, in particular by regulating myelination onset, identifying this pathway also as a potential therapeutic target in demyelinating diseases. PMID:26466203

  14. The Lin28/let-7 axis is critical for myelination in the peripheral nervous system.

    PubMed

    Gökbuget, Deniz; Pereira, Jorge A; Bachofner, Sven; Marchais, Antonin; Ciaudo, Constance; Stoffel, Markus; Schulte, Johannes H; Suter, Ueli

    2015-10-14

    MicroRNAs (miRNAs) are crucial regulators of myelination in the peripheral nervous system (PNS). However, the miRNAs species involved and the underlying mechanisms are largely unknown. We found that let-7 miRNAs are highly abundant during PNS myelination and that their levels are inversely correlated to the expression of lin28 homolog B (Lin28B), an antagonist of let-7 accumulation. Sustained expression of Lin28B and consequently reduced levels of let-7 miRNAs results in a failure of Schwann cell myelination in transgenic mouse models and in cell culture. Subsequent analyses revealed that let-7 miRNAs promote expression of the myelination-driving master transcription factor Krox20 (also known as Egr2) through suppression of myelination inhibitory Notch signalling. We conclude that the Lin28B/let-7 axis acts as a critical driver of PNS myelination, in particular by regulating myelination onset, identifying this pathway also as a potential therapeutic target in demyelinating diseases.

  15. Myelin, DIGs, and membrane rafts in the central nervous system.

    PubMed

    Dupree, Jeffrey L; Pomicter, Anthony D

    2010-04-01

    Over the past 40 years our understanding of the organization of cell membranes has changed dramatically. Membranes are no longer viewed as a homogenous sea of phospholipids studded with randomly positioned islands of proteins. Our current view of the membrane involves the formation of small lipid clusters, comprised mainly of cholesterol and sphingolipids, known as membrane rafts. These lipid clusters apparently include and exclude specific proteins leading to the hypothesis that these domains (1) regulate cellular polarity and compartmentalization through trafficking and sorting, (2) provide platforms for cellular signaling and adhesion, and (3) function as cellular gate keepers. Tremendous controversy surrounds the concept of membrane rafts primarily because these small, highly dynamic entities are too small to be observed with traditional microscopic methods and the most utilized approach for raft analysis relies on poorly quantified, inconsistent biochemical extractions. New analytical approaches are being developed and applied to the study of membrane rafts and these techniques provide great promise for furthering our understanding of these enigmatic domains. In this review we will provide a brief summary of the current understanding of membrane rafts, utilizing the CNS myelin literature for illustrative purposes, and present caveats that should be considered when studying these domains. PMID:19379822

  16. Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system

    PubMed Central

    Schmitt, Sebastian; Snaidero, Nicolas; Mitkovski, Mišo; Velte, Caroline; Brückner, Bastian R.; Alexopoulos, Ioannis; Czopka, Tim; Jung, Sang Y.; Rhee, Jeong S.; Janshoff, Andreas; Witke, Walter; Schaap, Iwan A.T.; Lyons, David A.; Simons, Mikael

    2016-01-01

    Summary During central nervous system development, oligodendrocytes wrap their plasma membrane around axons to generate multi-lamellar myelin sheaths. To drive growth at the leading edge of myelin at the interface with the axon, mechanical forces are necessary, but the underlying mechanisms are not known. Using an interdisciplinary approach that combines morphological, genetic and biophysical analyses, we identified a key role for actin filament network turnover in myelin growth. At the onset of myelin biogenesis, F-actin is redistributed to the leading edge, where its polymerization-based forces push out non-adhesive and motile protrusions. F-actin disassembly converts protrusions into sheets by reducing surface tension and in turn inducing membrane spreading and adhesion. We identified the actin depolymerizing factor ADF/Cofilin1, which mediates high F-actin turnover rates, as essential factor in this process. We propose that F-actin turnover is the driving force in myelin wrapping by regulating repetitive cycles of leading edge protrusion and spreading. PMID:26166299

  17. Axonal selection and myelin sheath generation in the central nervous system.

    PubMed

    Simons, Mikael; Lyons, David A

    2013-08-01

    The formation of myelin in the central nervous system is a multi-step process that involves coordinated cell-cell interactions and dramatic changes in plasma membrane architecture. First, oligodendrocytes send our numerous highly ramified processes to sample the axonal environment and decide which axon(s) to select for myelination. After this decision is made and individual axon to oligodendrocyte contact has been established, the exploratory process of the oligodendrocyte is converted into a flat sheath that spreads and winds along and around its associated axon to generate a multilayered membrane stack. By compaction of the opposing extracellular layers of membrane and extrusion of almost all cytoplasm from the intracellular domain of the sheath, the characteristic membrane-rich multi-lamellar structure of myelin is formed. Here we highlight recent advances in identifying biophysical and signalling based mechanisms that are involved in axonal selection and myelin sheath generation by oligodendrocytes. A thorough understanding of the mechanisms underlying these events is a prerequisite for the design of novel myelin repair strategies in demyelinating and dysmyelinating diseases.

  18. Proteolipid protein cannot replace P0 protein as the major structural protein of peripheral nervous system myelin.

    PubMed

    Yin, Xinghua; Kiryu-Seo, Sumiko; Kidd, Grahame J; Feltri, M Laura; Wrabetz, Lawrence; Trapp, Bruce D

    2015-01-01

    The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when proteolipid protein (PLP) replaced P0 protein as the most abundant protein of CNS myelin. However, PLP did not replace P0 in peripheral nervous system (PNS) myelin. To investigate the possible consequences of a PLP to P0 shift in PNS myelin, we engineered mice to express PLP instead of P0 in PNS myelin (PLP-PNS mice). PLP-PNS mice had severe neurological disabilities and died between 3 and 6 months of age. Schwann cells in sciatic nerves from PLP-PNS mice sorted axons into one-to-one relationships but failed to form myelin internodes. Mice with equal amounts of P0 and PLP had normal PNS myelination and lifespans similar to wild-type (WT) mice. When PLP was overexpressed with one copy of the P0 gene, sciatic nerves were hypomyelinated; mice displayed motor deficits, but had normal lifespans. These data support the hypothesis that while PLP can co-exist with P0 in PNS myelin, PLP cannot replace P0 as the major structural protein of PNS myelin. PMID:25066805

  19. Proteolipid protein cannot replace P0 protein as the major structural protein of peripheral nervous system myelin

    PubMed Central

    Yin, Xinghua; Kiryu-Seo, Sumiko; Kidd, Grahame J.; Feltri, M. Laura; Wrabetz, Lawrence; Trapp, Bruce D.

    2014-01-01

    The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when proteolipid protein (PLP) replaced P0 protein as the most abundant protein of CNS myelin. However, PLP did not replace P0 in peripheral nervous system (PNS) myelin. To investigate the possible consequences of a PLP to P0 shift in PNS myelin, we engineered mice to express PLP instead of P0 in PNS myelin (PLP-PNS mice). PLP-PNS mice had severe neurological disabilities and died between 3 and 6 months of age. Schwann cells in sciatic nerves from PLP-PNS mice sorted axons into one-to-one relationships but failed to form myelin internodes. Mice with equal amounts of P0 and PLP had normal PNS myelination and lifespans similar to wild-type (WT) mice. When PLP was overexpressed with one copy of the P0 gene, sciatic nerves were hypomyelinated; mice displayed motor deficits but had normal lifespans. These data support the hypothesis that while PLP can co-exist with P0 in PNS myelin, PLP cannot replace P0 as the major structural protein of PNS myelin. PMID:25066805

  20. In Vivo Evidence That TRAF4 Is Required for Central Nervous System Myelin Homeostasis

    PubMed Central

    Blaise, Sébastien; Kneib, Marie; Rousseau, Adrien; Gambino, Frederic; Chenard, Marie-Pierre; Messadeq, Nadia; Muckenstrum, Martine; Alpy, Fabien; Tomasetto, Catherine; Humeau, Yann; Rio, Marie-Christine

    2012-01-01

    Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are major signal transducers for the TNF and interleukin-1/Toll-like receptor superfamilies. However, TRAF4 does not fit the paradigm of TRAF function in immune and inflammatory responses. Its physiological and molecular functions remain poorly understood. Behavorial analyses show that TRAF4-deficient mice (TRAF4-KO) exhibit altered locomotion coordination typical of ataxia. TRAF4-KO central nervous system (CNS) ultrastructure shows strong myelin perturbation including disorganized layers and disturbances in paranode organization. TRAF4 was previously reported to be expressed by CNS neurons. Using primary cell culture, we now show that TRAF4 is also expressed by oligodendrocytes, at all stages of their differentiation. Moreover, histology and electron microscopy show degeneration of a high number of Purkinje cells in TRAF4-KO mice, that was confirmed by increased expression of the Bax pro-apoptotic marker (immunofluorescence), TUNEL analysis, and caspase-3 activation and PARP1 cleavage (western blotting). Consistent with this phenotype, MAG and NogoA, two myelin-induced neurite outgrowth inhibitors, and their neuron partners, NgR and p75NTR were overexpressed (Q-RT-PCR and western blotting). The strong increased phosphorylation of Rock2, a RhoA downstream target, indicated that the NgR/p75NTR/RhoA signaling pathway, known to induce actin cytoskeleton rearrangement that favors axon regeneration inhibition and neuron apoptosis, is activated in the absence of TRAF4 (western blotting). Altogether, these results provide conclusive evidence for the pivotal contribution of TRAF4 to myelination and to cerebellar homeostasis, and link the loss of TRAF4 function to demyelinating or neurodegenerative diseases. PMID:22363515

  1. Signaling through ERK1/2 controls myelin thickness during myelin repair in the adult central nervous system.

    PubMed

    Fyffe-Maricich, Sharyl L; Schott, Alexandra; Karl, Molly; Krasno, Janet; Miller, Robert H

    2013-11-20

    Oligodendrocytes, the myelin-forming cells of the CNS, exquisitely tailor the thickness of individual myelin sheaths to the diameter of their target axons to maximize the speed of action potential propagation, thus ensuring proper neuronal connectivity and function. Following demyelinating injuries to the adult CNS, newly formed oligodendrocytes frequently generate new myelin sheaths. Following episodes of demyelination such as those that occur in patients with multiple sclerosis, however, the matching of myelin thickness to axon diameter fails leaving remyelinated axons with thin myelin sheaths potentially compromising function and leaving axons vulnerable to damage. How oligodendrocytes determine the appropriate thickness of myelin for an axon of defined size during repair is unknown and identifying the signals that regulate myelin thickness has obvious therapeutic implications. Here, we show that sustained activation of extracellular-regulated kinases 1 and 2 (ERK1/2) in oligodendrocyte lineage cells results in accelerated myelin repair after injury, and is sufficient for the generation of thick myelin sheaths around remyelinated axons in the adult mouse spinal cord. Our findings suggest a model where ERK1/2 MAP kinase signaling acts as a myelin thickness rheostat that instructs oligodendrocytes to generate axon-appropriate quantities of myelin.

  2. In Vivo Quantification of Myelin Changes in the Vertebrate Nervous System

    PubMed Central

    Wang, Yanming; Wu, Chunying; Caprariello, Andrew V.; Somoza, Eduardo; Zhu, Wenxia; Wang, Changning; Miller, Robert H.

    2010-01-01

    Destruction or changes associated with myelin membranes in the CNS play a key role in the pathogenesis of multiple sclerosis and other related neurodegenerative disorders. A long-standing goal has been to detect and quantify myelin content in vivo. For this reason, we have developed a myelin-imaging technique based on positron emission tomography (PET). PET is a quantitative imaging modality that has been widely used in clinical settings for direct assessment of biological processes at the molecular level. However, lack of myelin-imaging probes has hampered the use of PET for imaging of myelination in the CNS. Here, we report a myelin-imaging agent, termed Case Imaging Compound (CIC) that readily penetrates the blood– brain barrier and preferentially localizes to myelinated regions of the brain. After radiolabeling with positron-emitting carbon-11, [11C]CIC–PET was conducted in longitudinal studies using a lysolethicin-induced rat model of focal demyelination and subsequent remyelination. Quantitative analysis showed that the retention of [11C]CIC correlates with the level of demyelination/remyelination. These studies indicate that, for the first time, [11C]CIC–PET can be used as an imaging marker of myelination, which has the potential to be translated into clinical studies in multiple sclerosis and other myelin-related diseases for early diagnosis, subtyping, and efficacy evaluation of therapeutic treatments aimed at myelin repair. PMID:19923299

  3. Characterization of the M2 autoantigen of central nervous system (CNS) myelin as a glycoproteins(s) also expressed on oligodendrocyte membrane

    SciTech Connect

    Lebar, R.; Lubetzki, C.; Vincent, C.; Lombrail, P.; Boutry, J.M.

    1986-03-01

    Guinea pigs immunized with homologous brain tissue develop an acute experimental allergic encephalomyelitis and their sera contain demyelinating antibodies. These antibodies were used to characterize the target: the unidentified autoantigen M2. Using both the Dot immunobinding technique and autoradiography of immunoprecipitates formed with radiolabelled guinea-pig myelin and analyzed in SDS acrylamide gel electrophoresis, M2 was found to be a component of CNS myelin and not peripheral nervous system (PNS) myelin. In the Dot technique anti-M2 serum did not react with myelin basic protein (BP), proteolipid and galactocerebroside (GC). On electrophoresis, in reducing and non reducing conditions, M2 appeared as two CNS myelin protein bands at the 27,000 and 54,000 molecular weight levels, distinct from the CNS myelin major protein bands of proteolipid protein and BP. Affinity chromatography of CNS myelin on wheat germ agglutinin Sepharose showed that M2 bands were of glycoprotein nature. The same M2 bands were formed with guinea pig antibodies and rat, rabbit or bovine CNS myelin. The same type of anti-M2 antibodies were induced in rabbits immunized with homologous CNS tissue. As a component of myelin, M2 was present in white matter tracts of CNS tissue sections tested by immunofluorescence. Furthermore, M2 was expressed on rat oligodendrocyte membrane in one day and 8 day in vitro cultures.

  4. Molecular anatomy and genetics of myelin proteins in the peripheral nervous system.

    PubMed Central

    Snipes, G J; Suter, U

    1995-01-01

    Myelin contains a number of proteins, the major examples of which are protein zero (Po), P2 protein, peripheral myelin protein 22 (PMP22), myelin basic proteins (MBPs), myelin-associated glycoprotein (MAG) and the recently described connexin 32 (Cx32). This list is probably still incomplete. The localisation and possible functions of these proteins are reviewed. In the past few years a number of inherited demyelinating neuropathies in mice and the human have been shown to be due to mutations affecting the genes PMP22, Po and Cx32 so that it has become possible to characterise the molecular pathology of the majority of these disorders. This has provided important insights into the relationships between the structure of myelin and the function of its constituent proteins. Images Fig. 1 PMID:7559122

  5. Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system.

    PubMed

    Nawaz, Schanila; Sánchez, Paula; Schmitt, Sebastian; Snaidero, Nicolas; Mitkovski, Mišo; Velte, Caroline; Brückner, Bastian R; Alexopoulos, Ioannis; Czopka, Tim; Jung, Sang Y; Rhee, Jeong S; Janshoff, Andreas; Witke, Walter; Schaap, Iwan A T; Lyons, David A; Simons, Mikael

    2015-07-27

    During CNS development, oligodendrocytes wrap their plasma membrane around axons to generate multilamellar myelin sheaths. To drive growth at the leading edge of myelin at the interface with the axon, mechanical forces are necessary, but the underlying mechanisms are not known. Using an interdisciplinary approach that combines morphological, genetic, and biophysical analyses, we identified a key role for actin filament network turnover in myelin growth. At the onset of myelin biogenesis, F-actin is redistributed to the leading edge, where its polymerization-based forces push out non-adhesive and motile protrusions. F-actin disassembly converts protrusions into sheets by reducing surface tension and in turn inducing membrane spreading and adhesion. We identified the actin depolymerizing factor ADF/cofilin1, which mediates high F-actin turnover rates, as an essential factor in this process. We propose that F-actin turnover is the driving force in myelin wrapping by regulating repetitive cycles of leading edge protrusion and spreading.

  6. Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system

    PubMed Central

    Çolakoğlu, Gülsen; Bergstrom-Tyrberg, Ulrika; Berglund, Erik O.; Ranscht, Barbara

    2014-01-01

    Myelin, a multilayered membrane sheath formed by oligodendrocytes around axons in the CNS, enables rapid nerve impulse conduction and sustains neuronal health. The signals exchanged between axons and oligodendrocytes in myelin remain to be fully elucidated. Here we provide genetic evidence for multiple and critical functions of Contactin-1 in central myelin. We document dynamic Contactin-1 expression on oligodendrocytes in vivo, and progressive accumulation at nodes of Ranvier and paranodes during postnatal mouse development. Nodal and paranodal expression stabilized in mature myelin, but overall membranous expression diminished. Contactin-1–deficiency disrupted paranodal junction formation as evidenced by loss of Caspr, mislocalized potassium Kv1.2 channels, and abnormal myelin terminal loops. Reduced numbers and impaired maturation of sodium channel clusters accompanied this phenotype. Histological, electron microscopic, and biochemical analyses uncovered significant hypomyelination in Contactin-1–deficient central nerves, with up to 60% myelin loss. Oligodendrocytes were present in normal numbers, albeit a minor population of neuronal/glial antigen 2-positive (NG2+) progenitors lagged in maturation by postnatal day 18, when the mouse null mutation was lethal. Major contributing factors to hypomyelination were defects in the generation and organization of myelin membranes, as judged by electron microscopy and quantitative analysis of oligodendrocyte processes labeled by GFP transgenically expressed from the proteolipid protein promoter. These data reveal that Contactin-1 regulates both myelin formation and organization of nodal and paranodal domains in the CNS. These multiple roles distinguish central Contactin-1 functions from its specific role at paranodes in the periphery, and emphasize mechanistic differences in central and peripheral myelination. PMID:24385581

  7. Gas6 Promotes Oligodendrogenesis and Myelination in the Adult Central Nervous System and After Lysolecithin-Induced Demyelination

    PubMed Central

    Goudarzi, Salman; Rivera, Andrea; Butt, Arthur M.

    2016-01-01

    A key aim of therapy for multiple sclerosis (MS) is to promote the regeneration of oligodendrocytes and remyelination in the central nervous system (CNS). The present study provides evidence that the vitamin K-dependent protein growth arrest specific 6 (Gas6) promotes such repair in in vitro cultures of mouse optic nerve and cerebellum. We first determined expression of Gas6 and TAM (Tyro3, Axl, Mer) receptors in the mouse CNS, with all three TAM receptors increasing in expression through postnatal development, reaching maximal levels in the adult. Treatment of cultured mouse optic nerves with Gas6 resulted in significant increases in oligodendrocyte numbers as well as expression of myelin basic protein (MBP). Gas6 stimulation also resulted in activation of STAT3 in optic nerves as well as downregulation of multiple genes involved in MS development, including matrix metalloproteinase-9 (MMP9), which may decrease the integrity of the blood–brain barrier and is found upregulated in MS lesions. The cytoprotective effects of Gas6 were examined in in vitro mouse cerebellar slice cultures, where lysolecithin was used to induce demyelination. Cotreatment of cerebellar slices with Gas6 significantly attenuated demyelination as determined by MBP immunostaining, and Gas6 activated Tyro3 receptor through its phosphorylation. In conclusion, these results demonstrate that Gas6/TAM signaling stimulates the generation of oligodendrocytes and increased myelin production via Tyro3 receptor in the adult CNS, including repair after demyelinating injury. Furthermore, the effects of Gas6 on STAT3 signaling and matrix MMP9 downregulation indicate potential glial cell repair and immunoregulatory roles for Gas6, indicating that Gas6-TAM signaling could be a potential therapeutic target in MS and other neuropathologies. PMID:27630207

  8. Gas6 Promotes Oligodendrogenesis and Myelination in the Adult Central Nervous System and After Lysolecithin-Induced Demyelination.

    PubMed

    Goudarzi, Salman; Rivera, Andrea; Butt, Arthur M; Hafizi, Sassan

    2016-10-01

    A key aim of therapy for multiple sclerosis (MS) is to promote the regeneration of oligodendrocytes and remyelination in the central nervous system (CNS). The present study provides evidence that the vitamin K-dependent protein growth arrest specific 6 (Gas6) promotes such repair in in vitro cultures of mouse optic nerve and cerebellum. We first determined expression of Gas6 and TAM (Tyro3, Axl, Mer) receptors in the mouse CNS, with all three TAM receptors increasing in expression through postnatal development, reaching maximal levels in the adult. Treatment of cultured mouse optic nerves with Gas6 resulted in significant increases in oligodendrocyte numbers as well as expression of myelin basic protein (MBP). Gas6 stimulation also resulted in activation of STAT3 in optic nerves as well as downregulation of multiple genes involved in MS development, including matrix metalloproteinase-9 (MMP9), which may decrease the integrity of the blood-brain barrier and is found upregulated in MS lesions. The cytoprotective effects of Gas6 were examined in in vitro mouse cerebellar slice cultures, where lysolecithin was used to induce demyelination. Cotreatment of cerebellar slices with Gas6 significantly attenuated demyelination as determined by MBP immunostaining, and Gas6 activated Tyro3 receptor through its phosphorylation. In conclusion, these results demonstrate that Gas6/TAM signaling stimulates the generation of oligodendrocytes and increased myelin production via Tyro3 receptor in the adult CNS, including repair after demyelinating injury. Furthermore, the effects of Gas6 on STAT3 signaling and matrix MMP9 downregulation indicate potential glial cell repair and immunoregulatory roles for Gas6, indicating that Gas6-TAM signaling could be a potential therapeutic target in MS and other neuropathologies. PMID:27630207

  9. Major isoform of zebrafish P0 is a 23.5 kDa myelin glycoprotein expressed in selected white matter tracts of the central nervous system.

    PubMed

    Bai, Qing; Sun, Ming; Stolz, Donna B; Burton, Edward A

    2011-06-01

    The zebrafish mpz gene, encoding the ortholog of mammalian myelin protein zero, is expressed in oligodendrocytes of the zebrafish central nervous system (CNS). The putative gene product, P0, has been implicated in promoting axonal regeneration in addition to its proposed structural functions in compact myelin. We raised novel zebrafish P0-specific antibodies and established that P0 is a 23.5 kDa glycoprotein containing a 3 kDa N-linked carbohydrate moiety. P0 was localized to myelin sheaths surrounding axons, but was not detected in the cell bodies or proximal processes of oligodendrocytes. Many white matter tracts in the adult zebrafish CNS were robustly immunoreactive for P0, including afferent visual and olfactory pathways, commissural and longitudinal tracts of the brain, and selected ascending and descending tracts of the spinal cord. P0 was first detected during development in premyelinating oligodendrocytes of the ventral hindbrain at 48 hours postfertilization (hpf). By 72 hpf, short segments of longitudinally oriented P0-immunoreactive myelinating axons were seen in the hindbrain; expression in the spinal cord, optic pathways, hindbrain commissures, midbrain, and peripheral nervous system followed. The mpz transcript was found to be alternatively spliced, giving rise to P0 isoforms with alternative C-termini. The 23.5 kDa isoform was most abundant in the CNS, but other isoforms predominated in the myelin sheath surrounding the Mauthner axon. These data provide a detailed account of P0 expression and demonstrate novel P0 isoforms, which may have discrete functional properties. The restriction of P0 immunoreactivity to myelin sheaths indicates that the protein is subject to stringent intracellular compartmentalization, which likely occurs through posttranslational mechanisms.

  10. Identification of the Low Density Lipoprotein (LDL) Receptor-related Protein-1 Interactome in Central Nervous System Myelin Suggests a Role in the Clearance of Necrotic Cell Debris*

    PubMed Central

    Fernandez-Castaneda, Anthony; Arandjelovic, Sanja; Stiles, Travis L.; Schlobach, Ryan K.; Mowen, Kerri A.; Gonias, Steven L.; Gaultier, Alban

    2013-01-01

    In the central nervous system (CNS), fast neuronal signals are facilitated by the oligodendrocyte-produced myelin sheath. Oligodendrocyte turnover or injury generates myelin debris that is usually promptly cleared by phagocytic cells. Failure to remove dying oligodendrocytes leads to accumulation of degraded myelin, which, if recognized by the immune system, may contribute to the development of autoimmunity in diseases such as multiple sclerosis. We recently identified low density lipoprotein receptor-related protein-1 (LRP1) as a novel phagocytic receptor for myelin debris. Here, we report characterization of the LRP1 interactome in CNS myelin. Fusion proteins were designed corresponding to the extracellular ligand-binding domains of LRP1. LRP1 partners were isolated by affinity purification and characterized by mass spectrometry. We report that LRP1 binds intracellular proteins via its extracellular domain and functions as a receptor for necrotic cells. Peptidyl arginine deiminase-2 and cyclic nucleotide phosphodiesterase are novel LRP1 ligands identified in our screen, which interact with full-length LRP1. Furthermore, the extracellular domain of LRP1 is a target of peptidyl arginine deiminase-2-mediated deimination in vitro. We propose that LRP1 functions as a receptor for endocytosis of intracellular components released during cellular damage and necrosis. PMID:23264627

  11. Role of IL-33 and ST2 signalling pathway in multiple sclerosis: expression by oligodendrocytes and inhibition of myelination in central nervous system.

    PubMed

    Allan, Debbie; Fairlie-Clarke, Karen J; Elliott, Christina; Schuh, Cornelia; Barnett, Susan C; Lassmann, Hans; Linnington, Christopher; Jiang, Hui-Rong

    2016-07-26

    Recent research findings have provided convincing evidence indicating a role for Interleukin-33 (IL-33) signalling pathway in a number of central nervous system (CNS) diseases including multiple sclerosis (MS) and Alzheimer's disease. However, the exact function of IL-33 molecule within the CNS under normal and pathological conditions is currently unknown. In this study, we have mapped cellular expression of IL-33 and its receptor ST2 by immunohistochemistry in the brain tissues of MS patients and appropriate controls; and investigated the functional significance of these findings in vitro using a myelinating culture system. Our results demonstrate that IL-33 is expressed by neurons, astrocytes and microglia as well as oligodendrocytes, while ST2 is expressed in the lesions by oligodendrocytes and within and around axons. Furthermore, the expression levels and patterns of IL-33 and ST2 in the lesions of acute and chronic MS patient brain samples are enhanced compared with the healthy brain tissues. Finally, our data using rat myelinating co-cultures suggest that IL-33 may play an important role in MS development by inhibiting CNS myelination.

  12. Distribution of monocarboxylate transporters in the peripheral nervous system suggests putative roles in lactate shuttling and myelination.

    PubMed

    Domènech-Estévez, Enric; Baloui, Hasna; Repond, Cendrine; Rosafio, Katia; Médard, Jean-Jacques; Tricaud, Nicolas; Pellerin, Luc; Chrast, Roman

    2015-03-11

    Lactate, a product of glycolysis, has been shown to play a key role in the metabolic support of neurons/axons in the CNS by both astrocytes and oligodendrocytes through monocarboxylate transporters (MCTs). Despite such importance in the CNS, little is known about MCT expression and lactate function in the PNS. Here we show that mouse MCT1, MCT2, and MCT4 are expressed in the PNS. While DRG neurons express MCT1, myelinating Schwann cells (SCs) coexpress MCT1 and MCT4 in a domain-specific fashion, mainly in regions of noncompact myelin. Interestingly, SC-specific downregulation of MCT1 expression in rat neuron/SC cocultures led to increased myelination, while its downregulation in neurons resulted in a decreased amount of neurofilament. Finally, pure rat SCs grown in the presence of lactate exhibited an increase in the level of expression of the main myelin regulator gene Krox20/Egr2 and the myelin gene P0. These data indicate that lactate homeostasis participates in the regulation of the SC myelination program and reveal that similar to CNS, PNS axon-glial metabolic interactions are most likely mediated by MCTs. PMID:25762662

  13. SJL mice infected with Acanthamoeba castellanii develop central nervous system autoimmunity through the generation of cross-reactive T cells for myelin antigens.

    PubMed

    Massilamany, Chandirasegaran; Marciano-Cabral, Francine; Rocha-Azevedo, Bruno da; Jamerson, Melissa; Gangaplara, Arunakumar; Steffen, David; Zabad, Rana; Illes, Zsolt; Sobel, Raymond A; Reddy, Jay

    2014-01-01

    We recently reported that Acanthamoeba castellanii (ACA), an opportunistic pathogen of the central nervous system (CNS) possesses mimicry epitopes for proteolipid protein (PLP) 139-151 and myelin basic protein 89-101, and that the epitopes induce experimental autoimmune encephalomyelitis (EAE) in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of cross-reactive T cells, predominantly for PLP 139-151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified that PLP 139-151-sensitized lymphocytes generated in infected mice contained a high proportion of T helper 1 cytokine-producing cells, and they can transfer disease to naïve animals. Likewise, the animals first primed with suboptimal dose of PLP 139-151 and later infected with ACA, developed EAE, suggesting that ACA infection can trigger CNS autoimmunity in the presence of preexisting repertoire of autoreactive T cells. Taken together, the data provide novel insights into the pathogenesis of Acanthamoeba infections, and the potential role of infectious agents with mimicry epitopes to self-antigens in the pathogenesis of CNS diseases such as multiple sclerosis.

  14. The human myelin basic protein gene is included within a 179-kilobase transcription unit: Expression in the immune and central nervous systems

    SciTech Connect

    Pribyl, T.M.; Campagnoni, C.W.; Kampf, K.; Kashima, T.; Handley, V.W.; Campagnoni, A.T. ); McMahon, J. )

    1993-11-15

    Two human Golli (for gene expressed in the oligodendrocyte lineage)-MBP (for myelin basic protein) cDNAs have been isolated from a human oligodendroglioma cell line. Analysis of these cDNAs has enabled the authors to determine the entire structure of the human Golli-MBP gene. The Golli-MBP gene, which encompasses the MBP transcription unit, is [approx] 179 kb in length and consists of 10 exons, seven of which constitute the MBP gene. The human Golli-MBP gene contains two transcription start sites, each of which gives rise to a family of alternatively spliced transcipts. At least two Golli-MBP transcripts, containing the first three exons of the gene and one or more MBP exons, are produced from the first transcription start site. The second family of transcripts contains only MBP exons and produces the well-known MBPs. In humans, RNA blot analysis revealed that Golli-MBP transcripts were expressed in fetal thymus, spleen, and human B-cell and macrophage cell lines, as well as in fetal spinal cord. These findings clearly link the expression of exons encoding the autoimmunogen/encephalitogen MBP in the central nervous system to cells and tissues of the immune system through normal expression of the Golli-MBP gene. They also establish that this genetic locus, which includes the MBP gene, is conserved among species, providing further evidence that the MBP transcription unit is an integral part of the Golli transcription unit and suggest that this structural arrangement is important for the genetic function and/or regulation of these genes.

  15. Autonomic Nervous System Disorders

    MedlinePlus

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  16. The sodium channel isoform transition at developing nodes of Ranvier in the peripheral nervous system: dependence on a Genetic program and myelination-induced cluster formation.

    PubMed

    Luo, Songjiang; Jaegle, Martine; Li, Roy; Ehring, George R; Meijer, Dies; Levinson, Simon R

    2014-12-15

    Among sodium channel isoforms, Nav 1.6 is selectively expressed at nodes of Ranvier in both the CNS and the PNS. However, non-Nav 1.6 isoforms such as Nav 1.2 are also present at the CNS nodes in early development but gradually diminish later. It has been proposed that myelination is part of a glia-neuron signaling mechanism that produces this change in nodal isoform expression. The present study used isoform-specific antibodies to demonstrate that, in the PNS, four other neuronal sodium channel isoforms were also clustered at nodes in early development but eventually disappeared during maturation. To study possible roles of myelination in such transitions, we investigated the nodal expression of selected isoforms in the sciatic nerve of the transgenic mouse Oct6(ΔSCE/βgeo) , whose PNS myelination is delayed in the first postnatal week but eventually resumes. We found that delayed myelination retarded the formation of nodal channel clusters and altered the expression-elimination patterns of sodium channel isoforms, resulting in significantly reduced expression levels of non-Nav 1.6 isoforms in such delayed nodes. However, delayed myelination did not significantly affect the gene expression, protein synthesis, or axonal trafficking of any isoform studied. Rather, we found evidence for a developmentally programmed increase in neuronal Nav 1.6 expression with constant or decreasing neuronal expression of other isoforms that were unaffected by delayed myelination. Thus our results suggest that, in the developmental isoform switch of the PNS, myelination does not play a signaling role as that proposed for the CNS but rather serves only to form nodal clusters from existing isoform pools.

  17. The relationship between viral RNA, myelin-specific mRNAs, and demyelination in central nervous system disease during Theiler's virus infection.

    PubMed

    Yamada, M; Zurbriggen, A; Fujinami, R S

    1990-12-01

    The DA strain of Theiler's murine encephalomyelitis virus (DAV) causes a chronic demyelinating disease in susceptible mouse strains. To elucidate the pathogenesis of DAV-induced demyelination, the authors investigated the spatial and chronologic relationship between virus (antigen and RNA), myelin-specific mRNAs, and demyelination in DAV-infected mice using immunohistochemistry, in situ hybridization, and slot blot hybridization analyses. In spinal cord white matter, viral RNA was detected easily in ventral root entry zones 1 to 2 weeks after infection. Viral RNA increased to maximum levels by 4 weeks after infection, which was associated with inflammation and mild demyelination. At 8 to 12 weeks after infection, when demyelination became most extensive, viral RNA was significantly decreased. Demyelination did not chronologically or spatially parallel the presence of viral RNA within the spinal cord. Decrease of myelin-specific mRNAs, including myelin-basic protein and proteolipid protein mRNAs, was observed within the demyelinating lesions with or without detectable viral RNA. These results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination, but later an ongoing immunopathologic process contributes to the presence of extensive demyelination.

  18. The relationship between viral RNA, myelin-specific mRNAs, and demyelination in central nervous system disease during Theiler's virus infection.

    PubMed Central

    Yamada, M.; Zurbriggen, A.; Fujinami, R. S.

    1990-01-01

    The DA strain of Theiler's murine encephalomyelitis virus (DAV) causes a chronic demyelinating disease in susceptible mouse strains. To elucidate the pathogenesis of DAV-induced demyelination, the authors investigated the spatial and chronologic relationship between virus (antigen and RNA), myelin-specific mRNAs, and demyelination in DAV-infected mice using immunohistochemistry, in situ hybridization, and slot blot hybridization analyses. In spinal cord white matter, viral RNA was detected easily in ventral root entry zones 1 to 2 weeks after infection. Viral RNA increased to maximum levels by 4 weeks after infection, which was associated with inflammation and mild demyelination. At 8 to 12 weeks after infection, when demyelination became most extensive, viral RNA was significantly decreased. Demyelination did not chronologically or spatially parallel the presence of viral RNA within the spinal cord. Decrease of myelin-specific mRNAs, including myelin-basic protein and proteolipid protein mRNAs, was observed within the demyelinating lesions with or without detectable viral RNA. These results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination, but later an ongoing immunopathologic process contributes to the presence of extensive demyelination. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:2260633

  19. Central nervous system

    MedlinePlus

    The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

  20. Effects of normal aging on myelin sheath ultrastructures in the somatic sensorimotor system of rats.

    PubMed

    Xie, Fang; Liang, Ping; Fu, Han; Zhang, Jiu-Cong; Chen, Jun

    2014-07-01

    Previous studies have presented qualitative and quantitative data regarding the morphological changes that occur peripherally in myelin sheaths and nerve fibers of rats during their lifespan. However, studies on ultrastructural features of myelinated fibers (MFs) in the central nervous system (CNS) remain limited. In the present study, morphological analyses of the somatic sensorimotor MFs in rats at time‑points between postnatal day 14 and postnatal month (PNM) 26 were conducted using electron microscopy. Significant alterations in the myelin sheath were observed in the sensorimotor system of aging and aged rats, which became aggravated with age. The ultrastructural pattern of myelin lamellae also exhibited age dependence. The transformation of the myelin intraperiod line from complete to incomplete fusion occurred after PNM 5, leading to an expansion of periodicity in myelin lamellae. These pathological changes in the myelin structure occurred very early and showed a significant correlation with age, indicating that myelin was the part of the CNS with the highest susceptibility to the influence of aging, and may be the main target of aging effects. In addition to the myelin breakdown, continued myelin production and remyelination were observed in the aging sensorimotor system, suggesting the presence of endogenous mechanisms of myelin repair.

  1. Nerve Regeneration in the Peripheral Nervous System versus the Central Nervous System and the Relevance to Speech and Hearing after Nerve Injuries

    ERIC Educational Resources Information Center

    Gordon, Tessa; Gordon, Karen

    2010-01-01

    Schwann cells normally form myelin sheaths around axons in the peripheral nervous system (PNS) and support nerve regeneration after nerve injury. In contrast, nerve regeneration in the central nervous system (CNS) is not supported by the myelinating cells known as oligodendrocytes. We have found that: 1) low frequency electrical stimulation can be…

  2. A Phenotypic Culture System for the Molecular Analysis of CNS Myelination in the Spinal Cord

    PubMed Central

    Davis, Hedvika; Gonzalez, Mercedes; Stancescu, Maria; Love, Rachal; Hickman, James J.; Lambert, Stephen

    2014-01-01

    Studies of central nervous system myelination lack defined in vitro models which would effectively dissect molecular mechanisms of myelination that contain cells of the correct phenotype. Here we describe a co-culture of purified motoneurons and oligodendrocyte progenitor cells, isolated from rat embryonic spinal cord using a combination of immunopanning techniques. This model illustrates differentiation of oligodendrocyte progenitors into fully functional mature oligodendrocytes that myelinate axons. It also illustrates a contribution of axons to the rate of oligodendrocyte maturation and myelin gene expression. The defined conditions used allow molecular analysis of distinct stages of myelination and precise manipulation of inductive cues affecting axonal–oligodendrocyte interactions. This phenotypic in vitro myelination model can provide valuable insight into our understanding of demyelinating disorders, such as multiple sclerosis and traumatic diseases such as spinal cord injury where demyelination represents a contributing factor to the pathology of the disorder. PMID:25064806

  3. A phenotypic culture system for the molecular analysis of CNS myelination in the spinal cord.

    PubMed

    Davis, Hedvika; Gonzalez, Mercedes; Stancescu, Maria; Love, Rachal; Hickman, James J; Lambert, Stephen

    2014-10-01

    Studies of central nervous system myelination lack defined in vitro models which would effectively dissect molecular mechanisms of myelination that contain cells of the correct phenotype. Here we describe a co-culture of purified motoneurons and oligodendrocyte progenitor cells, isolated from rat embryonic spinal cord using a combination of immunopanning techniques. This model illustrates differentiation of oligodendrocyte progenitors into fully functional mature oligodendrocytes that myelinate axons. It also illustrates a contribution of axons to the rate of oligodendrocyte maturation and myelin gene expression. The defined conditions used allow molecular analysis of distinct stages of myelination and precise manipulation of inductive cues affecting axonal-oligodendrocyte interactions. This phenotypic in vitro myelination model can provide valuable insight into our understanding of demyelinating disorders, such as multiple sclerosis and traumatic diseases such as spinal cord injury where demyelination represents a contributing factor to the pathology of the disorder.

  4. Subcortical cytoskeleton periodicity throughout the nervous system.

    PubMed

    D'Este, Elisa; Kamin, Dirk; Velte, Caroline; Göttfert, Fabian; Simons, Mikael; Hell, Stefan W

    2016-01-01

    Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought. PMID:26947559

  5. Subcortical cytoskeleton periodicity throughout the nervous system.

    PubMed

    D'Este, Elisa; Kamin, Dirk; Velte, Caroline; Göttfert, Fabian; Simons, Mikael; Hell, Stefan W

    2016-03-07

    Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought.

  6. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting: Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4{sup +} T cells compared

    SciTech Connect

    Ford, A.L.; Goodsall, A.L.; Sedgwick, J.D.

    1995-05-01

    Ramified microglia in the adult central nervous system (CNS) are the principal glial element up-regulating MHC class I and II expression in response to inflammatory events or neuronal damage. A proportion of these cells also express MHC class II constitutively in the normal CNS. The role of microglia as APCs for CD4{sup +} cells extravasating into the CNS remains undefined. In this study, using irradiation bone marrow chimeras in CD45-congenic rats, the phenotype CD45{sup low}CD11b/c{sup +} is shown to identify microglial cells specifically within the CNS. Highly purified populations of microglia and nonmicroglial but CNS-associated macrophages (CD45{sup high}CD11b/c{sup +}) have been obtained directly from the adult CNS, by using flow cytometric sorting. Morphologically, freshly isolated microglia vs other CNS macrophages are quite distinct. Of the two populations recovered from the normal CNS, it is the minority CD45{sup high}CD11 b/c{sup +} transitional macrophage population, and not microglia, that is the effective APC for experimental autoimmune encephalomyelitis-inducing CD4{sup +} myelin basic protein (MBP)-reactive T cells. CD45{sup high}CD11b/c{sup +} CNS macrophages also stimulate MBP-reactive T cells without addition of MBP to culture suggesting presentation of endogenous Ag. This is the first study in which microglia vs other CNS macrophages have been analyzed for APC ability directly from the CNS, with substantial cross-contamination between the two populations eliminated. The heterogeneity of these populations in terms of APC function is clearly demonstrated. Evidence is still lacking that adult CNS microglia have the capacity to interact with and stimulate CD4{sup +} T cells to proliferate or secrete IL-2. 60 refs., 6 figs., 1 tab.

  7. Nervous System Lyme Disease.

    PubMed

    Halperin, John J

    2015-12-01

    Nervous system involvement occurs in 10% to 15% of patients infected with the tick-borne spirochetes Borrelia burgdorferi, B afzelii, and B garinii. Peripheral nervous system involvement is common. Central nervous system (CNS) involvement, most commonly presenting with lymphocytic meningitis, causes modest cerebrospinal fluid (CSF) pleocytosis. Parenchymal CNS infection is rare. If the CNS is invaded, however, measuring local production of anti-B burgdorferi antibodies in the CSF provides a useful marker of infection. Most cases of neuroborreliosis can be cured with oral doxycycline; parenteral regimens should be reserved for patients with particularly severe disease.

  8. The Nervous System Game

    ERIC Educational Resources Information Center

    Corbitt, Cynthia; Carpenter, Molly

    2006-01-01

    For many children, especially those with reading difficulties, a motor-kinesthetic learning activity may be an effective tool to teach complex concepts. With this in mind, the authors developed and tested a game designed to teach fourth- to sixth-grade children some basic principles of nervous system function by allowing the children themselves to…

  9. LGI proteins in the nervous system

    PubMed Central

    Kegel, Linde; Aunin, Eerik; Meijer, Dies; Bermingham, John R.

    2013-01-01

    The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins) play important roles in these processes. They are secreted proteins consisting of an LRR (leucine-rich repeat) domain and a so-called epilepsy-associated or EPTP (epitempin) domain. Both domains are thought to function in protein–protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe) epilepsy) also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions. PMID:23713523

  10. Oligodendrocytes: Myelination and Axonal Support.

    PubMed

    Simons, Mikael; Nave, Klaus-Armin

    2015-06-22

    Myelinated nerve fibers have evolved to enable fast and efficient transduction of electrical signals in the nervous system. To act as an electric insulator, the myelin sheath is formed as a multilamellar membrane structure by the spiral wrapping and subsequent compaction of the oligodendroglial plasma membrane around central nervous system (CNS) axons. Current evidence indicates that the myelin sheath is more than an inert insulating membrane structure. Oligodendrocytes are metabolically active and functionally connected to the subjacent axon via cytoplasmic-rich myelinic channels for movement of macromolecules to and from the internodal periaxonal space under the myelin sheath. This review summarizes our current understanding of how myelin is generated and also the role of oligodendrocytes in supporting the long-term integrity of myelinated axons.

  11. Nervous system Lyme disease.

    PubMed

    Halperin, John J

    2014-01-01

    Lyme disease, the multisystem infectious disease caused by the tick-borne spirochete Borrelia burgdorferi involves the nervous system in 10-15% of affected individuals. Manifestations include lymphocytic meningitis, cranial neuritis, radiculoneuritis, and mononeuropathy multiplex. Encephalopathy, identical to that seen in many systemic inflammatory diseases, can occur during active systemic infection. It is not specific to Lyme disease and only rarely is evidence of nervous system infection. Diagnosis of systemic disease is based on demonstration of specific antibodies in peripheral blood by means of two-tier testing with an ELISA and Western blot. Central nervous system infection often results in specific antibody production in the CSF, demonstrable by comparing spinal fluid to blood serologies. Treatment is straightforward and curative in most instances. Many patients can be treated effectively with oral antibiotics such as doxycycline; in severe CNS infection parenteral treatment with ceftriaxone or other similar agents is highly effective. Treatment should usually be for 2 to at most 4 weeks. Longer treatment adds no therapeutic benefit but does add substantial risk.

  12. Microglia: Architects of the Developing Nervous System.

    PubMed

    Frost, Jeffrey L; Schafer, Dorothy P

    2016-08-01

    Microglia are resident macrophages of the central nervous system (CNS), representing 5-10% of total CNS cells. Recent findings reveal that microglia enter the embryonic brain, take up residence before the differentiation of other CNS cell types, and become critical regulators of CNS development. Here, we discuss exciting new work implicating microglia in a range of developmental processes, including regulation of cell number and spatial patterning of CNS cells, myelination, and formation and refinement of neural circuits. Furthermore, we review studies suggesting that these cellular functions result in the modulation of behavior, which has important implications for a variety of neurological disorders.

  13. Subcortical cytoskeleton periodicity throughout the nervous system

    PubMed Central

    D’Este, Elisa; Kamin, Dirk; Velte, Caroline; Göttfert, Fabian; Simons, Mikael; Hell, Stefan W.

    2016-01-01

    Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought. PMID:26947559

  14. Influence of thyroid in nervous system growth.

    PubMed

    Mussa, G C; Mussa, F; Bretto, R; Zambelli, M C; Silvestro, L

    2001-08-01

    Nervous system growth and differentiation are closely correlated with the presence of iodine and thyroid hormones in initial development stages. In the human species, encephalon maturation during the first quarter of pregnancy is affected according to recent studies by the transplacenta passage of maternal thyroid hormones while it depends on initial iodiothyronin secretion by the foetal gland after the 12th week of pregnancy. Thyroid hormone deficiency during nervous system development causes altered noble nervous cells, such as the pyramidal cortical and Purkinje cells, during glial cell proliferation and differentiation alike. Neurons present cell hypoplasia with reduced axon count, dendritic branching, synaptic spikes and interneuron connections. Oligodendrocytes decrease in number and average myelin content consequently drops. Biochemical studies on hypothyroid rats have demonstrated alterations to neuron intraplasmatic microtubule content and organisation, changed mitochondria number and arrangement and anomalies in T3 nuclear and citoplasmatic receptor maturation. Alterations to microtubules are probably responsible for involvement of the axon-dendrite system, and are the consequence of deficient thyroid hormone action on the mitochondria, the mitochondria enzymes and proteins associated with microtubules. Nuclear and citoplasmatic receptors have been identified and gene clonation studies have shown two families of nuclear receptors that include several sub-groups in their turn. A complex scheme of temporal and spatial expression of these receptors exists, so they probably contribute with one complementary function, although their physiological role differs. The action of thyroid hormones occurs by changing cell protein levels because of their regulation at the transcriptional or post-transcriptional level. Genes submitted to thyroid hormone control are either expressed by oligodendrytes, which are myelin protein coders or glial differentiation mediators, or

  15. Role of the Thyroid System in Myelination and Neural Connectivity.

    PubMed

    Calzà, Laura; Fernández, Mercedes; Giardino, Luciana

    2015-07-01

    The role of thyroid hormone on brain development is dramatically illustrated by "cretinism," a severe mental retardation due to iodine deficiency and maternal hypothyroidism during gestation. In the last decades, the molecular bases of the cellular action of thyroid hormone in the nervous tissue have been at least partially elucidated, and the emerged picture is much more complex than expected. In this article, the main mechanisms determining thyroid hormone availability, nuclear and membrane receptor occupancy and downstream action, gene expression, and nongenomic mechanism are reviewed, focusing on myelination and myelin turnover. PMID:26140723

  16. Connexin32 expression in central and peripheral nervous systems

    SciTech Connect

    Deschenes, S.M.; Scherer, S.S.; Fischbeck, K.H.

    1994-09-01

    Mutations have been identified in the gap junction gene, connexin32 (Cx32), in patients affected with the X-linked form of the demyelinating neuropathy, Charcot-Marie-Tooth disease (CMTX). Gap junctions composed of Cx32 are present and developmentally regulated in a wide variety of tissues. In peripheral nerve, our immunohistochemical analysis localized Cx32 to the noncompacted myelin of the paranodal regions and the Schmidt-Lantermann incisures, where previous studies describe gap junctions. In contrast to the location of Cx32 in peripheral nerve and the usual restriction of clinical manifestations to the peripheral nervous system (PNS) (abstract by Paulson describes an exception), preliminary studies show that Cx32 is present in the compacted myelin of the central nervous system (CNS), as demonstrated by radial staining through the myelin sheath of oligodendrocytes in rat spinal cord. Analysis of Cx32 expression in various regions of rat CNS during development shows that the amount of Cx32 mRNA and protein increases as myelination increases, a pattern observed for other myelin genes. Studies in the PNS provide additional evidence that Cx32 and myelin genes are coordinately regulated at the transcriptional level; Cx32 and peripheral myelin gene PMP-22 mRNAs are expressed in parallel following transient or permanent nerve injury. Differences in post-translational regulation of Cx32 in the CNS and PNS may be indicated by the presence of a faster migrating form of Cs32 in cerebrum versus peripheral nerve. Studies are currently underway to determine the unique role of Cx32 in peripheral nerve.

  17. Nervous system lyme disease.

    PubMed

    Halperin, John J

    2015-01-01

    Lyme disease, a multisystem spirochetal infection, continues to be the subject of considerable debate, but not controversy. Recent years have seen improvements in diagnostic tools, better understanding of pathophysiology, and increasing evidence of efficacy of standard treatment regimens. Nervous system involvement is particularly confusing to patients and many physicians. A rational approach based on objective findings can clarify the cause and dictate the best treatment of patients' difficulties. Diagnosis for all but the earliest cases rests on the combination of likely contact with infected Ixodes ticks and laboratory confirmation of exposure to the causative organism, Borrelia burgdorferi (two-tier serology, combining ELISA with a confirmatory Western blot). Treatment is generally with oral antimicrobials such as doxycycline. Parenteral regimens are usually necessary only for the most severe cases.

  18. Three-dimensional ultra-structures of myelin and the axons in the spinal cord: application of SEM with the osmium maceration method to the central nervous system in two mouse models.

    PubMed

    Nomura, Taichi; Bando, Yoshio; Bochimoto, Hiroki; Koga, Daisuke; Watanabe, Tsuyoshi; Yoshida, Shigetaka

    2013-03-01

    Axonal injury and demyelination are observed in demyelinating diseases such as multiple sclerosis. However, pathological changes that underlie these morphologies are not fully understood. We examined in vivo morphological changes using a new histological technique, scanning electron microscopy (SEM) with osmium maceration method to observe three-dimensional structures such as myelin and axons in the spinal cord. Myelin basic protein-deficient shiverer mice and mice with experimental autoimmune encephalomyelitis (EAE) were used to visualize how morphological changes in myelin and axons are induced by dysmyelination and demyelination. SEM revealed following morphological changes during dysmyelination of shiverer mice. First, enriched mitochondria and well-developed sER in axons were observed in shiverer, but not in wild-type mice. Second, the processes from some perinodal glial cells ran parallel to internodes of axons in addition to the process that covered the nodal region of the axon in shiverer mice. Last, this technique left myelin and axonal structures undisturbed. Moreover, SEM images showed clear variations in the ultrastructural abnormalities of myelin and axons in the white matter of the EAE spinal cord. This technique will be a powerful tool for identifying the mechanisms underlying the pathogenesis in demyelination.

  19. Cholesterol in myelin biogenesis and hypomyelinating disorders.

    PubMed

    Saher, Gesine; Stumpf, Sina Kristin

    2015-08-01

    The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids.

  20. Central Nervous System Lipoproteins

    PubMed Central

    Mahley, Robert W.

    2016-01-01

    ApoE on high-density lipoproteins is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS). Normally produced mostly by astrocytes, apoE is also produced under neuropathologic conditions by neurons. ApoE on high-density lipoproteins is critical in redistributing cholesterol and phospholipids for membrane repair and remodeling. The 3 main structural isoforms differ in their effectiveness. Unlike apoE2 and apoE3, apoE4 has markedly altered CNS metabolism, is associated with Alzheimer disease and other neurodegenerative disorders, and is expressed at lower levels in brain and cerebrospinal fluid. ApoE4-expressing cultured astrocytes and neurons have reduced cholesterol and phospholipid secretion, decreased lipid-binding capacity, and increased intracellular degradation. Two structural features are responsible for apoE4 dysfunction: domain interaction, in which arginine-61 interacts ionically with glutamic acid-255, and a less stable conformation than apoE3 and apoE2. Blocking domain interaction by gene targeting (replacing arginine-61 with threonine) or by small-molecule structure correctors increases CNS apoE4 levels and lipid-binding capacity and decreases intracellular degradation. Small molecules (drugs) that disrupt domain interaction, so-called structure correctors, could prevent the apoE4-associated neuropathology by blocking the formation of neurotoxic fragments. Understanding how to modulate CNS cholesterol transport and metabolism is providing important insights into CNS health and disease. PMID:27174096

  1. Nervous System Complexity Baffles Scientists.

    ERIC Educational Resources Information Center

    Fox, Jeffrey L.

    1982-01-01

    New research findings about how nerve cells transmit signals are forcing researchers to overhaul their simplistic ideas about the nervous system. Topics highlighted include the multiple role of peptides in the nervous system, receptor molecules, and molecules that form ion channels within membranes. (Author/JN)

  2. In vitro myelin formation using embryonic stem cells

    PubMed Central

    Kerman, Bilal E.; Kim, Hyung Joon; Padmanabhan, Krishnan; Mei, Arianna; Georges, Shereen; Joens, Matthew S.; Fitzpatrick, James A. J.; Jappelli, Roberto; Chandross, Karen J.; August, Paul; Gage, Fred H.

    2015-01-01

    Myelination in the central nervous system is the process by which oligodendrocytes form myelin sheaths around the axons of neurons. Myelination enables neurons to transmit information more quickly and more efficiently and allows for more complex brain functions; yet, remarkably, the underlying mechanism by which myelination occurs is still not fully understood. A reliable in vitro assay is essential to dissect oligodendrocyte and myelin biology. Hence, we developed a protocol to generate myelinating oligodendrocytes from mouse embryonic stem cells and established a myelin formation assay with embryonic stem cell-derived neurons in microfluidic devices. Myelin formation was quantified using a custom semi-automated method that is suitable for larger scale analysis. Finally, early myelination was followed in real time over several days and the results have led us to propose a new model for myelin formation. PMID:26015546

  3. In vitro myelin formation using embryonic stem cells.

    PubMed

    Kerman, Bilal E; Kim, Hyung Joon; Padmanabhan, Krishnan; Mei, Arianna; Georges, Shereen; Joens, Matthew S; Fitzpatrick, James A J; Jappelli, Roberto; Chandross, Karen J; August, Paul; Gage, Fred H

    2015-06-15

    Myelination in the central nervous system is the process by which oligodendrocytes form myelin sheaths around the axons of neurons. Myelination enables neurons to transmit information more quickly and more efficiently and allows for more complex brain functions; yet, remarkably, the underlying mechanism by which myelination occurs is still not fully understood. A reliable in vitro assay is essential to dissect oligodendrocyte and myelin biology. Hence, we developed a protocol to generate myelinating oligodendrocytes from mouse embryonic stem cells and established a myelin formation assay with embryonic stem cell-derived neurons in microfluidic devices. Myelin formation was quantified using a custom semi-automated method that is suitable for larger scale analysis. Finally, early myelination was followed in real time over several days and the results have led us to propose a new model for myelin formation.

  4. Myelin-specific proteins: a structurally diverse group of membrane-interacting molecules.

    PubMed

    Han, Huijong; Myllykoski, Matti; Ruskamo, Salla; Wang, Chaozhan; Kursula, Petri

    2013-01-01

    The myelin sheath is a multilayered membrane in the nervous system, which has unique biochemical properties. Myelin carries a set of specific high-abundance proteins, the structure and function of which are still poorly understood. The proteins of the myelin sheath are involved in a number of neurological diseases, including autoimmune diseases and inherited neuropathies. In this review, we briefly discuss the structural properties and functions of selected myelin-specific proteins (P0, myelin oligodendrocyte glycoprotein, myelin-associated glycoprotein, myelin basic protein, myelin-associated oligodendrocytic basic protein, P2, proteolipid protein, peripheral myelin protein of 22 kDa, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and periaxin); such properties include, for example, interactions with lipid bilayers and the presence of large intrinsically disordered regions in some myelin proteins. A detailed understanding of myelin protein structure and function at the molecular level will be required to fully grasp their physiological roles in the myelin sheath.

  5. Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases.

    PubMed

    Weil, Marie-Theres; Möbius, Wiebke; Winkler, Anne; Ruhwedel, Torben; Wrzos, Claudia; Romanelli, Elisa; Bennett, Jeffrey L; Enz, Lukas; Goebels, Norbert; Nave, Klaus-Armin; Kerschensteiner, Martin; Schaeren-Wiemers, Nicole; Stadelmann, Christine; Simons, Mikael

    2016-07-12

    Breakdown of myelin sheaths is a pathological hallmark of several autoimmune diseases of the nervous system. We employed autoantibody-mediated animal models of demyelinating diseases, including a rat model of neuromyelitis optica (NMO), to target myelin and found that myelin lamellae are broken down into vesicular structures at the innermost region of the myelin sheath. We demonstrated that myelin basic proteins (MBP), which form a polymer in between the myelin membrane layers, are targeted in these models. Elevation of intracellular Ca(2+) levels resulted in MBP network disassembly and myelin vesiculation. We propose that the aberrant phase transition of MBP molecules from their cohesive to soluble and non-adhesive state is a mechanism triggering myelin breakdown in NMO and possibly in other demyelinating diseases.

  6. Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases.

    PubMed

    Weil, Marie-Theres; Möbius, Wiebke; Winkler, Anne; Ruhwedel, Torben; Wrzos, Claudia; Romanelli, Elisa; Bennett, Jeffrey L; Enz, Lukas; Goebels, Norbert; Nave, Klaus-Armin; Kerschensteiner, Martin; Schaeren-Wiemers, Nicole; Stadelmann, Christine; Simons, Mikael

    2016-07-12

    Breakdown of myelin sheaths is a pathological hallmark of several autoimmune diseases of the nervous system. We employed autoantibody-mediated animal models of demyelinating diseases, including a rat model of neuromyelitis optica (NMO), to target myelin and found that myelin lamellae are broken down into vesicular structures at the innermost region of the myelin sheath. We demonstrated that myelin basic proteins (MBP), which form a polymer in between the myelin membrane layers, are targeted in these models. Elevation of intracellular Ca(2+) levels resulted in MBP network disassembly and myelin vesiculation. We propose that the aberrant phase transition of MBP molecules from their cohesive to soluble and non-adhesive state is a mechanism triggering myelin breakdown in NMO and possibly in other demyelinating diseases. PMID:27346352

  7. On the resemblance of synapse formation and CNS myelination.

    PubMed

    Almeida, R G; Lyons, D A

    2014-09-12

    The myelination of axons in the central nervous system (CNS) is essential for nervous system formation, function and health. CNS myelination continues well into adulthood, but not all axons become myelinated. Unlike the peripheral nervous system, where we know of numerous axon-glial signals required for myelination, we have a poor understanding of the nature or identity of such molecules that regulate which axons are myelinated in the CNS. Recent studies have started to elucidate cell behavior during myelination in vivo and indicate that the choice of which axons are myelinated is made prior to myelin sheath generation. Here we propose that interactions between axons and the exploratory processes of oligodendrocyte precursor cells (OPCs) lead to myelination and may be similar to those between dendrites and axons that prefigure and lead to synapse formation. Indeed axons and OPCs form synapses with striking resemblance to those of neurons, suggesting a similar mode of formation. We discuss families of molecules with specific functions at different stages of synapse formation and address studies that implicate the same factors during axon-OPC synapse formation and myelination. We also address the possibility that the function of such synapses might directly regulate the myelinating behavior of oligodendrocyte processes in vivo. In the future it may be of benefit to consider these similarities when taking a candidate-based approach to dissect mechanisms of CNS myelination.

  8. The cell biology of CNS myelination.

    PubMed

    Hughes, Ethan G; Appel, Bruce

    2016-08-01

    Myelination of axons in the central nervous system results from the remarkable ability of oligodendrocytes to wrap multiple axons with highly specialized membrane. Because myelin membrane grows as it ensheaths axons, cytoskeletal rearrangements that enable ensheathment must be coordinated with myelin production. Because the myelin sheaths of a single oligodendrocyte can differ in thickness and length, mechanisms that coordinate axon ensheathment with myelin growth likely operate within individual oligodendrocyte processes. Recent studies have revealed new information about how assembly and disassembly of actin filaments helps drive the leading edge of nascent myelin membrane around and along axons. Concurrently, other investigations have begun to uncover evidence of communication between axons and oligodendrocytes that can regulate myelin formation.

  9. Intravital assessment of myelin molecular order with polarimetric multiphoton microscopy

    PubMed Central

    Turcotte, Raphaël; Rutledge, Danette J.; Bélanger, Erik; Dill, Dorothy; Macklin, Wendy B.; Côté, Daniel C.

    2016-01-01

    Myelin plays an essential role in the nervous system and its disruption in diseases such as multiple sclerosis may lead to neuronal death, thus causing irreversible functional impairments. Understanding myelin biology is therefore of fundamental and clinical importance, but no tools currently exist to describe the fine spatial organization of myelin sheaths in vivo. Here we demonstrate intravital quantification of the myelin molecular structure using a microscopy method based on polarization-resolved coherent Raman scattering. Developmental myelination was imaged noninvasively in live zebrafish. Longitudinal imaging of individual axons revealed changes in myelin organization beyond the diffraction limit. Applied to promyelination drug screening, the method uniquely enabled the identification of focal myelin regions with differential architectures. These observations indicate that the study of myelin biology and the identification of therapeutic compounds will largely benefit from a method to quantify the myelin molecular organization in vivo. PMID:27538357

  10. Intravital assessment of myelin molecular order with polarimetric multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Turcotte, Raphaël; Rutledge, Danette J.; Bélanger, Erik; Dill, Dorothy; Macklin, Wendy B.; Côté, Daniel C.

    2016-08-01

    Myelin plays an essential role in the nervous system and its disruption in diseases such as multiple sclerosis may lead to neuronal death, thus causing irreversible functional impairments. Understanding myelin biology is therefore of fundamental and clinical importance, but no tools currently exist to describe the fine spatial organization of myelin sheaths in vivo. Here we demonstrate intravital quantification of the myelin molecular structure using a microscopy method based on polarization-resolved coherent Raman scattering. Developmental myelination was imaged noninvasively in live zebrafish. Longitudinal imaging of individual axons revealed changes in myelin organization beyond the diffraction limit. Applied to promyelination drug screening, the method uniquely enabled the identification of focal myelin regions with differential architectures. These observations indicate that the study of myelin biology and the identification of therapeutic compounds will largely benefit from a method to quantify the myelin molecular organization in vivo.

  11. Intravital assessment of myelin molecular order with polarimetric multiphoton microscopy.

    PubMed

    Turcotte, Raphaël; Rutledge, Danette J; Bélanger, Erik; Dill, Dorothy; Macklin, Wendy B; Côté, Daniel C

    2016-01-01

    Myelin plays an essential role in the nervous system and its disruption in diseases such as multiple sclerosis may lead to neuronal death, thus causing irreversible functional impairments. Understanding myelin biology is therefore of fundamental and clinical importance, but no tools currently exist to describe the fine spatial organization of myelin sheaths in vivo. Here we demonstrate intravital quantification of the myelin molecular structure using a microscopy method based on polarization-resolved coherent Raman scattering. Developmental myelination was imaged noninvasively in live zebrafish. Longitudinal imaging of individual axons revealed changes in myelin organization beyond the diffraction limit. Applied to promyelination drug screening, the method uniquely enabled the identification of focal myelin regions with differential architectures. These observations indicate that the study of myelin biology and the identification of therapeutic compounds will largely benefit from a method to quantify the myelin molecular organization in vivo. PMID:27538357

  12. Novel central nervous system drug delivery systems.

    PubMed

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

  13. Human nervous system function emulator.

    PubMed

    Frenger, P

    2000-01-01

    This paper describes a modular, extensible, open-systems design for a multiprocessor network which emulates the major functions of the human nervous system. Interchangeable hardware/software components, a socketed software bus with plug-and-play capability and self diagnostics are included. The computer hardware is based on IEEE P996.1 bus cards. Its operating system utilizes IEEE 1275 standard software. Object oriented design techniques and programming are featured. A machine-independent high level script-based command language was created for this project. Neural anatomical structures which were emulated include the cortex, brainstem, cerebellum, spinal cord, autonomic and peripheral nervous systems. Motor, sensory, autoregulatory, and higher cognitive artificial intelligence, behavioral and emotional functions are provided. The author discusses how he has interfaced this emulator to machine vision, speech recognition/speech synthesis, an artificial neural network and a dexterous hand to form an android robotic platform. PMID:10834247

  14. Histology of the central nervous system.

    PubMed

    Garman, Robert H

    2011-01-01

    The intent of this article is to assist pathologists inexperienced in examining central nervous system (CNS) sections to recognize normal and abnormal cell types as well as some common artifacts. Dark neurons are the most common histologic artifact but, with experience, can readily be distinguished from degenerating (eosinophilic) neurons. Neuron degeneration stains can be useful in lowering the threshold for detecting neuron degeneration as well as for revealing degeneration within populations of neurons that are too small to show the associated eosinophilic cytoplasmic alteration within H&E-stained sections. Neuron degeneration may also be identified by the presence of associated macroglial and microglial reactions. Knowledge of the distribution of astrocyte cytoplasmic processes is helpful in determining that certain patterns of treatment-related neuropil vacuolation (as well as some artifacts) represent swelling of these processes. On the other hand, vacuoles with different distribution patterns may represent alterations of the myelin sheath. Because brains are typically undersampled for microscopic evaluation, many pathologists are unfamiliar with the circumventricuar organs (CVOs) that represent normal brain structures but are often mistaken for lesions. Therefore, the six CVOs found in the brain are also illustrated in this article.

  15. Clinical implications of thyroid hormones effects on nervous system development.

    PubMed

    Carreón-Rodríguez, Alfonso; Pérez-Martínez, Leonor

    2012-03-01

    Thyroid hormones have an important role throughout prenatal and postnatal nervous system development. They are involved in several processes such as neurogenesis, gliogenesis, myelination, synaptogenesis, etc., as shown in many cases of deficiency like congenital hypothyroidism or hypothyroxinemia. Those pathologies if untreated could lead to severe damages in cognitive, motor, neudoendocrine functions among other effects. Some could be reversed after adequate supplementation of thyroid hormones at birth, however there are other cellular processes highly sensitive to low levels of thyroid hormones and lasting a limited period of time during which if thyroid hormone action is lacking or deficient, the functional and structural damages would produce permanent defects. PMID:22523832

  16. Extracellular vesicles round off communication in the nervous system

    PubMed Central

    Budnik, Vivian; Ruiz-Cañada, Catalina; Wendler, Franz

    2016-01-01

    Functional neural competence and integrity require interactive exchanges among sensory and motor neurons, interneurons and glial cells. Recent studies have attributed some of the tasks needed for these exchanges to extracellular vesicles (such as exosomes and microvesicles), which are most prominently involved in shuttling reciprocal signals between myelinating glia and neurons, thus promoting neuronal survival, the immune response mediated by microglia, and synapse assembly and plasticity. Such vesicles have also been identified as important factors in the spread of neurodegenerative disorders and brain cancer. These extracellular vesicle functions add a previously unrecognized level of complexity to transcellular interactions within the nervous system. PMID:26891626

  17. Autoimmune T cell responses in the central nervous system

    PubMed Central

    Goverman, Joan

    2010-01-01

    Autoreactive T cell responses have a crucial role in central nervous system (CNS) diseases such as multiple sclerosis. Recent data indicate that CNS autoimmunity can be mediated by two distinct lineages of CD4+ T cells that are defined by the production of either interferon-γ or interleukin-17. The activity of these CD4+ T cell subsets within the CNS influences the pathology and clinical course of disease. New animal models show that myelin-specific CD8+ T cells can also mediate CNS autoimmunity. This Review focuses on recent progress in delineating the pathogenic mechanisms, regulation and interplay between these different T cell subsets in CNS autoimmunity. PMID:19444307

  18. Maturation of the Central Nervous System as Related to Communication and Cognitive Development.

    ERIC Educational Resources Information Center

    Hallett, Terry; Proctor, Adele

    1996-01-01

    Major events in the maturation of the central nervous system (CNS) are reviewed relative to milestones for communication, speech, language, and cognition. Early insults to the CNS and their neuropsychological consequences are discussed. The role of patterns of myelination and dendritic branching to evolving stages of language and cognition are…

  19. [The role of metalloprotease in pathogenesis of nervous system diseases].

    PubMed

    Mirowska, D; Członkowska, A

    2001-01-01

    Matrix Metalloproteases (MMPs) comprise a big family of proteolytic enzymes secreted into extracellular matrix and involved in remodelling of many tissues. The MMPs' activity is regulated on many levels. It is also determined by specific inhibitors known as tissue inhibitors of metalloproteases (TIMPs). Several studies revealed that MMPs have a role not only in physiological processes but also in pathophysiology of nervous system diseases, such as multiplex sclerosis, Guillan-Barré syndrome and strokes. Concerning demyelination MMPs are responsible for degradation of myelin components and facilitation of immune cells migration into inflammatory sites by degrading vascular basement membrane. We still investigate substances with positive clinical effect on the nervous system diseases due to MMPs inactivation.

  20. The history of myelin.

    PubMed

    Boullerne, Anne Isabelle

    2016-09-01

    Andreas Vesalius is attributed the discovery of white matter in the 16th century but van Leeuwenhoek is arguably the first to have observed myelinated fibers in 1717. A globular myelin theory followed, claiming all elements of the nervous system except for Fontana's primitive cylinder with outer sheath in 1781. Remak's axon revolution in 1836 relegated myelin to the unknown. Ehrenberg described nerve tubes with double borders in 1833, and Schwann with nuclei in 1839, but the medullary sheath acquired its name of myelin, coined by Virchow, only in 1854. Thanks to Schultze's osmium specific staining in 1865, myelin designates the structure known today. The origin of myelin though was baffling. Only after Ranvier discovered a periodic segmentation, which came to us as nodes of Ranvier, did he venture suggesting in 1872 that the nerve internode was a fatty cell secreting myelin in cytoplasm. Ranvier's hypothesis was met with high skepticism, because nobody could see the cytoplasm, and the term Schwann cell very slowly emerged into the vocabulary with von Lenhossék in 1895. When Cajal finally admitted the concept of Schwann cell internode in 1912, he still firmly believed myelin was secreted by the axon. Del Río-Hortega re-discovered oligodendrocytes in 1919 (after Robertson in 1899) and named them oligodendroglia in 1921, thereby antagonizing Cajal for discovering a second cell type in his invisible third element. Penfield had to come to del Río-Hortega's rescue in 1924 for oligodendrocytes to be accepted. They jointly hypothesized myelin could be made by oligodendrocytes, considered the central equivalent of Schwann cells. Meanwhile myelin birefringence properties observed by Klebs in 1865 then Schmidt in 1924 confirmed its high fatty content, ascertained by biochemistry by Thudichum in 1884. The 20th century saw X-ray diffraction developed by Schmitt, who discovered in 1935 the crystal-like organization of this most peculiar structure, and devised the g

  1. The Nervous System and Gastrointestinal Function

    ERIC Educational Resources Information Center

    Altaf, Muhammad A.; Sood, Manu R.

    2008-01-01

    The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia,…

  2. CFTR-deficient pigs display peripheral nervous system defects at birth

    PubMed Central

    Reznikov, Leah R.; Dong, Qian; Chen, Jeng-Haur; Moninger, Thomas O.; Park, Jung Min; Zhang, Yuzhou; Hildebrand, Michael S.; Smith, Richard J. H.; Randak, Christoph O.; Stoltz, David A.; Welsh, Michael J.

    2013-01-01

    Peripheral nervous system abnormalities, including neuropathy, have been reported in people with cystic fibrosis. These abnormalities have largely been attributed to secondary manifestations of the disease. We tested the hypothesis that disruption of the cystic fibrosis transmembrane conductance regulator (CFTR) gene directly influences nervous system function by studying newborn CFTR−/− pigs. We discovered CFTR expression and activity in Schwann cells, and loss of CFTR caused ultrastructural myelin sheath abnormalities similar to those in known neuropathies. Consistent with neuropathic changes, we found increased transcripts for myelin protein zero, a gene that, when mutated, can cause axonal and/or demyelinating neuropathy. In addition, axon density was reduced and conduction velocities of the trigeminal and sciatic nerves were decreased. Moreover, in vivo auditory brainstem evoked potentials revealed delayed conduction of the vestibulocochlear nerve. Our data suggest that loss of CFTR directly alters Schwann cell function and that some nervous system defects in people with cystic fibrosis are likely primary. PMID:23382208

  3. Glucocorticoids and nervous system plasticity.

    PubMed

    Madalena, Kathryn M; Lerch, Jessica K

    2016-01-01

    Glucocorticoid and glucocorticoid receptor (GC/GR) interactions alter numerous aspects of neuronal function. These consequences (e.g., anti-inflammatory vs. pro-inflammatory) can vary depending on the duration of GC exposure or central nervous system (CNS) injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing. PMID:26981074

  4. Central Nervous System Device Infections.

    PubMed

    Hasbun, Rodrigo

    2016-11-01

    Nosocomial meningitis can occur in association with central nervous system (CNS) devices such as cerebrospinal shunts or drains, intrathecal pumps, and deep brain stimulators and carry substantial morbidity and mortality. Diagnosing and treating these infections may be challenging to physicians as cerebrospinal fluid cultures may be negative due to previous antibiotic therapy and cerebrospinal abnormalities may be secondary to the primary neurosurgical issue that prompted the placement of the CNS device (e.g., "chemical meningitis" due to intracranial hemorrhage). Besides antibiotic therapy given intravenously and sometimes intrathecally, removal of the device with repeat cultures prior to re-implantation is key in achieving successful outcomes. PMID:27686676

  5. Lavender and the Nervous System

    PubMed Central

    Koulivand, Peir Hossein; Khaleghi Ghadiri, Maryam; Gorji, Ali

    2013-01-01

    Lavender is traditionally alleged to have a variety of therapeutic and curative properties, ranging from inducing relaxation to treating parasitic infections, burns, insect bites, and spasm. There is growing evidence suggesting that lavender oil may be an effective medicament in treatment of several neurological disorders. Several animal and human investigations suggest anxiolytic, mood stabilizer, sedative, analgesic, and anticonvulsive and neuroprotective properties for lavender. These studies raised the possibility of revival of lavender therapeutic efficacy in neurological disorders. In this paper, a survey on current experimental and clinical state of knowledge about the effect of lavender on the nervous system is given. PMID:23573142

  6. Glucocorticoids and nervous system plasticity

    PubMed Central

    Madalena, Kathryn M.; Lerch, Jessica K.

    2016-01-01

    Glucocorticoid and glucocorticoid receptor (GC/GR) interactions alter numerous aspects of neuronal function. These consequences (e.g., anti-inflammatory vs. pro-inflammatory) can vary depending on the duration of GC exposure or central nervous system (CNS) injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing. PMID:26981074

  7. α-Synuclein-induced myelination deficit defines a novel interventional target for multiple system atrophy.

    PubMed

    Ettle, Benjamin; Kerman, Bilal E; Valera, Elvira; Gillmann, Clarissa; Schlachetzki, Johannes C M; Reiprich, Simone; Büttner, Christian; Ekici, Arif B; Reis, André; Wegner, Michael; Bäuerle, Tobias; Riemenschneider, Markus J; Masliah, Eliezer; Gage, Fred H; Winkler, Jürgen

    2016-07-01

    Multiple system atrophy (MSA) is a rare atypical parkinsonian disorder characterized by a rapidly progressing clinical course and at present without any efficient therapy. Neuropathologically, myelin loss and neurodegeneration are associated with α-synuclein accumulation in oligodendrocytes, but underlying pathomechanisms are poorly understood. Here, we analyzed the impact of oligodendrocytic α-synuclein on the formation of myelin sheaths to define a potential interventional target for MSA. Post-mortem analyses of MSA patients and controls were performed to quantify myelin and oligodendrocyte numbers. As pre-clinical models, we used transgenic MSA mice, a myelinating stem cell-derived oligodendrocyte-neuron co-culture, and primary oligodendrocytes to determine functional consequences of oligodendrocytic α-synuclein overexpression on myelination. We detected myelin loss accompanied by preserved or even increased numbers of oligodendrocytes in post-mortem MSA brains or transgenic mouse forebrains, respectively, indicating an oligodendrocytic dysfunction in myelin formation. Corroborating this observation, overexpression of α-synuclein in primary and stem cell-derived oligodendrocytes severely impaired myelin formation, defining a novel α-synuclein-linked pathomechanism in MSA. We used the pro-myelinating activity of the muscarinic acetylcholine receptor antagonist benztropine to analyze the reversibility of the myelination deficit. Transcriptome profiling of primary pre-myelinating oligodendrocytes demonstrated that benztropine readjusts myelination-related processes such as cholesterol and membrane biogenesis, being compromised by oligodendrocytic α-synuclein. Additionally, benztropine restored the α-synuclein-induced myelination deficit of stem cell-derived oligodendrocytes. Strikingly, benztropine also ameliorated the myelin deficit in transgenic MSA mice, resulting in a prevention of neuronal cell loss. In conclusion, this study defines the

  8. Aquaporin Biology and Nervous System

    PubMed Central

    Barbara, Buffoli

    2010-01-01

    Our understanding of the movement of water through cell membranes has been greatly advanced by the discovery of a family of water-specific, membrane-channel proteins: the Aquaporins (AQPs). These proteins are present in organisms at all levels of life, and their unique permeability characteristics and distribution in numerous tissues indicate diverse roles in the regulation of water homeostasis. Phenotype analysis of AQP knock-out mice has confirmed the predicted role of AQPs in osmotically driven transepithelial fluid transport, as occurs in the urinary concentrating mechanism and glandular fluid secretion. Regarding their expression in nervous system, there are evidences suggesting that AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in cerebrospinal fluid formation, neuronal signal transduction and information processing. Moreover, a number of recent studies have revealed the importance of mammalian AQPs in both physiological and pathophysiological mechanisms and have suggested that pharmacological modulation of AQP expression and activity may provide new tools for the treatment of variety of human disorders in which water and small solute transport may be involved. For all the AQPs, new contributions to physiological functions are likely to be discovered with ongoing work in this rapidly expanding field of research. PMID:21119880

  9. Testing the autonomic nervous system.

    PubMed

    Freeman, Roy; Chapleau, Mark W

    2013-01-01

    Autonomic testing is used to define the role of the autonomic nervous system in diverse clinical and research settings. Because most of the autonomic nervous system is inaccessible to direct physiological testing, in the clinical setting the most widely used techniques entail the assessment of an end-organ response to a physiological provocation. The noninvasive measures of cardiovascular parasympathetic function involve the assessment of heart rate variability while the measures of cardiovascular sympathetic function assess the blood pressure response to physiological stimuli. Tilt-table testing, with or without pharmacological provocation, has become an important tool in the assessment of a predisposition to neurally mediated (vasovagal) syncope, the postural tachycardia syndrome, and orthostatic hypotension. Distal, postganglionic, sympathetic cholinergic (sudomotor) function may be evaluated by provoking axon reflex mediated sweating, e.g., the quantitative sudomotor axon reflex (QSART) or the quantitative direct and indirect axon reflex (QDIRT). The thermoregulatory sweat test provides a nonlocalizing measure of global pre- and postganglionic sudomotor function. Frequency domain analyses of heart rate and blood pressure variability, microneurography, and baroreflex assessment are currently research tools but may find a place in the clinical assessment of autonomic function in the future. PMID:23931777

  10. Hypersensitivity Responses in the Central Nervous System

    PubMed Central

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen; Berg, Carsten Tue; Owens, Trevor

    2015-01-01

    Immune-mediated tissue damage or hypersensitivity can be mediated by autospecific IgG antibodies. Pathology results from activation of complement, and antibody-dependent cellular cytotoxicity, mediated by inflammatory effector leukocytes include macrophages, natural killer cells, and granulocytes. Antibodies and complement have been associated to demyelinating pathology in multiple sclerosis (MS) lesions, where macrophages predominate among infiltrating myeloid cells. Serum-derived autoantibodies with predominant specificity for the astrocyte water channel aquaporin-4 (AQP4) are implicated as inducers of pathology in neuromyelitis optica (NMO), a central nervous system (CNS) demyelinating disease where activated neutrophils infiltrate, unlike in MS. The most widely used model for MS, experimental autoimmune encephalomyelitis, is an autoantigen-immunized disease that can be transferred to naive animals with CD4+ T cells, but not with antibodies. By contrast, NMO-like astrocyte and myelin pathology can be transferred to mice with AQP4–IgG from NMO patients. This is dependent on complement, and does not require T cells. Consistent with clinical observations that interferon-beta is ineffective as a therapy for NMO, NMO-like pathology is significantly reduced in mice lacking the Type I IFN receptor. In MS, there is evidence for intrathecal synthesis of antibodies as well as blood–brain barrier (BBB) breakdown, whereas in NMO, IgG accesses the CNS from blood. Transfer models involve either direct injection of antibody and complement to the CNS, or experimental manipulations to induce BBB breakdown. We here review studies in MS and NMO that elucidate roles for IgG and complement in the induction of BBB breakdown, astrocytopathy, and demyelinating pathology. These studies point to significance of T-independent effector mechanisms in neuroinflammation. PMID:26500654

  11. IκB kinase 2 determines oligodendrocyte loss by non-cell-autonomous activation of NF-κB in the central nervous system

    PubMed Central

    Raasch, Jenni; Zeller, Nicolas; van Loo, Geert; Merkler, Doron; Mildner, Alexander; Erny, Daniel; Knobeloch, Klaus-Peter; Bethea, John R.; Waisman, Ari; Knust, Markus; Del Turco, Domenico; Deller, Thomas; Blank, Thomas; Priller, Josef; Brück, Wolfgang

    2011-01-01

    The IκB kinase complex induces nuclear factor kappa B activation and has recently been recognized as a key player of autoimmunity in the central nervous system. Notably, IκB kinase/nuclear factor kappa B signalling regulates peripheral myelin formation by Schwann cells, however, its role in myelin formation in the central nervous system during health and disease is largely unknown. Surprisingly, we found that brain-specific IκB kinase 2 expression is dispensable for proper myelin assembly and repair in the central nervous system, but instead plays a fundamental role for the loss of myelin in the cuprizone model. During toxic demyelination, inhibition of nuclear factor kappa B activation by conditional ablation of IκB kinase 2 resulted in strong preservation of central nervous system myelin, reduced expression of proinflammatory mediators and a significantly attenuated glial response. Importantly, IκB kinase 2 depletion in astrocytes, but not in oligodendrocytes, was sufficient to protect mice from myelin loss. Our results reveal a crucial role of glial cell-specific IκB kinase 2/nuclear factor kappa B signalling for oligodendrocyte damage during toxic demyelination. Thus, therapies targeting IκB kinase 2 function in non-neuronal cells may represent a promising strategy for the treatment of distinct demyelinating central nervous system diseases. PMID:21310728

  12. Paranodal reorganization results in the depletion of transverse bands in the aged central nervous system

    PubMed Central

    Shepherd, Mark N.; Pomicter, Anthony D.; Velazco, Cristine S.; Henderson, Scott C.; Dupree, Jeffrey L.

    2012-01-01

    Paranodal axo-glial junctional complexes anchor the myelin sheath to the axon and breakdown of these complexes presumably facilitates demyelination. Myelin deterioration is also prominent in the aging central nervous system (CNS); however, the stability of the paranodal complexes in the aged CNS has not been examined. Here, we show that transverse bands, prominent components of paranodal junctions, are significantly reduced in the aged CNS; however, the number of paired clusters of both myelin and axonal paranodal proteins is not altered. Ultrastructural analyses also reveal that thicker myelin sheaths display a “piling” of paranodal loops, the cytoplasm-containing sacs that demarcate the paranode. Loops involved in piling are observed throughout the paranode and are not limited to loops positioned in either the nodal- or juxtanodal-most regions. Here, we propose that as myelination continues, previously anchored loops lose their transverse bands and recede away from the axolemma. Newly juxtaposed loops then lose their transverse bands, move laterally to fill in the gap left by the receded loops and finally reform their transverse bands. This paranodal reorganization results in conservation of paranodal length, which may be important in maintaining ion channel spacing and axonal function. Furthermore, we propose that transverse band reformation is less efficient in the aged CNS, resulting in the significant reduction of these junctional components. Although demyelination was not observed, we propose that loss of transverse bands facilitates myelin degeneration and may predispose the aged CNS to a poorer prognosis following a secondary insult. PMID:20888080

  13. Paranodal reorganization results in the depletion of transverse bands in the aged central nervous system.

    PubMed

    Shepherd, Mark N; Pomicter, Anthony D; Velazco, Cristine S; Henderson, Scott C; Dupree, Jeffrey L

    2012-01-01

    Paranodal axo-glial junctional complexes anchor the myelin sheath to the axon and breakdown of these complexes presumably facilitates demyelination. Myelin deterioration is also prominent in the aging central nervous system (CNS); however, the stability of the paranodal complexes in the aged CNS has not been examined. Here, we show that transverse bands, prominent components of paranodal junctions, are significantly reduced in the aged CNS; however, the number of paired clusters of both myelin and axonal paranodal proteins is not altered. Ultrastructural analyses also reveal that thicker myelin sheaths display a "piling" of paranodal loops, the cytoplasm-containing sacs that demarcate the paranode. Loops involved in piling are observed throughout the paranode and are not limited to loops positioned in either the nodal- or juxtanodal-most regions. Here, we propose that as myelination continues, previously anchored loops lose their transverse bands and recede away from the axolemma. Newly juxtaposed loops then lose their transverse bands, move laterally to fill in the gap left by the receded loops and finally reform their transverse bands. This paranodal reorganization results in conservation of paranodal length, which may be important in maintaining ion channel spacing and axonal function. Furthermore, we propose that transverse band reformation is less efficient in the aged CNS, resulting in the significant reduction of these junctional components. Although demyelination was not observed, we propose that loss of transverse bands facilitates myelin degeneration and may predispose the aged CNS to a poorer prognosis following a secondary insult. PMID:20888080

  14. Autonomic nervous system and immune system interactions.

    PubMed

    Kenney, M J; Ganta, C K

    2014-07-01

    The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological, and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines, and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease

  15. Biophysical studies on the structure and function of molecules from the vertebrate myelin sheath

    NASA Astrophysics Data System (ADS)

    Wang, Chaozhan; Myllykoski, Matti; Kursula, Petri

    2010-11-01

    The myelin sheath is a crucial structure for the proper functioning of the vertebrate nervous system. We employ diverse methods to study the structure, function, and dynamics of the molecules specifically present in myelin. Eventually, we hope to better understand the details of the tightly packed myelin structure and the etiology of myelin-related diseases. The paper will provide background into the molecular structure of myelin, and recent results from our laboratory, dealing with the structure and function of selected myelin proteins, will be highlighted.

  16. Gross anatomy and development of the peripheral nervous system.

    PubMed

    Catala, Martin; Kubis, Nathalie

    2013-01-01

    The nervous system is divided into the central nervous system (CNS) composed of the brain, the brainstem, the cerebellum, and the spinal cord and the peripheral nervous system (PNS) made up of the different nerves arising from the CNS. The PNS is divided into the cranial nerves III to XII supplying the head and the spinal nerves that supply the upper and lower limbs. The general anatomy of the PNS is organized according to the arrangement of the fibers along the rostro-caudal axis. The control of the development of the PNS has been unravelled during the last 30 years. Motor nerves arise from the ventral neural tube. This ventralization is induced by morphogenetic molecules such as sonic hedgehog. In contrast, the sensory elements of the PNS arise from a specific population of cells originating from the roof of the neural tube, namely the neural crest. These cells give rise to the neurons of the dorsal root ganglia, the autonomic ganglia and the paraganglia including the adrenergic neurons of the adrenals. Furthermore, the supportive glial Schwann cells of the PNS originate from the neural crest cells. Growth factors as well as myelinating proteins are involved in the development of the PNS.

  17. Structural and dynamical properties of reconstituted myelin sheaths in the presence of myelin proteins MBP and P2 studied by neutron scattering.

    PubMed

    Knoll, Wiebke; Peters, Judith; Kursula, Petri; Gerelli, Yuri; Ollivier, Jacques; Demé, Bruno; Telling, Mark; Kemner, Ewout; Natali, Francesca

    2014-01-21

    The myelin sheath is a tightly packed, multilayered membrane structure wrapped around selected nerve axons in the central and the peripheral nervous system. Because of its electrical insulation of the axons, which allows fast, saltatory nerve impulse conduction, myelin is crucial for the proper functioning of the vertebrate nervous system. A subset of myelin-specific proteins is well-defined, but their influence on membrane dynamics, i.e. myelin stability, has not yet been explored in detail. We investigated the structure and the dynamics of reconstituted myelin membranes on a pico- to nanosecond timescale, influenced by myelin basic protein (MBP) and myelin protein 2 (P2), using neutron diffraction and quasi-elastic neutron scattering. A model for the scattering function describing molecular lipid motions is suggested. Although dynamical properties are not affected significantly by MBP and P2 proteins, they act in a highly synergistic manner influencing the membrane structure.

  18. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves.

    PubMed

    Gomez-Sanchez, Jose A; Carty, Lucy; Iruarrizaga-Lejarreta, Marta; Palomo-Irigoyen, Marta; Varela-Rey, Marta; Griffith, Megan; Hantke, Janina; Macias-Camara, Nuria; Azkargorta, Mikel; Aurrekoetxea, Igor; De Juan, Virginia Gutiérrez; Jefferies, Harold B J; Aspichueta, Patricia; Elortza, Félix; Aransay, Ana M; Martínez-Chantar, María L; Baas, Frank; Mato, José M; Mirsky, Rhona; Woodhoo, Ashwin; Jessen, Kristján R

    2015-07-01

    Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell-mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury. We also present evidence that myelinophagy is defective in the injured central nervous system. These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease.

  19. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves

    PubMed Central

    Gomez-Sanchez, Jose A.; Carty, Lucy; Iruarrizaga-Lejarreta, Marta; Palomo-Irigoyen, Marta; Varela-Rey, Marta; Griffith, Megan; Hantke, Janina; Macias-Camara, Nuria; Azkargorta, Mikel; Aurrekoetxea, Igor; De Juan, Virginia Gutiérrez; Jefferies, Harold B.J.; Aspichueta, Patricia; Elortza, Félix; Aransay, Ana M.; Martínez-Chantar, María L.; Baas, Frank; Mato, José M.; Mirsky, Rhona

    2015-01-01

    Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell–mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury. We also present evidence that myelinophagy is defective in the injured central nervous system. These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease. PMID:26150392

  20. Sympathetic nervous system and spaceflight

    NASA Astrophysics Data System (ADS)

    Cooke, William H.; Convertino, Victor A.

    2007-02-01

    Purpose: Orthostatic stability on Earth is maintained through sympathetic nerve activation sufficient to increase peripheral vascular resistance and defend against reductions of blood pressure. Orthostatic instability in astronauts upon return from space missions has been linked to blunted vascular resistance responses to standing, introducing the possibility that spaceflight alters normal function between sympathetic efferent traffic and vascular reactivity. Methods: We evaluated published results of spaceflight and relevant ground-based microgravity simulations in an effort to determine responses of the sympathetic nervous system and consequences for orthostatic stability. Results: Direct microneurographic recordings from humans in space revealed that sympathetic nerve activity is increased and preserved in the upright posture after return to Earth (STS-90). However, none of the astronauts studied during STS-90 presented with presyncope postflight, leaving unanswered the question of whether postflight orthostatic intolerance is associated with blunted sympathetic nerve responses or inadequate translation into vascular resistance. Conclusions: There is little evidence to support the concept that spaceflight induces fundamental sympathetic neuroplasticity. The available data seem to support the hypothesis that regardless of whether or not sympathetic traffic is altered during flight, astronauts return with reduced blood volumes and consequent heightened baseline sympathetic activity. Because of this, the ability to withstand an orthostatic challenge postflight is directly proportional to an astronaut's maximal sympathetic activation capacity and remaining sympathetic reserve.

  1. Axon-glia interaction and membrane traffic in myelin formation

    PubMed Central

    White, Robin; Krämer-Albers, Eva-Maria

    2014-01-01

    In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialized glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarization followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasizing the central role of the Src-family kinase Fyn during central nervous system (CNS) myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of proteolipid protein (PLP) transport by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases. PMID:24431989

  2. Oligodendrocyte precursors migrate along vasculature in the developing nervous system.

    PubMed

    Tsai, Hui-Hsin; Niu, Jianqin; Munji, Roeben; Davalos, Dimitrios; Chang, Junlei; Zhang, Haijing; Tien, An-Chi; Kuo, Calvin J; Chan, Jonah R; Daneman, Richard; Fancy, Stephen P J

    2016-01-22

    Oligodendrocytes myelinate axons in the central nervous system and develop from oligodendrocyte precursor cells (OPCs) that must first migrate extensively during brain and spinal cord development. We show that OPCs require the vasculature as a physical substrate for migration. We observed that OPCs of the embryonic mouse brain and spinal cord, as well as the human cortex, emerge from progenitor domains and associate with the abluminal endothelial surface of nearby blood vessels. Migrating OPCs crawl along and jump between vessels. OPC migration in vivo was disrupted in mice with defective vascular architecture but was normal in mice lacking pericytes. Thus, physical interactions with the vascular endothelium are required for OPC migration. We identify Wnt-Cxcr4 (chemokine receptor 4) signaling in regulation of OPC-endothelial interactions and propose that this signaling coordinates OPC migration with differentiation. PMID:26798014

  3. Oligodendrocyte precursors migrate along vasculature in the developing nervous system.

    PubMed

    Tsai, Hui-Hsin; Niu, Jianqin; Munji, Roeben; Davalos, Dimitrios; Chang, Junlei; Zhang, Haijing; Tien, An-Chi; Kuo, Calvin J; Chan, Jonah R; Daneman, Richard; Fancy, Stephen P J

    2016-01-22

    Oligodendrocytes myelinate axons in the central nervous system and develop from oligodendrocyte precursor cells (OPCs) that must first migrate extensively during brain and spinal cord development. We show that OPCs require the vasculature as a physical substrate for migration. We observed that OPCs of the embryonic mouse brain and spinal cord, as well as the human cortex, emerge from progenitor domains and associate with the abluminal endothelial surface of nearby blood vessels. Migrating OPCs crawl along and jump between vessels. OPC migration in vivo was disrupted in mice with defective vascular architecture but was normal in mice lacking pericytes. Thus, physical interactions with the vascular endothelium are required for OPC migration. We identify Wnt-Cxcr4 (chemokine receptor 4) signaling in regulation of OPC-endothelial interactions and propose that this signaling coordinates OPC migration with differentiation.

  4. Immunocytochemical Localization of Monoamine Oxidase Type B in Rat's Peripheral Nervous System.

    PubMed

    Chen, Qiang; Xu, Yang; Zhang, Hui; Tan, Xiao; Liu, Shu Hui; Yan, Fen

    2015-11-01

    Immunohistochemistry is used to investigate subcellular localization of monoamine oxidase type B (MAOB) in the axon of the rat's peripheral nervous system. Through light and electron microscopy, the presence of MAOB-immunoreactive structures in the propria lamina of tongue and on the outer membranes of mitochondria in both myelinated and unmyelinated axons can be detected. As a result, MAOB may potentially play a crucial role in the axons of the rat's peripheral nervous system and may be closely associated with both axonal transport and nerve conduction.

  5. Myelin Under Stress

    PubMed Central

    D’Antonio, Maurizio; Feltri, M. Laura; Wrabetz, Lawrence

    2011-01-01

    The capacity to fold proteins properly is fundamental for cell survival. Secreted and transmembrane proteins are synthesized in the endoplasmic reticulum (ER), an organelle that has the ability to discriminate between native and non-native proteins, in a process called protein quality control. When folding is not properly achieved, misfolded proteins can accumulate. The terminally misfolded proteins are typically retro-translocated into the cytoplasm for degradation by the proteasome, in a process known as endoplasmic reticulum associated degradation. However, if the degradation is insufficient, accumulation of abnormal proteins in the ER activates the unfolded protein response (UPR), a complex set of new signals aimed to further reduce the load of abnormal protein in the ER. Massive synthesis of myelin lipids and proteins is necessary to support myelinogenesis. Not surprisingly, therefore, ER stress (including the UPR), the proteasome and autophagy (lysosomes), have been implicated in myelin disorders, such as Pelizaeus-Merzbacher disease and vanishing white matter disease in the central nervous system and Charcot-Marie-Tooth neuropathies in the peripheral nervous system. Here we will discuss recent evidence supporting an important role for ER stress in myelin disorders. PMID:19330777

  6. Characterization of the shark myelin Po protein.

    PubMed

    Rotenstein, L; Herath, K; Gould, R M; de Bellard, M E

    2008-01-01

    Myelin, the insulating sheath made by extensive plasma membrane wrapping, is dependent on the presence of highly adhesive molecules that keep the two sides of the membrane in tight contact. The Po glycoprotein (Po) is the major component of the peripheral nervous system (PNS) myelin of mammals. The exact role that Po protein has played in the evolution of myelin is still unclear, but several phylogenetic observations suggest that it is a crucial component in the development of myelin as a multi-lamellar membrane structure. Sharks, which appeared in the fossil record about 400 million years ago, are the first fully myelinated organisms. In this study we investigated the expression pattern of shark myelin Po to suggest a way it might have played a role in the evolution of myelin in the central nervous system. We found that sharks have more than two isoforms (32, 28 and 25 kD), and that some of these might not be fully functional because they lack the domains known for Po homophilic adhesion.

  7. The sympathetic nervous system and heart failure.

    PubMed

    Zhang, David Y; Anderson, Allen S

    2014-02-01

    Heart failure (HF) is a syndrome characterized by upregulation of the sympathetic nervous system and abnormal responsiveness of the parasympathetic nervous system. Studies in the 1980s and 1990s demonstrated that inhibition of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors improved symptoms and mortality in HF resulting from systolic dysfunction, thus providing a framework to consider the use of β-blockers for HF therapy, contrary to the prevailing wisdom of the time. Against this backdrop, this article reviews the contemporary understanding of the sympathetic nervous system and the failing heart.

  8. Extracellular Matrix: Functions in the Nervous System

    PubMed Central

    Barros, Claudia S.; Franco, Santos J.; Müller, Ulrich

    2011-01-01

    An astonishing number of extracellular matrix glycoproteins are expressed in dynamic patterns in the developing and adult nervous system. Neural stem cells, neurons, and glia express receptors that mediate interactions with specific extracellular matrix molecules. Functional studies in vitro and genetic studies in mice have provided evidence that the extracellular matrix affects virtually all aspects of nervous system development and function. Here we will summarize recent findings that have shed light on the specific functions of defined extracellular matrix molecules on such diverse processes as neural stem cell differentiation, neuronal migration, the formation of axonal tracts, and the maturation and function of synapses in the peripheral and central nervous system. PMID:21123393

  9. [Functional anatomy of the central nervous system].

    PubMed

    Krainik, A; Feydy, A; Colombani, J M; Hélias, A; Menu, Y

    2003-03-01

    The central nervous system (CNS) has a particular regional functional anatomy. The morphological support of cognitive functions can now be depicted using functional imaging. Lesions of the central nervous system may be responsible of specific symptoms based on their location. Current neuroimaging techniques are able to show and locate precisely macroscopic lesions. Therefore, the knowledge of functional anatomy of the central nervous system is useful to link clinical disorders to symptomatic lesions. Using radio-clinical cases, we present the functional neuro-anatomy related to common cognitive impairments.

  10. Parasitic diseases of the central nervous system.

    PubMed

    Abdel Razek, Ahmed Abdel Khalek; Watcharakorn, Arvemas; Castillo, Mauricio

    2011-11-01

    This article reviews the characteristic imaging appearances of parasitic diseases of the central nervous system, including cysticercosis, toxoplasmosis, cystic echinococcosis, schistosomiasis, amebiasis, malariasis, sparganosis, paragonimiasis, and American and African trypanosomiases. Routine precontrast and postcontrast MR imaging helps in localization, characterization, delineation of extension, and follow-up of the parasitic lesions. Moreover, recently developed tools, such as diffusion, perfusion, and MR spectroscopy, help to differentiate parasitic diseases of the central nervous system from simulating lesions. Combining imaging findings with geographic prevalence, clinical history, and serologic tests is required for diagnosis of parasitic diseases of the central nervous system.

  11. Plasmalogen phospholipids protect internodal myelin from oxidative damage.

    PubMed

    Luoma, Adrienne M; Kuo, Fonghsu; Cakici, Ozgur; Crowther, Michelle N; Denninger, Andrew R; Avila, Robin L; Brites, Pedro; Kirschner, Daniel A

    2015-07-01

    Reactive oxygen species (ROS) are implicated in a range of degenerative conditions, including aging, neurodegenerative diseases, and neurological disorders. Myelin is a lipid-rich multilamellar sheath that facilitates rapid nerve conduction in vertebrates. Given the high energetic demands and low antioxidant capacity of the cells that elaborate the sheaths, myelin is considered intrinsically vulnerable to oxidative damage, raising the question whether additional mechanisms prevent structural damage. We characterized the structural and biochemical basis of ROS-mediated myelin damage in murine tissues from both central nervous system (CNS) and peripheral nervous system (PNS). To determine whether ROS can cause structural damage to the internodal myelin, whole sciatic and optic nerves were incubated ex vivo with a hydroxyl radical-generating system consisting of copper (Cu), hydrogen peroxide (HP), and ortho-phenanthroline (OP). Quantitative assessment of unfixed tissue by X-ray diffraction revealed irreversible compaction of myelin membrane stacking in both sciatic and optic nerves. Incubation in the presence of the hydroxyl radical scavenger sodium formate prevented this damage, implicating hydroxyl radical species. Myelin membranes are particularly enriched in plasmalogens, a class of ether-linked phospholipids proposed to have antioxidant properties. Myelin in sciatic nerve from plasmalogen-deficient (Pex7 knockout) mice was significantly more vulnerable to Cu/OP/HP-mediated ROS-induced compaction than myelin from WT mice. Our results directly support the role of plasmalogens as endogenous antioxidants providing a defense that protects ROS-vulnerable myelin.

  12. A role of peripheral myelin protein 2 in lipid homeostasis of myelinating Schwann cells.

    PubMed

    Zenker, Jennifer; Stettner, Mark; Ruskamo, Salla; Domènech-Estévez, Enric; Baloui, Hasna; Médard, Jean-Jacques; Verheijen, Mark H G; Brouwers, Jos F; Kursula, Petri; Kieseier, Bernd C; Chrast, Roman

    2014-09-01

    Peripheral myelin protein 2 (Pmp2, P2 or Fabp8), a member of the fatty acid binding protein family, was originally described together with myelin basic protein (Mbp or P1) and myelin protein zero (Mpz or P0) as one of the most abundant myelin proteins in the peripheral nervous system (PNS). Although Pmp2 is predominantly expressed in myelinated Schwann cells, its role in glia is currently unknown. To study its function in PNS biology, we have generated a complete Pmp2 knockout mouse (Pmp2(-/-) ). Comprehensive characterization of Pmp2(-/-) mice revealed a temporary reduction in their motor nerve conduction velocity (MNCV). While this change was not accompanied by any defects in general myelin structure, we detected transitory alterations in the myelin lipid profile of Pmp2(-/-) mice. It was previously proposed that Pmp2 and Mbp have comparable functions in the PNS suggesting that the presence of Mbp can partially mask the Pmp2(-/-) phenotype. Indeed, we found that Mbp lacking Shi(-/-) mice, similar to Pmp2(-/-) animals, have preserved myelin structure and reduced MNCV, but this phenotype was not aggravated in Pmp2(-/-) /Shi(-/-) mutants indicating that Pmp2 and Mbp do not substitute each other's functions in the PNS. These data, together with our observation that Pmp2 binds and transports fatty acids to membranes, uncover a role for Pmp2 in lipid homeostasis of myelinating Schwann cells.

  13. Prolonged myelination in human neocortical evolution

    PubMed Central

    Miller, Daniel J.; Duka, Tetyana; Stimpson, Cheryl D.; Schapiro, Steven J.; Baze, Wallace B.; McArthur, Mark J.; Fobbs, Archibald J.; Sousa, André M. M.; Šestan, Nenad; Wildman, Derek E.; Lipovich, Leonard; Kuzawa, Christopher W.; Hof, Patrick R.; Sherwood, Chet C.

    2012-01-01

    Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders. PMID:23012402

  14. Myelin architecture: zippering membranes tightly together.

    PubMed

    Bakhti, Mostafa; Aggarwal, Shweta; Simons, Mikael

    2014-04-01

    Rapid nerve conduction requires the coating of axons by a tightly packed multilayered myelin membrane. In the central nervous system, myelin is formed from cellular processes that extend from oligodendrocytes and wrap in a spiral fashion around an axon, resulting in the close apposition of adjacent myelin membrane bilayers. In this review, we discuss the physical principles underlying the zippering of the plasma membrane of oligodendrocytes at the cytoplasmic and extracellular leaflet. We propose that the interaction of the myelin basic protein with the cytoplasmic leaflet of the myelin bilayer triggers its polymerization into a fibrous network that drives membrane zippering and protein extrusion. In contrast, the adhesion of the extracellular surfaces of myelin requires the down-regulation of repulsive components of the glycocalyx, in order to uncover weak and unspecific attractive forces that bring the extracellular surfaces into close contact. Unveiling the mechanisms of myelin membrane assembly at the cytoplasmic and extracelluar sites may help to understand how the myelin bilayers are disrupted and destabilized in the different demyelinating diseases.

  15. [Parasitic diseases of the central nervous system].

    PubMed

    Schmutzhard, E

    2010-02-01

    Central nervous system infections and infestations by protozoa and helminths constitute a problem of increasing importance throughout all of central European and northern/western countries. This is partially due to the globalisation of our society, tourists and business people being more frequently exposed to parasitic infection/infestation in tropical countries than in moderate climate countries. On top of that, migrants may import chronic infestations and infections with parasitic pathogens, eventually also--sometimes exclusively--involving the nervous system. Knowledge of epidemiology, initial clinical signs and symptoms, diagnostic procedures as well as specific chemotherapeutic therapies and adjunctive therapeutic strategies is of utmost important in all of these infections and infestations of the nervous systems, be it by protozoa or helminths. This review lists, mainly in the form of tables, all possible infections and infestations of the nervous systems by protozoa and by helminths. Besides differentiating parasitic diseases of the nervous system seen in migrants, tourists etc., it is very important to have in mind that disease-related (e.g. HIV) or iatrogenic immunosuppression has led to the increased occurrence of a wide variety of parasitic infections and infestations of the nervous system (e. g. babesiosis, Chagas disease, Strongyloides stercoralis infestation, toxoplasmosis, etc.). PMID:20111855

  16. Autonomic nervous system functions in obese children.

    PubMed

    Yakinci, C; Mungen, B; Karabiber, H; Tayfun, M; Evereklioglu, C

    2000-05-01

    Childhood obesity is a complex syndrome, probably due to the multiplicity of contributing factors, contradictory literature information about etiology, prognosis, prevention and treatment. In the recent reports, autonomic nervous system (ANS) dysfunction has been documented in adult obesity. Autonomic nervous system functions in obese children are not clear. This study was planned to investigate autonomic nervous system function in childhood (7-13 years of age) obesity. Study and control groups consisted of 33 simple obese (23 boys and ten girls, mean age 9.5+/-1.4 years) and 30 healthy children (18 boys and 12 girls, mean age 10.1+/-1.8 years), respectively. Four non-invasive autonomic nervous system function tests (Orthostatic test, Valsalva ratio, 30/15 ratio, Heart rate responses to deep breathing) and general ophthalmic examination were performed on both groups. The difference between the obese and control groups was found statistically significant in Valsalva ratio, 30/15 ratio and Heart rate responses to deep breathing (P<0.025), and insignificant in Orthostatic test (P>0.05). Ophthalmic examinations were normal. The result of these tests suggested normal activity of sympathetic, and hypoactivity of parasympathetic nervous system, implying parasympathetic nervous system dysfunction as a risk factor or associated finding in childhood obesity. PMID:10814895

  17. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body. PMID:25026144

  18. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body.

  19. [Parasitic diseases of the central nervous system].

    PubMed

    Schmutzhard, E

    2010-02-01

    Central nervous system infections and infestations by protozoa and helminths constitute a problem of increasing importance throughout all of central European and northern/western countries. This is partially due to the globalisation of our society, tourists and business people being more frequently exposed to parasitic infection/infestation in tropical countries than in moderate climate countries. On top of that, migrants may import chronic infestations and infections with parasitic pathogens, eventually also--sometimes exclusively--involving the nervous system. Knowledge of epidemiology, initial clinical signs and symptoms, diagnostic procedures as well as specific chemotherapeutic therapies and adjunctive therapeutic strategies is of utmost important in all of these infections and infestations of the nervous systems, be it by protozoa or helminths. This review lists, mainly in the form of tables, all possible infections and infestations of the nervous systems by protozoa and by helminths. Besides differentiating parasitic diseases of the nervous system seen in migrants, tourists etc., it is very important to have in mind that disease-related (e.g. HIV) or iatrogenic immunosuppression has led to the increased occurrence of a wide variety of parasitic infections and infestations of the nervous system (e. g. babesiosis, Chagas disease, Strongyloides stercoralis infestation, toxoplasmosis, etc.).

  20. Social Experience-Dependent Myelination: An Implication for Psychiatric Disorders.

    PubMed

    Toritsuka, Michihiro; Makinodan, Manabu; Kishimoto, Toshifumi

    2015-01-01

    Myelination is one of the strategies to promote the conduction velocity of axons in order to adjust to evolving environment in vertebrates. It has been shown that myelin formation depends on genetic programing and experience, including multiple factors, intracellular and extracellular molecules, and neuronal activities. Recently, accumulating studies have shown that myelination in the central nervous system changes more dynamically in response to neuronal activities and experience than expected. Among experiences, social experience-dependent myelination draws attention as one of the critical pathobiologies of psychiatric disorders. In this review, we summarize the mechanisms of neuronal activity-dependent and social experience-dependent myelination and discuss the contribution of social experience-dependent myelination to the pathology of psychiatric disorders. PMID:26078885

  1. Social Experience-Dependent Myelination: An Implication for Psychiatric Disorders

    PubMed Central

    Toritsuka, Michihiro; Kishimoto, Toshifumi

    2015-01-01

    Myelination is one of the strategies to promote the conduction velocity of axons in order to adjust to evolving environment in vertebrates. It has been shown that myelin formation depends on genetic programing and experience, including multiple factors, intracellular and extracellular molecules, and neuronal activities. Recently, accumulating studies have shown that myelination in the central nervous system changes more dynamically in response to neuronal activities and experience than expected. Among experiences, social experience-dependent myelination draws attention as one of the critical pathobiologies of psychiatric disorders. In this review, we summarize the mechanisms of neuronal activity-dependent and social experience-dependent myelination and discuss the contribution of social experience-dependent myelination to the pathology of psychiatric disorders. PMID:26078885

  2. Social Experience-Dependent Myelination: An Implication for Psychiatric Disorders.

    PubMed

    Toritsuka, Michihiro; Makinodan, Manabu; Kishimoto, Toshifumi

    2015-01-01

    Myelination is one of the strategies to promote the conduction velocity of axons in order to adjust to evolving environment in vertebrates. It has been shown that myelin formation depends on genetic programing and experience, including multiple factors, intracellular and extracellular molecules, and neuronal activities. Recently, accumulating studies have shown that myelination in the central nervous system changes more dynamically in response to neuronal activities and experience than expected. Among experiences, social experience-dependent myelination draws attention as one of the critical pathobiologies of psychiatric disorders. In this review, we summarize the mechanisms of neuronal activity-dependent and social experience-dependent myelination and discuss the contribution of social experience-dependent myelination to the pathology of psychiatric disorders.

  3. Arf6 mediates Schwann cell differentiation and myelination.

    PubMed

    Torii, Tomohiro; Miyamoto, Yuki; Yamamoto, Masahiro; Ohbuchi, Katsuya; Tsumura, Hideki; Kawahara, Kazuko; Tanoue, Akito; Sakagami, Hiroyuki; Yamauchi, Junji

    2015-09-25

    During development of the peripheral nervous system (PNS), Schwann cells wrap neuronal axons, becoming the myelin sheaths that help axonal functions. While the intercellular signals controlling the myelination process between Schwann cells and peripheral neurons are well studied, the transduction of these signals in Schwann cells still remains elusive. Here, we show that Arf6, an Arf protein of the small GTPase family, is involved in promoting the myelination process. Knockdown of Arf6 with the small-interfering (si)RNA in primary Schwann cells markedly decreases dibutyl-cyclic AMP-induced myelin marker protein expression, indicating that Arf6 plays a role in differentiation-like phenotypic changes. To obtain in vivo evidence, we generated small-hairpin (sh)RNA transgenic mice targeting Arf6 for Schwann cells. Transgenic mice exhibited reduced myelin thickness compared to littermate controls, consistent with the defective myelin formation observed in the transgenic mouse-derived Schwann cell and neuronal culture system. Transgenic mice also exhibited decreased phosphorylation of myelination-related signaling molecules such as Akt kinase cascade proteins as well as downregulation of myelin marker proteins. These results suggest that signaling through Arf6 is required for Schwann cell myelination, adding Arf6 to the list of intracellular signaling molecules involved in the myelination process.

  4. Autoantibodies to nervous system-specific proteins are elevated in sera of flight crew members: biomarkers for nervous system injury.

    PubMed

    Abou-Donia, Mohamed B; Abou-Donia, Martha M; ElMasry, Eman M; Monro, Jean A; Mulder, Michel F A

    2013-01-01

    This descriptive study reports the results of assays performed to detect circulating autoantibodies in a panel of 7 proteins associated with the nervous system (NS) in sera of 12 healthy controls and a group of 34 flight crew members including both pilots and attendants who experienced adverse effects after exposure to air emissions sourced to the ventilation system in their aircrafts and subsequently sought medical attention. The proteins selected represent various types of proteins present in nerve cells that are affected by neuronal degeneration. In the sera samples from flight crew members and healthy controls, immunoglobin (IgG) was measured using Western blotting against neurofilament triplet proteins (NFP), tubulin, microtubule-associated tau proteins (tau), microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and glial S100B protein. Significant elevation in levels of circulating IgG-class autoantibodies in flight crew members was found. A symptom-free pilot was sampled before symptoms and then again afterward. This pilot developed clinical problems after flying for 45 h in 10 d. Significant increases in autoantibodies were noted to most of the tested proteins in the serum of this pilot after exposure to air emissions. The levels of autoantibodies rose with worsening of his condition compared to the serum sample collected prior to exposure. After cessation of flying for a year, this pilot's clinical condition improved, and eventually he recovered and his serum autoantibodies against nervous system proteins decreased. The case study with this pilot demonstrates a temporal relationship between exposure to air emissions, clinical condition, and level of serum autoantibodies to nervous system-specific proteins. Overall, these results suggest the possible development of neuronal injury and gliosis in flight crew members anecdotally exposed to cabin air emissions containing organophosphates. Thus, increased

  5. [Inflammatory and autoimmune reactions in different forms of nervous system functioning disorders].

    PubMed

    Otman, I N; Zozulya, S A; Sarmanova, Z V; Klushnik, T P

    2015-01-01

    Parameters of innate (the leukocyte elastase (LE) and alpha1-proteinase inhibitor (α-1-PI) activity) and adaptive immunity (the level of autoantibodies to neuroantigens nerve growth factor (NGF) and myelin basic protein (MPB)) were studied over time in the blood serum of 107 children with perinatal hypoxic-ischemic encephalopathy; 188 children with autism spectrum disorder; 108 patients with schizophrenia. The correlations between immunological parameters and clinical status assessment in all groups of patients using psychometric scales were analyzed. The involvement of innate immunity, i.e. inflammatory reactions, in pathogenesis of all analyzed forms of nervous system functioning disorders was confirmed. The activation of adaptive immunity, i.e. autoimmune reactions, was found only in the group of patients with the most severe forms of nervous system functioning endogenous disorders. The results indicate that the inflammatory and autoimmune reactions are pathogenic mechanism of all studied forms of nervous system functioning disorders. PMID:26852601

  6. Local Nitric Oxide Production in Viral and Autoimmune Diseases of the Central Nervous System

    NASA Astrophysics Data System (ADS)

    Hooper, D. Craig; Tsuyoshi Ohnishi, S.; Kean, Rhonda; Numagami, Yoshihiro; Dietzschold, Bernhard; Koprowski, Hilary

    1995-06-01

    Because of the short half-life of NO, previous studies implicating NO in central nervous system pathology during infection had to rely on the demonstration of elevated levels of NO synthase mRNA or enzyme expression or NO metabolites such as nitrate and nitrite in the infected brain. To more definitively investigate the potential causative role of NO in lesions of the central nervous system in animals infected with neurotropic viruses or suffering from experimental allergic encephalitis, we have determined directly the levels of NO present in the central nervous system of such animals. Using spin trapping of NO and electron paramagnetic resonance spectroscopy, we confirm here that copious amounts of NO (up to 30-fold more than control) are elaborated in the brains of rats infected with rabies virus or borna disease virus, as well as in the spinal cords of rats that had received myelin basic protein-specific T cells.

  7. Central nervous system complications after liver transplantation.

    PubMed

    Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu

    2015-08-01

    We investigated the diversity of central nervous system complications after liver transplantation in terms of clinical manifestations and temporal course. Liver transplantation is a lifesaving option for end stage liver disease patients but post-transplantation neurologic complications can hamper recovery. Between 1 January 2001 and 31 December 2010, patients who had undergone liver transplantation at a single tertiary university hospital were included. We reviewed their medical records and brain imaging data and classified central nervous system complications into four categories including vascular, metabolic, infectious and neoplastic. The onset of central nervous system complications was grouped into five post-transplantation intervals including acute (within 1 month), early subacute (1-3 months), late subacute (3-12 months), chronic (1-3 years), and long-term (after 3 years). During follow-up, 65 of 791 patients (8.2%) experienced central nervous system complications, with 30 occurring within 1 month after transplantation. Vascular etiology was the most common (27 patients; 41.5%), followed by metabolic (23; 35.4%), infectious (nine patients; 13.8%), and neoplastic (six patients). Metabolic encephalopathy with altered consciousness was the most common etiology during the acute period, followed by vascular disorders. An initial focal neurologic deficit was detected in vascular and neoplastic complications, whereas metabolic and infectious etiologies presented with non-focal symptoms. Our study shows that the etiology of central nervous system complications after liver transplantation changes over time, and initial symptoms can help to predict etiology.

  8. Identifying the Cellular Targets of Drug Action in the Central Nervous System Following Corticosteroid Therapy

    PubMed Central

    2013-01-01

    Corticosteroid (CS) therapy is used widely in the treatment of a range of pathologies, but can delay production of myelin, the insulating sheath around central nervous system nerve fibers. The cellular targets of CS action are not fully understood, that is, “direct” action on cells involved in myelin genesis [oligodendrocytes and their progenitors the oligodendrocyte precursor cells (OPCs)] versus “indirect” action on other neural cells. We evaluated the effects of the widely used CS dexamethasone (DEX) on purified OPCs and oligodendrocytes, employing complementary histological and transcriptional analyses. Histological assessments showed no DEX effects on OPC proliferation or oligodendrocyte genesis/maturation (key processes underpinning myelin genesis). Immunostaining and RT-PCR analyses show that both cell types express glucocorticoid receptor (GR; the target for DEX action), ruling out receptor expression as a causal factor in the lack of DEX-responsiveness. GRs function as ligand-activated transcription factors, so we simultaneously analyzed DEX-induced transcriptional responses using microarray analyses; these substantiated the histological findings, with limited gene expression changes in DEX-treated OPCs and oligodendrocytes. With identical treatment, microglial cells showed profound and global changes post-DEX addition; an unexpected finding was the identification of the transcription factor Olig1, a master regulator of myelination, as a DEX responsive gene in microglia. Our data indicate that CS-induced myelination delays are unlikely to be due to direct drug action on OPCs or oligodendrocytes, and may occur secondary to alterations in other neural cells, such as the immune component. To the best of our knowledge, this is the first comparative molecular and cellular analysis of CS effects in glial cells, to investigate the targets of this major class of anti-inflammatory drugs as a basis for myelination deficits. PMID:24147833

  9. Myelin inhibits oligodendroglial maturation and regulates oligodendrocytic transcription factor expression.

    PubMed

    Plemel, Jason R; Manesh, Sohrab B; Sparling, Joseph S; Tetzlaff, Wolfram

    2013-09-01

    Myelin loss is a hallmark of multiple sclerosis (MS) and promoting central nervous system myelin repair has become a major therapeutic target. Despite the presence of oligodendrocytes precursors cells (OPCs) in chronic lesions of MS, remyelination often fails. The mechanism underlying this failure of remyelination remains unknown, but it is hypothesized that environmental cues act to inhibit the maturation/differentiation of oligodendroglia, preventing remyelination. The rate of CNS remyelination is correlated to the speed of phagocytosis of myelin debris, which is present following demyelination and trauma. Thus, myelin debris could inhibit CNS remyelination. Here, we demonstrate that OPCs cultured on myelin were robustly inhibited in their maturation, as characterized by the decreased expression of immature and mature oligodendrocytes markers, the impaired production of myelin gene products, as well as their stalled morphological complexity relative to OPCs cultured on a control substrate. OPCs in contact with myelin stopped proliferating and decreased the expression of OPC markers to a comparable degree as cells grown on a control substrate. The expression of two transcription factors known to prevent OPC differentiation and maturation were increased in cells that were in contact with myelin: inhibitor of differentiation family (ID) members 2 and 4. Overexpression of ID2 and ID4 in OPCs was previously reported to decrease the percentage of cells expressing mature oligodendrocyte markers. However, knockdown of ID2 and/or ID4 in OPCs did not increase oligodendroglial maturation on or off of myelin, suggesting that contact with myelin regulates additional regulatory elements.

  10. Hydrogels for central nervous system therapeutic strategies.

    PubMed

    Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi

    2015-12-01

    The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described.

  11. Comparative anatomy of the autonomic nervous system.

    PubMed

    Nilsson, Stefan

    2011-11-16

    This short review aims to point out the general anatomical features of the autonomic nervous systems of non-mammalian vertebrates. In addition it attempts to outline the similarities and also the increased complexity of the autonomic nervous patterns from fish to tetrapods. With the possible exception of the cyclostomes, perhaps the most striking feature of the vertebrate autonomic nervous system is the similarity between the vertebrate classes. An evolution of the complexity of the system can be seen, with the segmental ganglia of elasmobranchs incompletely connected longitudinally, while well developed paired sympathetic chains are present in teleosts and the tetrapods. In some groups the sympathetic chains may be reduced (dipnoans and caecilians), and have yet to be properly described in snakes. Cranial autonomic pathways are present in the oculomotor (III) and vagus (X) nerves of gnathostome fish and the tetrapods, and with the evolution of salivary and lachrymal glands in the tetrapods, also in the facial (VII) and glossopharyngeal (IX) nerves.

  12. Vulnerable processes of nervous system development: a review of markers and methods.

    PubMed

    Barone, S; Das, K P; Lassiter, T L; White, L D

    2000-01-01

    The susceptibility of the developing nervous system to damage following exposure to environmental contaminants has been well recognized. More recently, from a regulatory perspective, an increased emphasis has been placed on the vulnerability of the developing nervous system to damage following pesticide exposure. The publication of the National Academy of Sciences (NAS) report on Pesticides in the Diets of Infants and Children (1995) and the passage of the Food Quality Protection Act (FQPA) and Safe Drinking Water Act (SDWA) amendments have significantly escalated the scientific debate regarding age-related susceptibility. Key concerns raised in the NAS report include the qualitative and quantitative differences that distinguish the developing nervous system from that of the adult. It was suggested that neurotoxicity testing on adult animals alone may not be predictive of these differences in susceptibility. The age-related susceptibility of the nervous system is compounded by the protracted period of time over which this complex organ system develops. This temporal vulnerability spans the embryonic, fetal, infant, and adolescent periods. Normal development of the nervous system requires the concomitant and coordinated ontogeny of proliferation, migration, differentiation, synaptogenesis, gliogenesis, myelination and apoptosis to occur in a temporally- and regionally-dependent manner. Perturbations of these processes during development can result in long-term irreversible consequences that affect the structure and function of the nervous system and could account for qualitative differences in age-related susceptibility of the developing nervous system as compared to the adult nervous system. A discussion of developmental milestones and the relevance of transient effects on developmental endpoints are presented. Transient effects following developmental perturbations can be missed or dismissed depending on the experimental design or screening strategy employed. This

  13. Protective autoimmunity in the nervous system.

    PubMed

    Graber, Jerome J; Dhib-Jalbut, Suhayl

    2009-02-01

    The immune system can play both detrimental and beneficial roles in the nervous system. Multiple arms of the immune system, including T cells, B cells, NK cells, mast cells, macrophages, dendritic cells, microglia, antibodies, complement and cytokines participate in limiting damage to the nervous system during toxic, ischemic, hemorrhagic, infective, degenerative, metabolic and immune-mediated insults and also assist in the process of repair after injury has occurred. Immune cells have been shown to produce neurotrophic growth factors and interact with neurons and glial cells to preserve them from injury and stimulate growth and repair. The immune system also appears to participate in proliferation of neural progenitor stem cells and their migration to sites of injury. Neural stem cells can also modify the immune response in the central and peripheral nervous system to enhance neuroprotective effects. Evidence for protective and reparative functions of the immune system has been found in diverse neurologic diseases including traumatic injury, ischemic and hemorrhagic stroke, multiple sclerosis, infection, and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis). Existing therapies including glatiramer acetate, interferon-beta and immunoglobulin have been shown to augment the protective and regenerative aspects of the immune system in humans, and other experimental interventions such as vaccination, minocycline, antibodies and neural stem cells, have shown promise in animal models of disease. The beneficent aspects of the immune response in the nervous system are beginning to be appreciated and their potential as pharmacologic targets in neurologic disease is being explored. PMID:19000712

  14. The Injured Nervous System: A Darwinian Perspective

    PubMed Central

    Weil, Zachary M.; Norman, Greg J.; DeVries, A. Courtney; Nelson, Randy J.

    2008-01-01

    Much of the permanent damage that occurs in response to nervous system damage (trauma, infection, ischemia, etc.) is mediated by endogenous secondary processes that can contribute to cell death and tissue damage (excitotoxicity, oxidative damage and inflammation). For humans to evolve mechanisms to minimize secondary pathophysiological events following CNS injuries, selection must occur for individuals who survive such insults. Two major factors limit the selection for beneficial responses to CNS insults: for many CNS disease states the principal risk factor is advanced, post-reproductive age and virtually all severe CNS traumas are fatal in the absence of modern medical intervention. An alternative hypothesis for the persistence of apparently maladaptive responses to CNS damage is that the secondary exacerbation of damage is the result of unavoidable evolutionary constraints. That is, the nervous system could not function under normal conditions if the mechanisms that caused secondary damage (e.g., excitotoxicity) in response to injury were decreased or eliminated. However, some vertebrate species normally inhabit environments (e.g. hypoxia in underground burrows) that could potentially damage their nervous systems. Yet, profound neuroprotective mechanisms have evolved in these animals indicating that natural selection can occur for traits that protect animals from nervous system damage. Many of the secondary processes and regeneration-inhibitory factors that exacerbate injuries likely persist because they have been adaptive over evolutionary time in the healthy nervous system. Therefore, it remains important that researchers consider the role of the processes in the healthy or developing nervous system to understand how they become dysregulated following injury. PMID:18602443

  15. Neutron scattering from myelin revisited: bilayer asymmetry and water-exchange kinetics

    SciTech Connect

    Denninger, Andrew R.; Demé, Bruno; Cristiglio, Viviana; LeDuc, Géraldine; Feller, W. Bruce; Kirschner, Daniel A.

    2014-12-01

    The structure of internodal myelin in the rodent central and peripheral nervous systems has been determined using neutron diffraction. The kinetics of water exchange in these tissues is also described. Rapid nerve conduction in the central and peripheral nervous systems (CNS and PNS, respectively) of higher vertebrates is brought about by the ensheathment of axons with myelin, a lipid-rich, multilamellar assembly of membranes. The ability of myelin to electrically insulate depends on the regular stacking of these plasma membranes and on the presence of a number of specialized membrane-protein assemblies in the sheath, including the radial component, Schmidt–Lanterman incisures and the axo–glial junctions of the paranodal loops. The disruption of this fine-structure is the basis for many demyelinating neuropathies in the CNS and PNS. Understanding the processes that govern myelin biogenesis, maintenance and destabilization requires knowledge of myelin structure; however, the tight packing of internodal myelin and the complexity of its junctional specializations make myelin a challenging target for comprehensive structural analysis. This paper describes an examination of myelin from the CNS and PNS using neutron diffraction. This investigation revealed the dimensions of the bilayers and aqueous spaces of myelin, asymmetry between the cytoplasmic and extracellular leaflets of the membrane, and the distribution of water and exchangeable hydrogen in internodal multilamellar myelin. It also uncovered differences between CNS and PNS myelin in their water-exchange kinetics.

  16. Repair in the central nervous system.

    PubMed

    Fitzgerald, J; Fawcett, J

    2007-11-01

    The subject of central nervous system damage includes a wide variety of problems, from the slow selective 'picking off' of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system. PMID:17998174

  17. Vitamin D and the central nervous system.

    PubMed

    Wrzosek, Małgorzata; Łukaszkiewicz, Jacek; Wrzosek, Michał; Jakubczyk, Andrzej; Matsumoto, Halina; Piątkiewicz, Paweł; Radziwoń-Zaleska, Maria; Wojnar, Marcin; Nowicka, Grażyna

    2013-01-01

    Vitamin D is formed in human epithelial cells via photochemical synthesis and is also acquired from dietary sources. The so-called classical effect of this vitamin involves the regulation of calcium homeostasis and bone metabolism. Apart from this, non-classical effects of vitamin D have recently gained renewed attention. One important yet little known of the numerous functions of vitamin D is the regulation of nervous system development and function. The neuroprotective effect of vitamin D is associated with its influence on neurotrophin production and release, neuromediator synthesis, intracellular calcium homeostasis, and prevention of oxidative damage to nervous tissue. Clinical studies suggest that vitamin D deficiency may lead to an increased risk of disease of the central nervous system (CNS), particularly schizophrenia and multiple sclerosis. Adequate intake of vitamin D during pregnancy and the neonatal period seems to be crucial in terms of prevention of these diseases.

  18. Evolving specialization of the arthropod nervous system

    PubMed Central

    Jarvis, Erin; Bruce, Heather S.; Patel, Nipam H.

    2012-01-01

    The diverse array of body plans possessed by arthropods is created by generating variations upon a design of repeated segments formed during development, using a relatively small “toolbox” of conserved patterning genes. These attributes make the arthropod body plan a valuable model for elucidating how changes in development create diversity of form. As increasingly specialized segments and appendages evolved in arthropods, the nervous systems of these animals also evolved to control the function of these structures. Although there is a remarkable degree of conservation in neural development both between individual segments in any given species and between the nervous systems of different arthropod groups, the differences that do exist are informative for inferring general principles about the holistic evolution of body plans. This review describes developmental processes controlling neural segmentation and regionalization, highlighting segmentation mechanisms that create both ectodermal and neural segments, as well as recent studies of the role of Hox genes in generating regional specification within the central nervous system. We argue that this system generates a modular design that allows the nervous system to evolve in concert with the body segments and their associated appendages. This information will be useful in future studies of macroevolutionary changes in arthropod body plans, especially in understanding how these transformations can be made in a way that retains the function of appendages during evolutionary transitions in morphology. PMID:22723369

  19. The effect of space radiation of the nervous system

    NASA Astrophysics Data System (ADS)

    Gauger, Grant E.; Tobias, Cornelius A.; Yang, Tracy; Whitney, Monroe

    The long-term effects of irradiation by accelerated heavy ions on the structure and function of the nervous system have not been studied extensively. Although the adult brain is relatively resistant to low LET radiation, cellular studies indicate that individual heavy ions can produce serious membrane lesions and multiple chromatin breaks. Capillary hemorrhages may follow high LET particle irradiation of the developing brain as high RBE effects. Evidence has been accumulating that the glial system and blood-brain barrier (BBB) are relatively sensitive to injury by ionizing radiation. While DNA repair is active in neural systems, it may be assumed that a significant portion of this molecular process is misrepair. Since the expression of cell lethality usually requires cell division, and nerve cells have an extremely low rate of division, it is possible that some of the characteristic changes of premature aging may represent a delayed effect of chromatin misrepair in brain. Altered microcirculation, decreased local metabolism, entanglement and reduction in synaptic density, premature loss of neurons, myelin degeneration, and glial proliferation are late signs of such injuries. HZE particles are very efficient in producing carcinogenic cell transformation, reaching a peak for iron particles. The promotion of viral transformation is also efficient up to an energy transfer of approximately 300 keV/micron. The RBE for carcinogenesis in nerve tissues remains unknown. On the basis of available information concerning HZE particle flux in interplanetary space, only general estimates of the magnitude of the effects of long-term spaceflight on some nervous system parameters may be constructed.

  20. Zebrafish as a Model to Investigate CNS Myelination

    PubMed Central

    Preston, Marnie A.; Macklin, Wendy B.

    2015-01-01

    Myelin plays a critical role in proper neuronal function by providing trophic and metabolic support to axons and facilitating energy-efficient saltatory conduction. Myelination is influenced by numerous molecules including growth factors, hormones, transmembrane receptors and extracellular molecules, which activate signaling cascades that drive cellular maturation. Key signaling molecules and downstream signaling cascades controlling myelination have been identified in cell culture systems. However, in vitro systems are not able to faithfully replicate the complex in vivo signaling environment that occurs during development or following injury. Currently, it remains time-consuming and expensive to investigate myelination in vivo in rodents, the most widely used model for studying mammalian myelination. As such, there is a need for alternative in vivo myelination models, particularly ones that can test molecular mechanisms without removing oligodendrocyte lineage cells from their native signaling environment or disrupting intercellular interactions with other cell types present during myelination. Here, we review the ever-increasing role of zebrafish in studies uncovering novel mechanisms controlling vertebrate myelination. These innovative studies range from observations of the behavior of single cells during in vivo myelination as well as mutagenesis- and pharmacology-based screens in whole animals. Additionally, we discuss recent efforts to develop novel models of demyelination and oligodendrocyte cell death in adult zebrafish for the study of cellular behavior in real time during repair and regeneration of damaged nervous systems. PMID:25263121

  1. Zebrafish as a model to investigate CNS myelination.

    PubMed

    Preston, Marnie A; Macklin, Wendy B

    2015-02-01

    Myelin plays a critical role in proper neuronal function by providing trophic and metabolic support to axons and facilitating energy-efficient saltatory conduction. Myelination is influenced by numerous molecules including growth factors, hormones, transmembrane receptors and extracellular molecules, which activate signaling cascades that drive cellular maturation. Key signaling molecules and downstream signaling cascades controlling myelination have been identified in cell culture systems. However, in vitro systems are not able to faithfully replicate the complex in vivo signaling environment that occurs during development or following injury. Currently, it remains time-consuming and expensive to investigate myelination in vivo in rodents, the most widely used model for studying mammalian myelination. As such, there is a need for alternative in vivo myelination models, particularly ones that can test molecular mechanisms without removing oligodendrocyte lineage cells from their native signaling environment or disrupting intercellular interactions with other cell types present during myelination. Here, we review the ever-increasing role of zebrafish in studies uncovering novel mechanisms controlling vertebrate myelination. These innovative studies range from observations of the behavior of single cells during in vivo myelination as well as mutagenesis- and pharmacology-based screens in whole animals. Additionally, we discuss recent efforts to develop novel models of demyelination and oligodendrocyte cell death in adult zebrafish for the study of cellular behavior in real time during repair and regeneration of damaged nervous systems.

  2. Evolution of basal deuterostome nervous systems.

    PubMed

    Holland, Linda Z

    2015-02-15

    Understanding the evolution of deuterostome nervous systems has been complicated by the by the ambiguous phylogenetic position of the Xenocoelomorpha (Xenoturbellids, acoel flat worms, nemertodermatids), which has been placed either as basal bilaterians, basal deuterostomes or as a sister group to the hemichordate/echinoderm clade (Ambulacraria), which is a sister group of the Chordata. None of these groups has a single longitudinal nerve cord and a brain. A further complication is that echinoderm nerve cords are not likely to be evolutionarily related to the chordate central nervous system. For hemichordates, opinion is divided as to whether either one or none of the two nerve cords is homologous to the chordate nerve cord. In chordates, opposition by two secreted signaling proteins, bone morphogenetic protein (BMP) and Nodal, regulates partitioning of the ectoderm into central and peripheral nervous systems. Similarly, in echinoderm larvae, opposition between BMP and Nodal positions the ciliary band and regulates its extent. The apparent loss of this opposition in hemichordates is, therefore, compatible with the scenario, suggested by Dawydoff over 65 years ago, that a true centralized nervous system was lost in hemichordates.

  3. Amino acid sequence of the encephalitogenic basic protein from human myelin

    PubMed Central

    Carnegie, P. R.

    1971-01-01

    Myelin from the central nervous system contains an unusual basic protein, which can induce experimental autoimmune encephalomyelitis. The basic protein from human brain was digested with trypsin and other enzymes and the sequence of the 170 amino acids was determined. The localization of the encephalitogenic determinants was described. Possible roles for the protein in the structure and function of myelin are discussed. PMID:4108501

  4. Physiological functions of the small GTPase Arf6 in the nervous system

    PubMed Central

    Akiyama, Masahiro; Kanaho, Yasunori

    2015-01-01

    The small GTPase ADP-ribosylation factor 6 (Arf6) plays important roles in membrane dynamics-based neuronal cell events such as neurite outgrowth and spine formation. However, physiological functions of Arf6 in the nervous system at whole animal level have not yet been explored. We have recently generated conditional knockout mice lacking Arf6 in neurons or oligodendrocytes of central nervous system (CNS) or both cell lineages, and analyzed them. We found that ablation of Arf6 gene from neurons, but not from oligodendrocytes, caused the defect in axon myelination at the fimbria of hippocampus (Fim) and corpus callosum (CC). We also found that migration of oligodendrocyte precursor cells (OPCs) from the subventricular zone to the Fim and CC in mice lacking Arf6 in neurons was impaired. Finally, it was found that secretion of fibroblast growth factor-2 (FGF-2), a guidance factor for OPC migration, from hippocampi lacking Arf6 was impaired. Collectively, these findings demonstrate that Arf6 in neurons of the CNS plays an important role in OPC migration by regulating secretion of FGF-2 from neurons, thereby contributing to the axon myelination. Here, we discuss our current understanding of physiological functions of Arf6 in the nervous system. PMID:26291245

  5. Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

    PubMed Central

    Taveggia, Carla

    2014-01-01

    Abstract Significance: Iron is the most abundant transition metal in biology and an essential cofactor for many cellular enzymes. Iron homeostasis impairment is also a component of peripheral neuropathies. Recent Advances: During the past years, much effort has been paid to understand the molecular mechanism involved in maintaining systemic iron homeostasis in mammals. This has been stimulated by the evidence that iron dyshomeostasis is an initial cause of several disorders, including genetic and sporadic neurodegenerative disorders. Critical Issues: However, very little has been done to investigate the physiological role of iron in peripheral nervous system (PNS), despite the development of suitable cellular and animal models. Future Directions: To stimulate research on iron metabolism and peripheral neuropathy, we provide a summary of the knowledge on iron homeostasis in the PNS, on its transport across the blood–nerve barrier, its involvement in myelination, and we identify unresolved questions. Furthermore, we comment on the role of iron in iron-related disorder with peripheral component, in demyelinating and metabolic peripheral neuropathies. Antioxid. Redox Signal. 21, 634–648. PMID:24409826

  6. YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells.

    PubMed

    Poitelon, Yannick; Lopez-Anido, Camila; Catignas, Kathleen; Berti, Caterina; Palmisano, Marilena; Williamson, Courtney; Ameroso, Dominique; Abiko, Kansho; Hwang, Yoonchan; Gregorieff, Alex; Wrana, Jeffrey L; Asmani, Mohammadnabi; Zhao, Ruogang; Sim, Fraser James; Wrabetz, Lawrence; Svaren, John; Feltri, Maria Laura

    2016-07-01

    Myelination is essential for nervous system function. Schwann cells interact with neurons and the basal lamina to myelinate axons using known receptors, signals and transcription factors. In contrast, the transcriptional control of axonal sorting and the role of mechanotransduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. We describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice, we show that Taz is required in Schwann cells for radial sorting and myelination and that Yap is redundant with Taz. Yap and Taz are activated in Schwann cells by mechanical stimuli and regulate Schwann cell proliferation and transcription of basal lamina receptor genes, both necessary for radial sorting of axons and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells.

  7. Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex.

    PubMed

    Tomassy, Giulio Srubek; Berger, Daniel R; Chen, Hsu-Hsin; Kasthuri, Narayanan; Hayworth, Kenneth J; Vercelli, Alessandro; Seung, H Sebastian; Lichtman, Jeff W; Arlotta, Paola

    2014-04-18

    Myelin is a defining feature of the vertebrate nervous system. Variability in the thickness of the myelin envelope is a structural feature affecting the conduction of neuronal signals. Conversely, the distribution of myelinated tracts along the length of axons has been assumed to be uniform. Here, we traced high-throughput electron microscopy reconstructions of single axons of pyramidal neurons in the mouse neocortex and built high-resolution maps of myelination. We find that individual neurons have distinct longitudinal distribution of myelin. Neurons in the superficial layers displayed the most diversified profiles, including a new pattern where myelinated segments are interspersed with long, unmyelinated tracts. Our data indicate that the profile of longitudinal distribution of myelin is an integral feature of neuronal identity and may have evolved as a strategy to modulate long-distance communication in the neocortex.

  8. Enhanced Action Potential Passage Through the Node of Ranvier of Myelinated Axons via Proton Hopping.

    PubMed

    Kier, Lemont; Hall, Lowell; Tombes, Robert M

    2015-01-01

    Nerve impulses travel along myelinated axons as much as 300-fold faster than they do along unmyelinated axons. Myelination is essential for normal nervous system behavior in vertebrates as illustrated by leukodystrophies, such as amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS), where myelin is degenerated or damaged. The increased conduction velocity that occurs in myelinated axons is dependent on gaps in the myelin called Nodes of Ranvier that are enriched in ion channels. These Nodes are separated by long stretches of myelin insulation where no transmembrane ion conductance occurs. It is believed that the action potential jumps or skips between nodes, conserving its information content, while maintaining its speed. In this study, a model is presented that implicates Nodes of Ranvier as responsible for regenerating the proton hopping that is responsible for nerve impulse conductance in myelinated axons.

  9. Gravitational Study of the Central Nervous System

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.

    1983-01-01

    A series of experiments conducted at 1G are discussed with reference to the role of calcium ions in information processing by the central nervous system. A technique is described which allows thin sections of a mammalian hippocampus to be isolated while maintaining neural activity. Two experiments carried out in hypergravic fields are also addressed; one investigating altered stimulation in the auditory system, the other determining temperature regulation responses in hypergravic fields.

  10. Possible microwave mechanisms of the mammalian nervous system.

    PubMed

    Stocklin, P L; Stocklin, B F

    1979-01-01

    The hypothesis is examined that the living mammal generates and uses electromagnetic waves in the lower microwave frequency region as an integral part of the functioning of central and peripheral nervous systems. Analysis of the potential energy of a protein integral to the neural membrane compared to that of an extracellular positive ion yields major known features of action potential generation, and identification of the integral protein as a microwave emitter and absorber by changes in rotational energy state. Prolate spheroidal analysis of the adult human brain/skull cavity shows capability to support modes in the range 200 MHz to 3 GHz; spatial mode properties correspond to gross anatomy and neuromorphology of the brain. Phase-lock loop interaction between lower microwave modes and action potential conduction results in pulse microwave/action potential generation observable by EEG instrumentation as brain waves; alpha waves occur if the corpus callosum is the major neural tract involved. Spatially consistent Lorentz forces of standing microwaves provide physical basis for correspondence of spatial properties of microwave modes with brain anatomy, and for the formation of myelin sheath and the nodes of Ranvier on larger neurons.

  11. Myelin membrane assembly is driven by a phase transition of myelin basic proteins into a cohesive protein meshwork.

    PubMed

    Aggarwal, Shweta; Snaidero, Nicolas; Pähler, Gesa; Frey, Steffen; Sánchez, Paula; Zweckstetter, Markus; Janshoff, Andreas; Schneider, Anja; Weil, Marie-Theres; Schaap, Iwan A T; Görlich, Dirk; Simons, Mikael

    2013-01-01

    Rapid conduction of nerve impulses requires coating of axons by myelin. To function as an electrical insulator, myelin is generated as a tightly packed, lipid-rich multilayered membrane sheath. Knowledge about the mechanisms that govern myelin membrane biogenesis is required to understand myelin disassembly as it occurs in diseases such as multiple sclerosis. Here, we show that myelin basic protein drives myelin biogenesis using weak forces arising from its inherent capacity to phase separate. The association of myelin basic protein molecules to the inner leaflet of the membrane bilayer induces a phase transition into a cohesive mesh-like protein network. The formation of this protein network shares features with amyloid fibril formation. The process is driven by phenylalanine-mediated hydrophobic and amyloid-like interactions that provide the molecular basis for protein extrusion and myelin membrane zippering. These findings uncover a physicochemical mechanism of how a cytosolic protein regulates the morphology of a complex membrane architecture. These results provide a key mechanism in myelin membrane biogenesis with implications for disabling demyelinating diseases of the central nervous system.

  12. [Emotion, amygdala, and autonomic nervous system].

    PubMed

    Ueyama, Takashi

    2012-10-01

    Emotion refers to the dynamic changes of feeling accompanied by the alteration of physical and visceral activities. Autonomic nervous system (sympathetic and parasympathetic) regulates the visceral activities. Therefore, monitoring and analyzing autonomic nervous activity help understand the emotional changes. To this end, the survey of the expression of immediate early genes (IEGs), such as c-Fos in the brain and target organs, and the viral transneuronal labeling method using the pseudorabies virus (PRV) have enabled the visualization of the neurocircuitry of emotion. By comparing c-Fos expression and data from PRV or other neuroanatomical labeling techniques, the central sites that regulate emotional stress-induced autonomic activation can be deduced. Such regions have been identified in the limbic system (e. g., the extended amygdaloid complex; lateral septum; and infralimbic, insular, and ventromedial temporal cortical regions), as well as in several hypothalamic and brainstem nuclei. The amygdala is structurally diverse and comprises several subnuclei, which play a role in emotional process via projections from the cortex and a variety of subcortical structures. All amygdaloid subnuclei receive psychological information from other limbic systems, while the lateral and central subnuclei receive peripheral and sensory information. Output to the hypothalamus and peripheral sympathetic system mainly originates from the medial amygdala. As estrogen receptor α, estrogen receptor β, and androgen receptor are expressed in the medial amygdala, sex steroids may modulate the autonomic nervous activities.

  13. [Central nervous system tumors in pregnancy].

    PubMed

    Podciechowski, Lech; Nowakowska, Dorota; Bielak, Adam; Nowosławska, Emilia; Szymański, Wojciech; Polis, Lech; Krasomski, Grzechorz; Fiks, Tomasz; Wilczyński, Jan

    2003-12-01

    Central nervous system tumour in pregnancy constitutes a serious complication. Considering frequent difficulties in diagnostics and therapy, the aim of the study was to present our experience in management with pregnant women with brain and spinal cord tumours. Between 1988-2000, in The Research Institute Polish Mother's Memorial Hospital in Lodzi, 4 pregnant women had been diagnosed with brain and spinal cord tumours. The incidence of tumours complicating pregnancy was 1/11460. Two patients diagnosed at 29 weeks' gestation, underwent craniotomy and tumour resection during pregnancy. Two other women with central nervous system tumours diagnosed at 39 weeks' gestation, were operated in the postpartum period. The analysis of the postoperative period, gestation and/or postpartum period in all women and well-being of their new-borns confirm undertaken medical decisions. PMID:15029742

  14. Maintaining Genome Stability in the Nervous System

    PubMed Central

    McKinnon, Peter J.

    2014-01-01

    Active maintenance of genome stability is a prerequisite for the development and function of the nervous system. The high replication index during neurogenesis and the long life of mature neurons highlight the need for efficient cellular programs to safeguard genetic fidelity. Multiple DNA damage response pathways ensure that replication stress and other types of DNA lesions such as oxidative damage do not impact neural homeostasis. Numerous human neurologic syndromes result from defective DNA damage signaling and compromised genome integrity. These syndromes can involve different neuropathology, which highlights the diverse maintenance roles required for genome stability in the nervous system. Understanding how DNA damage signaling pathways promote neural development and preserve homeostasis is essential for understanding fundamental brain function. PMID:24165679

  15. Virus Infections in the Nervous System

    PubMed Central

    Koyuncu, Orkide O.; Hogue, Ian B.; Enquist, Lynn W.

    2013-01-01

    Virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (NS), spreading into the peripheral (PNS) and more rarely the central nervous systems (CNS). The CNS is protected from most virus infections by effective immune responses and multi-layer barriers. However, some viruses enter the NS with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. Most viruses in the NS are opportunistic or accidental pathogens, but a few, most notably the alpha herpesviruses and rabies virus, have evolved to enter the NS efficiently and exploit neuronal cell biology. Remarkably, the alpha herpesviruses can establish quiescent infections in the PNS, with rare but often fatal CNS pathology. Here we review how viruses gain access to and spread in the well-protected CNS, with particular emphasis on alpha herpesviruses, which establish and maintain persistent NS infections. PMID:23601101

  16. Imaging the fetal central nervous system.

    PubMed

    De Keersmaecker, B; Claus, F; De Catte, L

    2011-01-01

    The low prevalence of fetal central nervous system anomalies results in a restricted level of exposure and limited experience-- for most of the obstetricians involved in prenatal ultrasound. Sonographic guidelines for screening the fetal brain in a systematic way will probably increase the detection rate and enhance a correct referral to a tertiary care center, offering the patient a multidisciplinary approach of the condition. This paper aims to elaborate on prenatal sonographic and magnetic resonance imaging (MRI) diagnosis and outcome of various central nervous system malformations. Detailed neurosonographic investigation has become available through high resolution vaginal ultrasound probes and the development of a variety of 3D ultrasound modalities e.g. ultrasound tomographic imaging. In addition, fetal MRI is particularly helpful in the detection of gyration and neurulation-- anomalies and disorders of the gray and white matter. PMID:24753859

  17. Regeneration in the nervous system with erythropoietin

    PubMed Central

    Maiese, Kenneth

    2015-01-01

    Globally, greater than 30 million individuals are afflicted with disorders of the nervous system accompanied by tens of thousands of new cases annually with limited, if any, treatment options. Erythropoietin (EPO) offers an exciting and novel therapeutic strategy to address both acute and chronic neurodegenerative disorders. EPO governs a number of critical protective and regenerative mechanisms that can impact apoptotic and autophagic programmed cell death pathways through protein kinase B (Akt), sirtuins, mammalian forkhead transcription factors, and wingless signaling. Translation of the cytoprotective pathways of EPO into clinically effective treatments for some neurodegenerative disorders has been promising, but additional work is necessary. In particular, development of new treatments with erythropoiesis-stimulating agents such as EPO brings several important challenges that involve detrimental vascular outcomes and tumorigenesis. Future work that can effectively and safely harness the complexity of the signaling pathways of EPO will be vital for the fruitful treatment of disorders of the nervous system. PMID:26549969

  18. [Central nervous system malformations: neurosurgery correlates].

    PubMed

    Jiménez-León, Juan C; Betancourt-Fursow, Yaline M; Jiménez-Betancourt, Cristina S

    2013-09-01

    Congenital malformations of the central nervous system are related to alterations in neural tube formation, including most of the neurosurgical management entities, dysraphism and craniosynostosis; alterations of neuronal proliferation; megalencefaly and microcephaly; abnormal neuronal migration, lissencephaly, pachygyria, schizencephaly, agenesis of the corpus callosum, heterotopia and cortical dysplasia, spinal malformations and spinal dysraphism. We expose the classification of different central nervous system malformations that can be corrected by surgery in the shortest possible time and involving genesis mechanisms of these injuries getting better studied from neurogenic and neuroembryological fields, this involves connecting innovative knowledge areas where alteration mechanisms in dorsal induction (neural tube) and ventral induction (telencephalization) with the current way of correction, as well as the anomalies of cell proliferation and differentiation of neuronal migration and finally the complex malformations affecting the posterior fossa and current possibilities of correcting them.

  19. [Plasmapheresis in central nervous system disorders].

    PubMed

    Antozzi, Carlo

    2012-01-01

    Therapeutic plasmapheresis (TPE) has an established role in disorders of the peripheral nervous system, but its use in disorders of the central nervous system (CNS) does not rely upon evidence-based data. Nevertheless, TPE is currently used in severe acute forms of demyelinating disease (multiple sclerosis/acute encephalomyelitis) unresponsive to corticosteroids. Recently, antibodies against the water channel aquaporin-4 have been detected in patients affected by neuromyelitis optica (Devic syndrome) and their pathogenetic role has been demonstrated, supporting the use of TPE in this disease. TPE has been reported to be effective in some patients affected by stiff-person syndrome or limbic encephalitis associated with antibodies against voltagegated potassium channels. TPE has also been used in selected patients with treatment-resistant epilepsy or status epilepticus within complex syndromes of various etiologies. The available data still do not support the use of TPE in most paraneoplastic disorders of the CNS. PMID:22388844

  20. Remodeling myelination: implications for mechanisms of neural plasticity.

    PubMed

    Chang, Kae-Jiun; Redmond, Stephanie A; Chan, Jonah R

    2016-02-01

    One of the most significant paradigm shifts in membrane remodeling is the emerging view that membrane transformation is not exclusively controlled by cytoskeletal rearrangement, but also by biophysical constraints, adhesive forces, membrane curvature and compaction. One of the most exquisite examples of membrane remodeling is myelination. The advent of myelin was instrumental in advancing the nervous system during vertebrate evolution. With more rapid and efficient communication between neurons, faster and more complex computations could be performed in a given time and space. Our knowledge of how myelin-forming oligodendrocytes select and wrap axons has been limited by insufficient spatial and temporal resolution. By virtue of recent technological advances, progress has clarified longstanding controversies in the field. Here we review insights into myelination, from target selection to axon wrapping and membrane compaction, and discuss how understanding these processes has unexpectedly opened new avenues of insight into myelination-centered mechanisms of neural plasticity.

  1. Unconventional myosin ID is expressed in myelinating oligodendrocytes.

    PubMed

    Yamazaki, Reiji; Ishibashi, Tomoko; Baba, Hiroko; Yamaguchi, Yoshihide

    2014-10-01

    Myelin is a dynamic multilamellar structure that ensheathes axons and is crucial for normal neuronal function. In the central nervous system (CNS), myelin is produced by oligodendrocytes that wrap many layers of plasma membrane around axons. The dynamic membrane trafficking system, which relies on motor proteins, is required for myelin formation and maintenance. Previously, we found that myosin ID (Myo1d), a class I myosin, is enriched in the rat CNS myelin fraction. Myo1d is an unconventional myosin and has been shown to be involved in membrane trafficking in the recycling pathway in an epithelial cell line. Western blotting revealed that Myo1d expression begins early in myelinogenesis and continues to increase into adulthood. The localization of Myo1d in CNS myelin has not been reported, and the function of Myo1d in vivo remains unknown. To demonstrate the expression of Myo1d in CNS myelin and to begin to explore the function of Myo1d in myelination, we produced a new antibody against Myo1d that has a high titer and specificity for rat Myo1d. By using this antibody, we demonstrated that Myo1d is expressed in rat CNS myelin and is especially abundant in abaxonal and adaxonal regions (the outer and inner cytoplasm-containing loops, respectively), but that expression is low in peripheral nervous system myelin. In culture, Myo1d was expressed in mature rat oligodendrocytes. Furthermore, an increase in expression of Myo1d during maturation of CNS white matter (cerebellum and corpus callosum) was demonstrated by histological analysis. These results suggest that Myo1d may be involved in the formation and/or maintenance of CNS myelin.

  2. Peripheral Nervous System Manifestations of Infectious Diseases

    PubMed Central

    Brizzi, Kate T.

    2014-01-01

    Infectious causes of peripheral nervous system (PNS) disease are underrecognized but potentially treatable. Heightened awareness educed by advanced understanding of the presentations and management of these infections can aid diagnosis and facilitate treatment. In this review, we discuss the clinical manifestations, diagnosis, and treatment of common bacterial, viral, and parasitic infections that affect the PNS. We additionally detail PNS side effects of some frequently used antimicrobial agents. PMID:25360209

  3. Tuberculoma of the central nervous system.

    PubMed

    DeLance, Arthur R; Safaee, Michael; Oh, Michael C; Clark, Aaron J; Kaur, Gurvinder; Sun, Matthew Z; Bollen, Andrew W; Phillips, Joanna J; Parsa, Andrew T

    2013-10-01

    Tuberculosis is among the oldest and most devastating infectious diseases worldwide. Nearly one third of the world's population has active or latent disease, resulting in 1.5 million deaths annually. Central nervous system involvement, while rare, is the most severe form of tuberculosis. Manifestations include tuberculoma and tuberculous meningitis, with the majority of cases occurring in children and immunocompromised patients. Despite advancements in imaging and laboratory diagnostics, tuberculomas of the central nervous system remain a diagnostic challenge due to their insidious nature and nonspecific findings. On imaging studies tuberculous meningitis is characterized by diffuse basal enhancement, but tuberculomas may be indistinguishable from neoplasms. Early diagnosis is imperative, since clinical outcomes are largely dependent on timely treatment. Stereotactic biopsy with histopathological analysis can provide a definitive diagnosis, but is only recommended when non-invasive methods are inconclusive. Standard medical treatment includes rifampicin, isoniazid, pyrazinamide, and streptomycin or ethambutol. In cases of drug resistance, revision of the treatment regimen with second-line agents is recommended over the addition of a single drug to the first-line regimen. Advances in genomics have identified virulent strains of tuberculosis and are improving our understanding of host susceptibility. Neurosurgical referral is advised for patients with elevated intracranial pressure, seizures, or brain or spinal cord compression. This review synthesizes pertinent findings in the literature surrounding central nervous system tuberculoma in an effort to highlight recent advances in pathophysiology, diagnosis, and treatment.

  4. Stress, sex, and the enteric nervous system.

    PubMed

    Million, M; Larauche, M

    2016-09-01

    Made up of millions of enteric neurons and glial cells, the enteric nervous system (ENS) is in a key position to modulate the secretomotor function and visceral pain of the gastrointestinal tract. The early life developmental period, through which most of the ENS development occurs, is highly susceptible to microenvironmental perturbation. Over the past decade, accumulating evidence has shown the impact of stress and early life adversity (ELA) on host gastrointestinal pathophysiology. While most of the focus has been on alterations in brain structure and function, limited experimental work in rodents suggest that the enteric nervous system can also be directly affected, as shown by changes in the number, phenotype, and reactivity of enteric nerves. The work of Medland et al. in the current issue of this journal demonstrates that such alterations also occur in pigs, a larger mammalian species with high translational value to human. This work also highlights a sex-differential susceptibility of the ENS to the effect of ELA, which could contribute to the higher prevalence of GI disorders in women. In this mini-review, we will discuss the development and composition of the ENS and related gastrointestinal sensory motor and secretory functions. We will then focus on the influence of stress on the enteric nervous system, with a particular emphasis on neurodevelopmental changes. Finally, we will discuss the influence of sex on those parameters. PMID:27561694

  5. Metal toxicity in the central nervous system

    SciTech Connect

    Clarkson, T.W.

    1987-11-01

    The nervous system is the principal target for a number of metals. The alkyl derivatives of certain metals-lead, mercury and tin-are specially neurotoxic. Concern over human exposure and in some cases, outbreaks of poisoning, have stimulated research into the toxic action of these metals. A number of interesting hypotheses have been proposed for the mechanism of lead toxicity on the nervous system. Lead is know to be a potent inhibitor of heme synthesis. A reduction in heme-containing enzymes could compromise energy metabolism. Lead may affect brain function by interference with neurotransmitters such as ..gamma..-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and binding of calcium ions. Methylmercury produces focal damage to specific areas in the adult brain. One hypothesis proposes that certain cells are susceptible because they cannot repair the initial damage to the protein synthesis machinery. The developing nervous system is especially susceptible to damage by methylmercury. It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages.

  6. Comparative anatomy of the autonomic nervous system.

    PubMed

    Nilsson, Stefan

    2011-11-16

    This short review aims to point out the general anatomical features of the autonomic nervous systems of non-mammalian vertebrates. In addition it attempts to outline the similarities and also the increased complexity of the autonomic nervous patterns from fish to tetrapods. With the possible exception of the cyclostomes, perhaps the most striking feature of the vertebrate autonomic nervous system is the similarity between the vertebrate classes. An evolution of the complexity of the system can be seen, with the segmental ganglia of elasmobranchs incompletely connected longitudinally, while well developed paired sympathetic chains are present in teleosts and the tetrapods. In some groups the sympathetic chains may be reduced (dipnoans and caecilians), and have yet to be properly described in snakes. Cranial autonomic pathways are present in the oculomotor (III) and vagus (X) nerves of gnathostome fish and the tetrapods, and with the evolution of salivary and lachrymal glands in the tetrapods, also in the facial (VII) and glossopharyngeal (IX) nerves. PMID:20444653

  7. The molecular physiology of the axo-myelinic synapse.

    PubMed

    Micu, Ileana; Plemel, Jason R; Lachance, Celia; Proft, Juliane; Jansen, Andrew J; Cummins, Karen; van Minnen, Jan; Stys, Peter K

    2016-02-01

    Myelinated axons efficiently transmit information over long distances. The apposed myelin sheath confers favorable electrical properties, but restricts access of the axon to its extracellular milieu. Therefore, axonal metabolic support may require specific axo-myelinic communication. Here we explored activity-dependent glutamate-mediated signaling from axon to myelin. 2-Photon microscopy was used to image Ca(2+) changes in myelin in response to electrical stimulation of optic nerve axons ex vivo. We show that optic nerve myelin responds to axonal action potentials by a rise in Ca(2+) levels mediated by GluN2D and GluN3A-containing NMDA receptors. Glutamate is released from axons in a vesicular manner that is tetanus toxin-sensitive. The Ca(2+) source for vesicular fusion is provided by ryanodine receptors on axonal Ca(2+) stores, controlled by L-type Ca(2+) channels that sense depolarization of the internodal axolemma. Genetic ablation of GluN2D and GluN3A subunits results in greater lability of the compact myelin. Our results support the existence of a novel synapse between the axon and its myelin, suggesting a means by which traversing action potentials can signal the overlying myelin sheath. This may be an important physiological mechanism by which an axon can signal companion glia for metabolic support or adjust properties of its myelin in a dynamic manner. The axo-myelinic synapse may contribute to learning, while its disturbances may play a role in the pathophysiology of central nervous system disorders such as schizophrenia, where subtle abnormalities of myelinated white matter tracts have been shown in the human, or to frank demyelinating disorders such as multiple sclerosis.

  8. MHC-I and PirB Upregulation in the Central and Peripheral Nervous System following Sciatic Nerve Injury.

    PubMed

    Bombeiro, André Luis; Thomé, Rodolfo; Oliveira Nunes, Sérgio Luiz; Monteiro Moreira, Bárbara; Verinaud, Liana; Oliveira, Alexandre Leite Rodrigues de

    2016-01-01

    Major histocompatibility complex class one (MHC-I) antigen-presenting molecules participate in central nervous system (CNS) synaptic plasticity, as does the paired immunoglobulin-like receptor B (PirB), an MHC-I ligand that can inhibit immune-cells and bind to myelin axon growth inhibitors. Based on the dual roles of both molecules in the immune and nervous systems, we evaluated their expression in the central and peripheral nervous system (PNS) following sciatic nerve injury in mice. Increased PirB and MHC-I protein and gene expression is present in the spinal cord one week after nerve transection, PirB being mostly expressed in the neuropile region. In the crushed nerve, MHC-I protein levels increased 2 weeks after lesion (wal) and progressively decreased over the next eight weeks. The same kinetics were observed for infiltrating cytotoxic T lymphocytes (CTLs) but not for PirB expression, which continuously increased. Both MHC-I and PirB were found in macrophages and Schwann cells but rarely in axons. Interestingly, at 8 wal, PirB was mainly restricted to the myelin sheath. Our findings reinforce the participation of MHC-I and PirB in CNS plasticity events. In contrast, opposing expression levels of these molecules were found in the PNS, so that MHC-I and PirB seem to be mostly implicated in antigen presentation to CTLs and axon myelination, respectively. PMID:27551751

  9. MHC-I and PirB Upregulation in the Central and Peripheral Nervous System following Sciatic Nerve Injury

    PubMed Central

    Bombeiro, André Luis; Thomé, Rodolfo; Oliveira Nunes, Sérgio Luiz; Monteiro Moreira, Bárbara; Verinaud, Liana; de Oliveira, Alexandre Leite Rodrigues

    2016-01-01

    Major histocompatibility complex class one (MHC-I) antigen-presenting molecules participate in central nervous system (CNS) synaptic plasticity, as does the paired immunoglobulin-like receptor B (PirB), an MHC-I ligand that can inhibit immune-cells and bind to myelin axon growth inhibitors. Based on the dual roles of both molecules in the immune and nervous systems, we evaluated their expression in the central and peripheral nervous system (PNS) following sciatic nerve injury in mice. Increased PirB and MHC-I protein and gene expression is present in the spinal cord one week after nerve transection, PirB being mostly expressed in the neuropile region. In the crushed nerve, MHC-I protein levels increased 2 weeks after lesion (wal) and progressively decreased over the next eight weeks. The same kinetics were observed for infiltrating cytotoxic T lymphocytes (CTLs) but not for PirB expression, which continuously increased. Both MHC-I and PirB were found in macrophages and Schwann cells but rarely in axons. Interestingly, at 8 wal, PirB was mainly restricted to the myelin sheath. Our findings reinforce the participation of MHC-I and PirB in CNS plasticity events. In contrast, opposing expression levels of these molecules were found in the PNS, so that MHC-I and PirB seem to be mostly implicated in antigen presentation to CTLs and axon myelination, respectively. PMID:27551751

  10. Classical Neurotransmitters and their Significance within the Nervous System.

    ERIC Educational Resources Information Center

    Veca, A.; Dreisbach, J. H.

    1988-01-01

    Describes some of the chemical compounds involved in the nervous system and their roles in transmitting nerve signals. Discusses acetylcholine, dopamine, norepinephrine, serotonin, histamine, glycine, glutemate, and gamma-aminobutyric acid and their effects within the nervous system. (CW)

  11. What Are the Parts of the Nervous System?

    MedlinePlus

    ... Research Planning Scientific Resources Research A-Z Topics Neuroscience Overview Condition Information Parts of the nervous system ... functions does the nervous system control? Why study neuroscience? What are the areas of neuroscience? NICHD Research ...

  12. Towards resolving the transcription factor network controlling myelin gene expression

    PubMed Central

    Fulton, Debra L.; Denarier, Eric; Friedman, Hana C.; Wasserman, Wyeth W.; Peterson, Alan C.

    2011-01-01

    In the central nervous system (CNS), myelin is produced from spirally-wrapped oligodendrocyte plasma membrane and, as exemplified by the debilitating effects of inherited or acquired myelin abnormalities in diseases such as multiple sclerosis, it plays a critical role in nervous system function. Myelin sheath production coincides with rapid up-regulation of numerous genes. The complexity of their subsequent expression patterns, along with recently recognized heterogeneity within the oligodendrocyte lineage, suggest that the regulatory networks controlling such genes drive multiple context-specific transcriptional programs. Conferring this nuanced level of control likely involves a large repertoire of interacting transcription factors (TFs). Here, we combined novel strategies of computational sequence analyses with in vivo functional analysis to establish a TF network model of coordinate myelin-associated gene transcription. Notably, the network model captures regulatory DNA elements and TFs known to regulate oligodendrocyte myelin gene transcription and/or oligodendrocyte development, thereby validating our approach. Further, it links to numerous TFs with previously unsuspected roles in CNS myelination and suggests collaborative relationships amongst both known and novel TFs, thus providing deeper insight into the myelin gene transcriptional network. PMID:21729871

  13. The BIRN Project: Imaging the Nervous System

    SciTech Connect

    Ellisman, Mark

    2006-05-22

    The grand goal in neuroscience research is to understand how the interplay of structural, chemical and electrical signals in nervous tissue gives rise to behavior. Experimental advances of the past decades have given the individual neuroscientist an increasingly powerful arsenal for obtaining data, from the level of molecules to nervous systems. Scientists have begun the arduous and challenging process of adapting and assembling neuroscience data at all scales of resolution and across disciplines into computerized databases and other easily accessed sources. These databases will complement the vast structural and sequence databases created to catalogue, organize and analyze gene sequences and protein products. The general premise of the neuroscience goal is simple; namely that with "complete" knowledge of the genome and protein structures accruing rapidly we next need to assemble an infrastructure that will facilitate acquisition of an understanding for how functional complexes operate in their cell and tissue contexts.

  14. The BIRN Project: Imaging the Nervous System

    SciTech Connect

    Ellisman, Mark

    2006-05-22

    The grand goal in neuroscience research is to understand how the interplay of structural, chemical and electrical signals in nervous tissue gives rise to behavior. Experimental advances of the past decades have given the individual neuroscientist an increasingly powerful arsenal for obtaining data, from the level of molecules to nervous systems. Scientists have begun the arduous and challenging process of adapting and assembling neuroscience data at all scales of resolution and across disciplines into computerized databases and other easily accessed sources. These databases will complement the vast structural and sequence databases created to catalogue, organize and analyze gene sequences and protein products. The general premise of the neuroscience goal is simple; namely that with 'complete' knowledge of the genome and protein structures accruing rapidly we next need to assemble an infrastructure that will facilitate acquisition of an understanding for how functional complexes operate in their cell and tissue contexts.

  15. Lysophosphatidic Acid signaling in the nervous system.

    PubMed

    Yung, Yun C; Stoddard, Nicole C; Mirendil, Hope; Chun, Jerold

    2015-02-18

    The brain is composed of many lipids with varied forms that serve not only as structural components but also as essential signaling molecules. Lysophosphatidic acid (LPA) is an important bioactive lipid species that is part of the lysophospholipid (LP) family. LPA is primarily derived from membrane phospholipids and signals through six cognate G protein-coupled receptors (GPCRs), LPA1-6. These receptors are expressed on most cell types within central and peripheral nervous tissues and have been functionally linked to many neural processes and pathways. This Review covers a current understanding of LPA signaling in the nervous system, with particular focus on the relevance of LPA to both physiological and diseased states. PMID:25695267

  16. Phase separation of myelin proteins in triton X-114: differential behavior of myelin basic protein in purified myelin and in cultured oligodendrocytes.

    PubMed

    Bürgisser, P; Matthieu, J M

    1989-01-01

    Rabbit central (CNS) and peripheral nervous system (PNS) myelin, as well as nonmyelinating pig oligodendrocytes in culture, were extracted at 0-4 degrees C with the nonionic detergent Triton X-114. The solubilized proteins were partitioned into the detergent-rich and detergent-depleted (aqueous) phases that form upon heating to 37 degrees C. The proteolipid protein (PLP), myelin-associated glycoprotein (MAG), myelin oligodendrocyte glycoprotein (MOG) and P0 extracted from myelin were found exclusively in the detergent phase which is characteristic of the intrinsic membrane proteins. This was also the case for Wolfgram protein (WP), although this protein lacks transmembrane domains. A small fraction of the MAG and MOG extracted from oligodendrocytes partitioned into the aqueous phase, suggesting an altered conformation outside myelin or a different state of glycosylation. P2 and myelin basic protein (MBP) showed distinct patterns of behavior. P2 was found mainly in the aqueous phase giving strong support to its theoretically predicted conformation. Eighty-nine percent of the MBP extracted from CNS myelin and 81% of the pure MBP partitioned into the detergent phase. Surprisingly, most of the MBP extracted from the oligodendrocytes was recovered in the aqueous phase. We speculate that, in these cells, a hydrophilic protein might bind to the MBP in a specific manner, thereby preventing it from binding inappropriately to cellular components before its insertion into myelin.

  17. Neuroimaging in Central Nervous System Lymphoma.

    PubMed

    Nabavizadeh, Seyed Ali; Vossough, Arastoo; Hajmomenian, Mehrdad; Assadsangabi, Reza; Mohan, Suyash

    2016-08-01

    Primary central nervous system lymphoma (PCNSL) is a rare aggressive high-grade type of extranodal lymphoma. PCNSL can have a variable imaging appearance and can mimic other brain disorders such as encephalitis, demyelination, and stroke. In addition to PCNSL, the CNS can be secondarily involved by systemic lymphoma. Computed tomography and conventional MRI are the initial imaging modalities to evaluate these lesions. Recently, however, advanced MRI techniques are more often used in an effort to narrow the differential diagnosis and potentially inform diagnostic and therapeutic decisions. PMID:27443998

  18. Viral diseases of the central nervous system.

    PubMed

    Swanson, Phillip A; McGavern, Dorian B

    2015-04-01

    Virus-induced diseases of the central nervous system (CNS) represent a significant burden to human health worldwide. The complexity of these diseases is influenced by the sheer number of different neurotropic viruses, the diverse routes of CNS entry, viral tropism, and the immune system. Using a combination of human pathological data and experimental animal models, we have begun to uncover many of the mechanisms that viruses use to enter the CNS and cause disease. This review highlights a selection of neurotropic viruses that infect the CNS and explores the means by which they induce neurological diseases such as meningitis, encephalitis, and myelitis.

  19. Surgery of the sympathetic nervous system.

    PubMed

    Lee, B Y; Da Silva, M C; Aquino-Chu, G; Herz, B L

    1996-01-01

    This article reviews the innervation of the arterial system of the lower extremity, lumbar sympathectomy in vascular surgery, lumbar sympathectomy for digital gangrene and in the prevention of major amputation of the lower extremity and substance P's role in neurogenic inflammatory modulation. Long-term results of lumbar sympathectomy and direct arterial bypass surgery have also been reviewed. In addition to the pilomotor, sudomotor and vasomotor actions of the sympathetic nervous system via its neurotransmitters, the molecular basis of the chronic neurogenic inflammatory reaction have been addressed with special attention to the discovery of substance P in the lumbar sympathetic chain and ganglia of human beings.

  20. Atopic dermatitis and the nervous system.

    PubMed

    Misery, Laurent

    2011-12-01

    Due to the narrow associations between the skin, immune system, and nervous system, nerve endings are very important in the pathophysiology of inflammatory dermatoses and especially in atopic dermatitis. Many neurotransmitters and nerve growth factors that are released in blood or skin are involved in neurogenic inflammation, which dramatically enhance the inflammation induced by immune cells. During times of stress, their release is highly enhanced. In atopic dermatitis lesions, there are many specific changes in skin neurobiology and neurophysiology. These interesting data suggest that novel therapeutic possibilities can be imagined.

  1. The myelin oligodendrocyte glycoprotein directly binds nerve growth factor to modulate central axon circuitry.

    PubMed

    von Büdingen, H-Christian; Mei, Feng; Greenfield, Ariele; Jahn, Sarah; Shen, Yun-An A; Reid, Hugh H; McKemy, David D; Chan, Jonah R

    2015-09-14

    Myelin oligodendrocyte glycoprotein (MOG) is a central nervous system myelin-specific molecule expressed on the outer lamellae of myelin. To date, the exact function of MOG has remained unknown, with MOG knockout mice displaying normal myelin ultrastructure and no apparent specific phenotype. In this paper, we identify nerve growth factor (NGF) as a binding partner for MOG and demonstrate that this interaction is capable of sequestering NGF from TrkA-expressing neurons to modulate axon growth and survival. Deletion of MOG results in aberrant sprouting of nociceptive neurons in the spinal cord. Binding of NGF to MOG may offer widespread implications into mechanisms that underlie pain pathways.

  2. Axon growth inhibition by RhoA/ROCK in the central nervous system

    PubMed Central

    Fujita, Yuki; Yamashita, Toshihide

    2014-01-01

    Rho kinase (ROCK) is a serine/threonine kinase and a downstream target of the small GTPase Rho. The RhoA/ROCK pathway is associated with various neuronal functions such as migration, dendrite development, and axonal extension. Evidence from animal studies reveals that RhoA/ROCK signaling is involved in various central nervous system (CNS) diseases, including optic nerve and spinal cord injuries, stroke, and neurodegenerative diseases. Given that RhoA/ROCK plays a critical role in the pathophysiology of CNS diseases, the development of therapeutic agents targeting this pathway is expected to contribute to the treatment of CNS diseases. The RhoA/ROCK pathway mediates the effects of myelin-associated axon growth inhibitors—Nogo, myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and repulsive guidance molecule (RGM). Blocking RhoA/ROCK signaling can reverse the inhibitory effects of these molecules on axon outgrowth, and promotes axonal sprouting and functional recovery in animal models of CNS injury. To date, several RhoA/ROCK inhibitors have been under development or in clinical trials as therapeutic agents for neurological disorders. In this review, we focus on the RhoA/ROCK signaling pathway in neurological disorders. We also discuss the potential therapeutic approaches of RhoA/ROCK inhibitors for various neurological disorders. PMID:25374504

  3. Axon growth inhibition by RhoA/ROCK in the central nervous system.

    PubMed

    Fujita, Yuki; Yamashita, Toshihide

    2014-01-01

    Rho kinase (ROCK) is a serine/threonine kinase and a downstream target of the small GTPase Rho. The RhoA/ROCK pathway is associated with various neuronal functions such as migration, dendrite development, and axonal extension. Evidence from animal studies reveals that RhoA/ROCK signaling is involved in various central nervous system (CNS) diseases, including optic nerve and spinal cord injuries, stroke, and neurodegenerative diseases. Given that RhoA/ROCK plays a critical role in the pathophysiology of CNS diseases, the development of therapeutic agents targeting this pathway is expected to contribute to the treatment of CNS diseases. The RhoA/ROCK pathway mediates the effects of myelin-associated axon growth inhibitors-Nogo, myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and repulsive guidance molecule (RGM). Blocking RhoA/ROCK signaling can reverse the inhibitory effects of these molecules on axon outgrowth, and promotes axonal sprouting and functional recovery in animal models of CNS injury. To date, several RhoA/ROCK inhibitors have been under development or in clinical trials as therapeutic agents for neurological disorders. In this review, we focus on the RhoA/ROCK signaling pathway in neurological disorders. We also discuss the potential therapeutic approaches of RhoA/ROCK inhibitors for various neurological disorders.

  4. Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system.

    PubMed

    Gonzalez, Ginez A; Hofer, Matthias P; Syed, Yasir A; Amaral, Ana I; Rundle, Jon; Rahman, Saifur; Zhao, Chao; Kotter, Mark R N

    2016-01-01

    Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID:27554391

  5. Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system

    PubMed Central

    Gonzalez, Ginez A.; Hofer, Matthias P.; Syed, Yasir A.; Amaral, Ana I.; Rundle, Jon; Rahman, Saifur; Zhao, Chao; Kotter, Mark R. N.

    2016-01-01

    Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID:27554391

  6. Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination.

    PubMed

    Miyamoto, Yuki; Torii, Tomohiro; Takada, Shuji; Ohno, Nobuhiko; Saitoh, Yurika; Nakamura, Kazuaki; Ito, Akihito; Ogata, Toru; Terada, Nobuo; Tanoue, Akito; Yamauchi, Junji

    2015-10-01

    During early development of the peripheral nervous system, Schwann cell precursors proliferate, migrate, and differentiate into premyelinating Schwann cells. After birth, Schwann cells envelop neuronal axons with myelin sheaths. Although some molecular mechanisms underlying myelination by Schwann cells have been identified, the whole picture remains unclear. Here we show that signaling through Tyro3 receptor tyrosine kinase and its binding partner, Fyn nonreceptor cytoplasmic tyrosine kinase, is involved in myelination by Schwann cells. Impaired formation of myelin segments is observed in Schwann cell neuronal cultures established from Tyro3-knockout mouse dorsal root ganglia (DRG). Indeed, Tyro3-knockout mice exhibit reduced myelin thickness. By affinity chromatography, Fyn was identified as the binding partner of the Tyro3 intracellular domain, and activity of Fyn is down-regulated in Tyro3-knockout mice, suggesting that Tyro3, acting through Fyn, regulates myelination. Ablating Fyn in mice results in reduced myelin thickness. Decreased myelin formation is observed in cultures established from Fyn-knockout mouse DRG. Furthermore, decreased kinase activity levels and altered expression of myelination-associated transcription factors are observed in these knockout mice. These results suggest the involvement of Tyro3 receptor and its binding partner Fyn in Schwann cell myelination. This constitutes a newly recognized receptor-linked signaling mechanism that can control Schwann cell myelination.

  7. Formation of compact myelin is required for maturation of the axonal cytoskeleton

    NASA Technical Reports Server (NTRS)

    Brady, S. T.; Witt, A. S.; Kirkpatrick, L. L.; de Waegh, S. M.; Readhead, C.; Tu, P. H.; Lee, V. M.

    1999-01-01

    Although traditional roles ascribed to myelinating glial cells are structural and supportive, the importance of compact myelin for proper functioning of the nervous system can be inferred from mutations in myelin proteins and neuropathologies associated with loss of myelin. Myelinating Schwann cells are known to affect local properties of peripheral axons (de Waegh et al., 1992), but little is known about effects of oligodendrocytes on CNS axons. The shiverer mutant mouse has a deletion in the myelin basic protein gene that eliminates compact myelin in the CNS. In shiverer mice, both local axonal features like phosphorylation of cytoskeletal proteins and neuronal perikaryon functions like cytoskeletal gene expression are altered. This leads to changes in the organization and composition of the axonal cytoskeleton in shiverer unmyelinated axons relative to age-matched wild-type myelinated fibers, although connectivity and patterns of neuronal activity are comparable. Remarkably, transgenic shiverer mice with thin myelin sheaths display an intermediate phenotype indicating that CNS neurons are sensitive to myelin sheath thickness. These results indicate that formation of a normal compact myelin sheath is required for normal maturation of the neuronal cytoskeleton in large CNS neurons.

  8. The central nervous system of ascidian larvae.

    PubMed

    Hudson, Clare

    2016-09-01

    Ascidians are marine invertebrate chordates. Their tadpole larvae contain a dorsal tubular nervous system, resulting from the rolling up of a neural plate. Along the anterior-posterior (A-P) axis, the central nervous system (CNS) is organized into a sensory vesicle, neck, trunk ganglion, and tail nerve cord and consists of approximately only 330 cells, of which around 100 are thought to be neurons. The organization of distinct neuronal cell types and neurotransmitter gene expression within the CNS has been described. The unique developmental mode of ascidians, with a small number of cells and a fixed cell division pattern, allows individual cells to be traced throughout development. This feature has led to the complete documentation of the cell lineages of certain cell types in the CNS. Thus, a step-by-step understanding of nervous system development from the initial stages of neural induction to the neurogenesis of individual neurons is a feasible goal. The genetic control of neural fate induction and early neural plate patterning are now well understood. The molecular mechanisms specifying the cholinergic neurons of the trunk ganglion as well as the pigment cells of the sensory organs are also well elucidated. In addition, studies have begun on the morphogenetic processes of neurulation. Remaining challenges include building an embryonic atlas integrating gene expression patterns, cell lineage, and neuronal cell types as well as developing the gene regulatory networks of cell fate specification and integrating them with the genetic control of morphogenesis. WIREs Dev Biol 2016, 5:538-561. doi: 10.1002/wdev.239 For further resources related to this article, please visit the WIREs website. PMID:27328318

  9. Histoplasmosis of the central nervous system.

    PubMed Central

    Tan, V; Wilkins, P; Badve, S; Coppen, M; Lucas, S; Hay, R; Schon, F

    1992-01-01

    Histoplasma capsulatum infection of the central nervous system is extremely rare in the United Kingdom partly because the organism is not endemic. However, because the organism can remain quiescent in the lungs or the adrenal glands for over 40 years before dissemination, it increasingly needs to be considered in unexplained neurological disease particularly in people who lived in endemic areas as children. In this paper a rapidly progressive fatal myelopathy in an English man brought up in India was shown at necropsy to be due to histoplasmosis. The neurological features of this infection are reviewed. Images PMID:1640242

  10. Central nervous system involvement in diabetes mellitus.

    PubMed

    Selvarajah, Dinesh; Tesfaye, Solomon

    2006-12-01

    Diabetic complications result in much morbidity and mortality and considerable consumption of scarce medical resources. Thus, elucidation of the risk factors and pathophysiologic mechanisms underlying diabetic complications is important. The effects of diabetes on the central nervous system (CNS) result in cognitive dysfunction and cerebrovascular disease. Treatment-related hypoglycemia also has CNS consequences. Advances in neuroimaging now provide greater insights into the structural and functional impact of diabetes on the CNS. Greater understanding of CNS involvement could lead to new strategies to prevent or reverse the damage caused by diabetes mellitus.

  11. Mold Infections of the Central Nervous System

    PubMed Central

    McCarthy, Matthew; Rosengart, Axel; Schuetz, Audrey N.; Kontoyiannis, Dimitrios P.; Walsh, Thomas J.

    2016-01-01

    The recent outbreak of exserohilum rostratum meningitis linked to epidural injections of methylprednisolone acetate has brought renewed attention to mold infections of the central nervous system (CNS).1 Although uncommon, these infections are often devastating and difficult to treat. This focused review of the epidemiologic aspects, clinical characteristics, and treatment of mold infections of the CNS covers a group of common pathogens: aspergillus, fusarium, and scedosporium species, molds in the order Mucorales, and dematiaceous molds. Infections caused by these pathogen groups have distinctive epidemiologic profiles, clinical manifestations, microbiologic characteristics, and therapeutic implications, all of which clinicians should understand. PMID:25006721

  12. Did the ctenophore nervous system evolve independently?

    PubMed

    Ryan, Joseph F

    2014-08-01

    Recent evidence supports the placement of ctenophores as the most distant relative to all other animals. This revised animal tree means that either the ancestor of all animals possessed neurons (and that sponges and placozoans apparently lost them) or that ctenophores developed them independently. Differentiating between these possibilities is important not only from a historical perspective, but also for the interpretation of a wide range of neurobiological results. In this short perspective paper, I review the evidence in support of each scenario and show that the relationship between the nervous system of ctenophores and other animals is an unsolved, yet tractable problem. PMID:24986234

  13. Physiology of the Autonomic Nervous System

    PubMed Central

    2007-01-01

    This manuscript discusses the physiology of the autonomic nervous system (ANS). The following topics are presented: regulation of activity; efferent pathways; sympathetic and parasympathetic divisions; neurotransmitters, their receptors and the termination of their activity; functions of the ANS; and the adrenal medullae. In addition, the application of this material to the practice of pharmacy is of special interest. Two case studies regarding insecticide poisoning and pheochromocytoma are included. The ANS and the accompanying case studies are discussed over 5 lectures and 2 recitation sections during a 2-semester course in Human Physiology. The students are in the first-professional year of the doctor of pharmacy program. PMID:17786266

  14. Vascularisation of the central nervous system

    PubMed Central

    Tata, Mathew; Ruhrberg, Christiana; Fantin, Alessandro

    2015-01-01

    The developing central nervous system (CNS) is vascularised through the angiogenic invasion of blood vessels from a perineural vascular plexus, followed by continued sprouting and remodelling until a hierarchical vascular network is formed. Remarkably, vascularisation occurs without perturbing the intricate architecture of the neurogenic niches or the emerging neural networks. We discuss the mouse hindbrain, forebrain and retina as widely used models to study developmental angiogenesis in the mammalian CNS and provide an overview of key cellular and molecular mechanisms regulating the vascularisation of these organs. PMID:26222953

  15. Did the ctenophore nervous system evolve independently?

    PubMed

    Ryan, Joseph F

    2014-08-01

    Recent evidence supports the placement of ctenophores as the most distant relative to all other animals. This revised animal tree means that either the ancestor of all animals possessed neurons (and that sponges and placozoans apparently lost them) or that ctenophores developed them independently. Differentiating between these possibilities is important not only from a historical perspective, but also for the interpretation of a wide range of neurobiological results. In this short perspective paper, I review the evidence in support of each scenario and show that the relationship between the nervous system of ctenophores and other animals is an unsolved, yet tractable problem.

  16. [Sports injuries of the nervous system].

    PubMed

    Lang, C; Stefan, H

    1999-08-01

    Almost 1% of all Germans suffer sports injuries each year, almost 5% of all peripheral nerve lesions are due to sports. A review is given on various activities detailing the specific risks for traumata of the central and peripheral nervous system. Specifically these are volleyball, handball, basketball, American football, soccer, bowling, hockey, baseball, tennis, golf, javelin, fencing, wrestling, judo, boxing, running, jumping, dancing, mountain climbing, weight lifting, gymnastics, horse-back riding, swimming, rowing, skiing, skating, shooting, (motor) biking, car racing, flying, and sports for the disabled. The knowledge of typical traumata should enable the neurologist to rapidly and reliably recognize related lesions and to contribute to their prevention or improvement.

  17. Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP.

    PubMed

    Hu, Bo; Arpag, Sezgi; Zhang, Xuebao; Möbius, Wiebke; Werner, Hauke; Sosinsky, Gina; Ellisman, Mark; Zhang, Yang; Hamilton, Audra; Chernoff, Jonathan; Li, Jun

    2016-09-01

    Schwann cells in the peripheral nervous systems extend their membranes to wrap axons concentrically and form the insulating sheath, called myelin. The spaces between layers of myelin are sealed by myelin junctions. This tight insulation enables rapid conduction of electric impulses (action potentials) through axons. Demyelination (stripping off the insulating sheath) has been widely regarded as one of the most important mechanisms altering the action potential propagation in many neurological diseases. However, the effective nerve conduction is also thought to require a proper myelin seal through myelin junctions such as tight junctions and adherens junctions. In the present study, we have demonstrated the disruption of myelin junctions in a mouse model (Pmp22+/-) of hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of Pmp22 gene. We observed a robust increase of F-actin in Pmp22+/- nerve regions where myelin junctions were disrupted, leading to increased myelin permeability. These abnormalities were present long before segmental demyelination at the late phase of Pmp22+/- mice. Moreover, the increase of F-actin levels correlated with an enhanced activity of p21-activated kinase (PAK1), a molecule known to regulate actin polymerization. Pharmacological inhibition of PAK normalized levels of F-actin, and completely prevented the progression of the myelin junction disruption and nerve conduction failure in Pmp22+/- mice. Our findings explain how abnormal myelin permeability is caused in HNPP, leading to impaired action potential propagation in the absence of demyelination. We call it "functional demyelination", a novel mechanism upstream to the actual stripping of myelin that is relevant to many demyelinating diseases. This observation also provides a potential therapeutic approach for HNPP.

  18. Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP

    PubMed Central

    Hu, Bo; Zhang, Xuebao; Möbius, Wiebke; Werner, Hauke; Sosinsky, Gina; Ellisman, Mark; Zhang, Yang; Hamilton, Audra; Chernoff, Jonathan; Li, Jun

    2016-01-01

    Schwann cells in the peripheral nervous systems extend their membranes to wrap axons concentrically and form the insulating sheath, called myelin. The spaces between layers of myelin are sealed by myelin junctions. This tight insulation enables rapid conduction of electric impulses (action potentials) through axons. Demyelination (stripping off the insulating sheath) has been widely regarded as one of the most important mechanisms altering the action potential propagation in many neurological diseases. However, the effective nerve conduction is also thought to require a proper myelin seal through myelin junctions such as tight junctions and adherens junctions. In the present study, we have demonstrated the disruption of myelin junctions in a mouse model (Pmp22+/-) of hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of Pmp22 gene. We observed a robust increase of F-actin in Pmp22+/- nerve regions where myelin junctions were disrupted, leading to increased myelin permeability. These abnormalities were present long before segmental demyelination at the late phase of Pmp22+/- mice. Moreover, the increase of F-actin levels correlated with an enhanced activity of p21-activated kinase (PAK1), a molecule known to regulate actin polymerization. Pharmacological inhibition of PAK normalized levels of F-actin, and completely prevented the progression of the myelin junction disruption and nerve conduction failure in Pmp22+/- mice. Our findings explain how abnormal myelin permeability is caused in HNPP, leading to impaired action potential propagation in the absence of demyelination. We call it “functional demyelination”, a novel mechanism upstream to the actual stripping of myelin that is relevant to many demyelinating diseases. This observation also provides a potential therapeutic approach for HNPP. PMID:27583434

  19. Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP.

    PubMed

    Hu, Bo; Arpag, Sezgi; Zhang, Xuebao; Möbius, Wiebke; Werner, Hauke; Sosinsky, Gina; Ellisman, Mark; Zhang, Yang; Hamilton, Audra; Chernoff, Jonathan; Li, Jun

    2016-09-01

    Schwann cells in the peripheral nervous systems extend their membranes to wrap axons concentrically and form the insulating sheath, called myelin. The spaces between layers of myelin are sealed by myelin junctions. This tight insulation enables rapid conduction of electric impulses (action potentials) through axons. Demyelination (stripping off the insulating sheath) has been widely regarded as one of the most important mechanisms altering the action potential propagation in many neurological diseases. However, the effective nerve conduction is also thought to require a proper myelin seal through myelin junctions such as tight junctions and adherens junctions. In the present study, we have demonstrated the disruption of myelin junctions in a mouse model (Pmp22+/-) of hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of Pmp22 gene. We observed a robust increase of F-actin in Pmp22+/- nerve regions where myelin junctions were disrupted, leading to increased myelin permeability. These abnormalities were present long before segmental demyelination at the late phase of Pmp22+/- mice. Moreover, the increase of F-actin levels correlated with an enhanced activity of p21-activated kinase (PAK1), a molecule known to regulate actin polymerization. Pharmacological inhibition of PAK normalized levels of F-actin, and completely prevented the progression of the myelin junction disruption and nerve conduction failure in Pmp22+/- mice. Our findings explain how abnormal myelin permeability is caused in HNPP, leading to impaired action potential propagation in the absence of demyelination. We call it "functional demyelination", a novel mechanism upstream to the actual stripping of myelin that is relevant to many demyelinating diseases. This observation also provides a potential therapeutic approach for HNPP. PMID:27583434

  20. Laboratory Diagnosis of Central Nervous System Infection.

    PubMed

    He, Taojun; Kaplan, Samuel; Kamboj, Mini; Tang, Yi-Wei

    2016-11-01

    Central nervous system (CNS) infections are potentially life threatening if not diagnosed and treated early. The initial clinical presentations of many CNS infections are non-specific, making a definitive etiologic diagnosis challenging. Nucleic acid in vitro amplification-based molecular methods are increasingly being applied for routine microbial detection. These methods are a vast improvement over conventional techniques with the advantage of rapid turnaround and higher sensitivity and specificity. Additionally, molecular methods performed on cerebrospinal fluid samples are considered the new gold standard for diagnosis of CNS infection caused by pathogens, which are otherwise difficult to detect. Commercial diagnostic platforms offer various monoplex and multiplex PCR assays for convenient testing of targets that cause similar clinical illness. Pan-omic molecular platforms possess potential for use in this area. Although molecular methods are predicted to be widely used in diagnosing and monitoring CNS infections, results generated by these methods need to be carefully interpreted in combination with clinical findings. This review summarizes the currently available armamentarium of molecular assays for diagnosis of central nervous system infections, their application, and future approaches. PMID:27686677

  1. Central nervous system toxicity of metallic nanoparticles

    PubMed Central

    Feng, Xiaoli; Chen, Aijie; Zhang, Yanli; Wang, Jianfeng; Shao, Longquan; Wei, Limin

    2015-01-01

    Nanomaterials (NMs) are increasingly used for the therapy, diagnosis, and monitoring of disease- or drug-induced mechanisms in the human biological system. In view of their small size, after certain modifications, NMs have the capacity to bypass or cross the blood–brain barrier. Nanotechnology is particularly advantageous in the field of neurology. Examples may include the utilization of nanoparticle (NP)-based drug carriers to readily cross the blood–brain barrier to treat central nervous system (CNS) diseases, nanoscaffolds for axonal regeneration, nanoelectromechanical systems in neurological operations, and NPs in molecular imaging and CNS imaging. However, NPs can also be potentially hazardous to the CNS in terms of nano-neurotoxicity via several possible mechanisms, such as oxidative stress, autophagy, and lysosome dysfunction, and the activation of certain signaling pathways. In this review, we discuss the dual effect of NMs on the CNS and the mechanisms involved. The limitations of the current research are also discussed. PMID:26170667

  2. High-resolution fluorescence microscopy of myelin without exogenous probes.

    PubMed

    Christensen, Pia Crone; Brideau, Craig; Poon, Kelvin W C; Döring, Axinia; Yong, V Wee; Stys, Peter K

    2014-02-15

    Myelin is a critical element of the central and peripheral nervous systems of all higher vertebrates. Any disturbance in the integrity of the myelin sheath interferes with the axon's ability to conduct action potentials. Thus, the study of myelin structure and biochemistry is critically important. Accurate and even staining of myelin is often difficult because of its lipid-rich nature and multiple tight membrane wraps, hindering penetration of immunoprobes. Here we show a method of visualizing myelin that is fast, inexpensive and reliable using the cross-linking fixative glutaraldehyde that produces strong, broad-spectrum auto-fluorescence in fixed tissue. Traditionally, effort is generally aimed at eliminating this auto-fluorescence. However, we show that this intrinsic signal, which is very photostable and particularly strong in glutaraldehyde-fixed myelin, can be exploited to visualize this structure to produce very detailed images of myelin morphology. We imaged fixed rodent tissues from the central and peripheral nervous systems using spectral confocal microscopy to acquire high-resolution 3-dimensional images spanning the visual range of wavelengths (400-750 nm). Mathematical post-processing allows accurate and unequivocal separation of broadband auto-fluorescence from exogenous fluorescent probes such as DAPI and fluorescently-tagged secondary antibodies. We additionally show the feasibility of immunohistochemistry with antigen retrieval, which allows co-localization of proteins of interest together with detailed myelin morphology. The lysolecithin model of de- and remyelination is shown as an example of a practical application of this technique, which can be routinely applied when high-resolution microscopy of central or peripheral myelinated tracts is required.

  3. Myelin regeneration in multiple sclerosis: targeting endogenous stem cells.

    PubMed

    Huang, Jeffrey K; Fancy, Stephen P J; Zhao, Chao; Rowitch, David H; Ffrench-Constant, Charles; Franklin, Robin J M

    2011-10-01

    Regeneration of myelin sheaths (remyelination) after central nervous system demyelination is important to restore saltatory conduction and to prevent axonal loss. In multiple sclerosis, the insufficiency of remyelination leads to the irreversible degeneration of axons and correlated clinical decline. Therefore, a regenerative strategy to encourage remyelination may protect axons and improve symptoms in multiple sclerosis. We highlight recent studies on factors that influence endogenous remyelination and potential promising pharmacological targets that may be considered for enhancing central nervous system remyelination.

  4. Central nervous system regeneration: from leech to opossum.

    PubMed

    Mladinic, M; Muller, K J; Nicholls, J G

    2009-06-15

    A major problem of neurobiology concerns the failure of injured mammalian spinal cord to repair itself. This review summarizes work done on two preparations in which regeneration can occur: the central nervous system of an invertebrate, the leech, and the spinal cord of an immature mammal, the opossum. The aim is to understand cellular and molecular mechanisms that promote and prevent regeneration. In the leech, an individual axon regrows successfully to re-establish connections with its synaptic target, while avoiding other neurons. Functions that were lost are thereby restored. Moreover, pairs of identified neurons become re-connected with appropriate synapses in culture. It has been shown that microglial cells and nitric oxide play key roles in leech CNS regeneration. In the opossum, the neonatal brain and spinal cord are so tiny that they survive well in culture. Fibres grow across spinal cord lesions in neonatal animals and in vitro, but axon regeneration stops abruptly between postnatal days 9 and 12. A comprehensive search has been made in spinal cords that can and cannot regenerate to identify genes and establish their locations. At 9 days, growth-promoting genes, their receptors and key transcription molecules are up-regulated. By contrast at 12 days, growth-inhibitory molecules associated with myelin are prominent. The complete sequence of the opossum genome and new methods for transfecting genes offer ways to determine which molecules promote and which inhibit spinal cord regeneration. These results lead to questions about how basic research on mechanisms of regeneration could be 'translated' into effective therapies for patients with spinal cord injuries. PMID:19525562

  5. Central nervous system regeneration: from leech to opossum.

    PubMed

    Mladinic, M; Muller, K J; Nicholls, J G

    2009-06-15

    A major problem of neurobiology concerns the failure of injured mammalian spinal cord to repair itself. This review summarizes work done on two preparations in which regeneration can occur: the central nervous system of an invertebrate, the leech, and the spinal cord of an immature mammal, the opossum. The aim is to understand cellular and molecular mechanisms that promote and prevent regeneration. In the leech, an individual axon regrows successfully to re-establish connections with its synaptic target, while avoiding other neurons. Functions that were lost are thereby restored. Moreover, pairs of identified neurons become re-connected with appropriate synapses in culture. It has been shown that microglial cells and nitric oxide play key roles in leech CNS regeneration. In the opossum, the neonatal brain and spinal cord are so tiny that they survive well in culture. Fibres grow across spinal cord lesions in neonatal animals and in vitro, but axon regeneration stops abruptly between postnatal days 9 and 12. A comprehensive search has been made in spinal cords that can and cannot regenerate to identify genes and establish their locations. At 9 days, growth-promoting genes, their receptors and key transcription molecules are up-regulated. By contrast at 12 days, growth-inhibitory molecules associated with myelin are prominent. The complete sequence of the opossum genome and new methods for transfecting genes offer ways to determine which molecules promote and which inhibit spinal cord regeneration. These results lead to questions about how basic research on mechanisms of regeneration could be 'translated' into effective therapies for patients with spinal cord injuries.

  6. Signals regulating myelination in peripheral nerves and the Schwann cell response to injury

    PubMed Central

    Glenn, Thomas D.; Talbot, William S.

    2013-01-01

    In peripheral nerves, Schwann cells form myelin, which facilitates the rapid conduction of action potentials along axons in the vertebrate nervous system. Myelinating Schwann cells are derived from neural crest progenitors in a step-wise process that is regulated by extracellular signals and transcription factors. In addition to forming the myelin sheath, Schwann cells orchestrate much of the regenerative response that occurs after injury to peripheral nerves. In response to injury, myelinating Schwann cells dedifferentiate into repair cells that are essential for axonal regeneration, and then redifferentiate into myelinating Schwann cells to restore nerve function. Although this remarkable plasticity has long been recognized, many questions remain unanswered regarding the signaling pathways regulating both myelination and the Schwann cell response to injury. PMID:23896313

  7. Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain.

    PubMed

    Gibson, Erin M; Purger, David; Mount, Christopher W; Goldstein, Andrea K; Lin, Grant L; Wood, Lauren S; Inema, Ingrid; Miller, Sarah E; Bieri, Gregor; Zuchero, J Bradley; Barres, Ben A; Woo, Pamelyn J; Vogel, Hannes; Monje, Michelle

    2014-05-01

    Myelination of the central nervous system requires the generation of functionally mature oligodendrocytes from oligodendrocyte precursor cells (OPCs). Electrically active neurons may influence OPC function and selectively instruct myelination of an active neural circuit. In this work, we use optogenetic stimulation of the premotor cortex in awake, behaving mice to demonstrate that neuronal activity elicits a mitogenic response of neural progenitor cells and OPCs, promotes oligodendrogenesis, and increases myelination within the deep layers of the premotor cortex and subcortical white matter. We further show that this neuronal activity-regulated oligodendrogenesis and myelination is associated with improved motor function of the corresponding limb. Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement.

  8. A zinc finger protein that regulates oligodendrocyte specification, migration and myelination in zebrafish.

    PubMed

    Sidik, Harwin; Talbot, William S

    2015-12-01

    Precise control of oligodendrocyte migration and development is crucial for myelination of axons in the central nervous system (CNS), but important questions remain unanswered about the mechanisms controlling these processes. In a zebrafish screen for myelination mutants, we identified a mutation in zinc finger protein 16-like (znf16l). znf16l mutant larvae have reduced myelin basic protein (mbp) expression and reduced CNS myelin. Marker, time-lapse and ultrastructural studies indicated that oligodendrocyte specification, migration and myelination are disrupted in znf16l mutants. Transgenic studies indicated that znf16l acts autonomously in oligodendrocytes. Expression of Zfp488 from mouse rescued mbp expression in znf16l mutants, indicating that these homologs have overlapping functions. Our results defined the function of a new zinc finger protein with specific function in oligodendrocyte specification, migration and myelination in the developing CNS.

  9. Roles of kinins in the nervous system.

    PubMed

    Negraes, Priscilla D; Trujillo, Cleber A; Pillat, Micheli M; Teng, Yang D; Ulrich, Henning

    2015-01-01

    The kallikrein-kinin system (KKS) is an endogenous pathway involved in many biological processes. Although primarily related to blood pressure control and inflammation, its activation goes beyond these effects. Neurogenesis and neuroprotection might be stimulated by bradykinin being of great interest for clinical applications following brain injury. This peptide is also an important player in spinal cord injury pathophysiology and recovery, in which bradykinin receptor blockers represent substantial therapeutic potential. Here, we highlight the participation of kinin receptors and especially bradykinin in mediating ischemia pathophysiology in the central and peripheral nervous systems. Moreover, we explore the recent advances on mechanistic and therapeutic targets for biological, pathological, and neural repair processes involving kinins. PMID:25839228

  10. Exercise and the autonomic nervous system.

    PubMed

    Fu, Qi; Levine, Benjamin D

    2013-01-01

    The autonomic nervous system plays a crucial role in the cardiovascular response to acute (dynamic) exercise in animals and humans. During exercise, oxygen uptake is a function of the triple-product of heart rate and stroke volume (i.e., cardiac output) and arterial-mixed venous oxygen difference (the Fick principle). The degree to which each of the variables can increase determines maximal oxygen uptake (V˙O2max). Both "central command" and "the exercise pressor reflex" are important in determining the cardiovascular response and the resetting of the arterial baroreflex during exercise to precisely match systemic oxygen delivery with metabolic demand. In general, patients with autonomic disorders have low levels of V˙O2max, indicating reduced physical fitness and exercise capacity. Moreover, the vast majority of the patients have blunted or abnormal cardiovascular response to exercise, especially during maximal exercise. There is now convincing evidence that some of the protective and therapeutic effects of chronic exercise training are related to the impact on the autonomic nervous system. Additionally, training induced improvement in vascular function, blood volume expansion, cardiac remodeling, insulin resistance and renal-adrenal function may also contribute to the protection and treatment of cardiovascular, metabolic and autonomic disorders. Exercise training also improves mental health, helps to prevent depression, and promotes or maintains positive self-esteem. Moderate-intensity exercise at least 30 minutes per day and at least 5 days per week is recommended for the vast majority of people. Supervised exercise training is preferable to maximize function capacity, and may be particularly important for patients with autonomic disorders. PMID:24095123

  11. VIIP: Central Nervous System (CNS) Modeling

    NASA Technical Reports Server (NTRS)

    Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry

    2015-01-01

    Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.

  12. Advances in Primary Central Nervous System Lymphoma.

    PubMed

    Patrick, Lauren B; Mohile, Nimish A

    2015-12-01

    Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors, definitive diagnosis requires brain biopsy, vitreoretinal biopsy, or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy. Long-term survival, however, is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first-line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment, with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging, requiring collaborative efforts between institutions. This review highlights recent advances in the biology, detection, and treatment of PCNSL in immunocompetent patients.

  13. [Histopathology of central nervous system cavernomas].

    PubMed

    Mosnier, J-F; Brunon, J; Nuti, C

    2007-06-01

    Central nervous system cavernomas are vascular malformations, which occur in two circumstances: sporadic forms and familial autosomal dominant forms. The lesion consists of enlarged, closely packed vessels without interposition of brain parenchyma, surrounded by hemosiderin and gliosis, calcified in few cases. In 80% of sporadic forms the lesion is unique, multiple lesions are rare (median: 4). In familial forms the lesions are always multiple. Cavernomas are often associated with other vascular malformations, especially with venous developmental anomalies. The size of cavernomas is variable from 1 mm to several centimeters. About 70% of cases are supratentorial and 30% in the posterior fossa, particularly in the brain stem. Macroscopic and histopathological findings are typical and the diagnostic is generally easy. PMID:17498756

  14. Scaffolds for central nervous system tissue engineering

    NASA Astrophysics Data System (ADS)

    He, Jin; Wang, Xiu-Mei; Spector, Myron; Cui, Fu-Zhai

    2012-03-01

    Traumatic injuries to the brain and spinal cord of the central nervous system (CNS) lead to severe and permanent neurological deficits and to date there is no universally accepted treatment. Owing to the profound impact, extensive studies have been carried out aiming at reducing inflammatory responses and overcoming the inhibitory environment in the CNS after injury so as to enhance regeneration. Artificial scaffolds may provide a suitable environment for axonal regeneration and functional recovery, and are of particular importance in cases in which the injury has resulted in a cavitary defect. In this review we discuss development of scaffolds for CNS tissue engineering, focusing on mechanism of CNS injuries, various biomaterials that have been used in studies, and current strategies for designing and fabricating scaffolds.

  15. Varicella Zoster Virus in the Nervous System

    PubMed Central

    Gilden, Don; Nagel, Maria; Cohrs, Randall; Mahalingam, Ravi; Baird, Nicholas

    2015-01-01

    Varicella zoster virus (VZV) is a ubiquitous, exclusively human alphaherpesvirus. Primary infection usually results in varicella (chickenpox), after which VZV becomes latent in ganglionic neurons along the entire neuraxis. As VZV-specific cell-mediated immunity declines in elderly and immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), frequently complicated by postherpetic neuralgia. VZV reactivation also produces multiple serious neurological and ocular diseases, such as cranial nerve palsies, meningoencephalitis, myelopathy, and VZV vasculopathy, including giant cell arteritis, with or without associated rash. Herein, we review the clinical, laboratory, imaging, and pathological features of neurological complications of VZV reactivation as well as diagnostic tests to verify VZV infection of the nervous system. Updates on the physical state of VZV DNA and viral gene expression in latently infected ganglia, neuronal, and primate models to study varicella pathogenesis and immunity are presented along with innovations in the immunization of elderly individuals to prevent VZV reactivation. PMID:26918131

  16. Nocardiosis of the Central Nervous System

    PubMed Central

    Anagnostou, Theodora; Arvanitis, Marios; Kourkoumpetis, Themistoklis K.; Desalermos, Athanasios; Carneiro, Herman A.

    2014-01-01

    Abstract Central nervous system (CNS) nocardiosis is a rare disease entity caused by the filamentous bacteria Nocardia species. We present a case series of 5 patients from our hospital and a review of the cases of CNS nocardiosis reported in the literature from January 2000 to December 2011. Our results indicate that CNS nocardiosis can occur in both immunocompromised and immunocompetent individuals and can be the result of prior pulmonary infection or can exist on its own. The most common predisposing factors are corticosteroid use (54% of patients) and organ transplantation (25%). Presentation of the disease is widely variable, and available diagnostic tests are far from perfect, often leading to delayed detection and initiation of treatment. The optimal therapeutic approach is still undetermined and depends on speciation, but lower mortality and relapse rates have been reported with a combination of targeted antimicrobial treatment including trimethoprim/sulfomethoxazole (TMP-SMX) for more than 6 months and neurosurgical intervention. PMID:24378740

  17. Varicella Zoster Virus in the Nervous System.

    PubMed

    Gilden, Don; Nagel, Maria; Cohrs, Randall; Mahalingam, Ravi; Baird, Nicholas

    2015-01-01

    Varicella zoster virus (VZV) is a ubiquitous, exclusively human alphaherpesvirus. Primary infection usually results in varicella (chickenpox), after which VZV becomes latent in ganglionic neurons along the entire neuraxis. As VZV-specific cell-mediated immunity declines in elderly and immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), frequently complicated by postherpetic neuralgia. VZV reactivation also produces multiple serious neurological and ocular diseases, such as cranial nerve palsies, meningoencephalitis, myelopathy, and VZV vasculopathy, including giant cell arteritis, with or without associated rash. Herein, we review the clinical, laboratory, imaging, and pathological features of neurological complications of VZV reactivation as well as diagnostic tests to verify VZV infection of the nervous system. Updates on the physical state of VZV DNA and viral gene expression in latently infected ganglia, neuronal, and primate models to study varicella pathogenesis and immunity are presented along with innovations in the immunization of elderly individuals to prevent VZV reactivation. PMID:26918131

  18. Advances in Primary Central Nervous System Lymphoma.

    PubMed

    Patrick, Lauren B; Mohile, Nimish A

    2015-12-01

    Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors, definitive diagnosis requires brain biopsy, vitreoretinal biopsy, or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy. Long-term survival, however, is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first-line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment, with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging, requiring collaborative efforts between institutions. This review highlights recent advances in the biology, detection, and treatment of PCNSL in immunocompetent patients. PMID:26475775

  19. PET imaging of the autonomic nervous system.

    PubMed

    Thackeray, James T; Bengel, Frank M

    2016-12-01

    The autonomic nervous system is the primary extrinsic control of heart rate and contractility, and is subject to adaptive and maladaptive changes in cardiovascular disease. Consequently, noninvasive assessment of neuronal activity and function is an attractive target for molecular imaging. A myriad of targeted radiotracers have been developed over the last 25 years for imaging various components of the sympathetic and parasympathetic signal cascades. While routine clinical use remains somewhat limited, a number of larger scale studies in recent years have supplied momentum to molecular imaging of autonomic signaling. Specifically, the findings of the ADMIRE HF trial directly led to United States Food and Drug Administration approval of 123I-metaiodobenzylguanidine (MIBG) for Single Photon Emission Computed Tomography (SPECT) assessment of sympathetic neuronal innervation, and comparable results have been reported using the analogous PET agent 11C-meta-hydroxyephedrine (HED). Due to the inherent capacity for dynamic quantification and higher spatial resolution, regional analysis may be better served by PET. In addition, preliminary clinical and extensive preclinical experience has provided a broad foundation of cardiovascular applications for PET imaging of the autonomic nervous system. Recent years have witnessed the growth of novel quantification techniques, expansion of multiple tracer studies, and improved understanding of the uptake of different radiotracers, such that the transitional biology of dysfunctional subcellular catecholamine handling can be distinguished from complete denervation. As a result, sympathetic neuronal molecular imaging is poised to play a role in individualized patient care, by stratifying cardiovascular risk, visualizing underlying biology, and guiding and monitoring therapy. PMID:27611712

  20. Neutron scattering from myelin revisited: bilayer asymmetry and water-exchange kinetics

    PubMed Central

    Denninger, Andrew R.; Demé, Bruno; Cristiglio, Viviana; LeDuc, Géraldine; Feller, W. Bruce; Kirschner, Daniel A.

    2014-01-01

    Rapid nerve conduction in the central and peripheral nervous systems (CNS and PNS, respectively) of higher vertebrates is brought about by the ensheathment of axons with myelin, a lipid-rich, multilamellar assembly of membranes. The ability of myelin to electrically insulate depends on the regular stacking of these plasma membranes and on the presence of a number of specialized membrane-protein assemblies in the sheath, including the radial component, Schmidt–Lanterman incisures and the axo–glial junctions of the paranodal loops. The disruption of this fine-structure is the basis for many demyelinating neuropathies in the CNS and PNS. Understanding the processes that govern myelin biogenesis, maintenance and destabilization requires knowledge of myelin structure; however, the tight packing of internodal myelin and the complexity of its junctional specializations make myelin a challenging target for comprehensive structural analysis. This paper describes an examination of myelin from the CNS and PNS using neutron diffraction. This investigation revealed the dimensions of the bilayers and aqueous spaces of myelin, asymmetry between the cytoplasmic and extracellular leaflets of the membrane, and the distribution of water and exchangeable hydrogen in internodal multilamellar myelin. It also uncovered differences between CNS and PNS myelin in their water-exchange kinetics. PMID:25478838

  1. TACE (ADAM17) inhibits Schwann cell myelination.

    PubMed

    La Marca, Rosa; Cerri, Federica; Horiuchi, Keisuke; Bachi, Angela; Feltri, M Laura; Wrabetz, Lawrence; Blobel, Carl P; Quattrini, Angelo; Salzer, James L; Taveggia, Carla

    2011-06-12

    Tumor necrosis factor-α-converting enzyme (TACE; also known as ADAM17) is a proteolytic sheddase that is responsible for the cleavage of several membrane-bound molecules. We report that TACE cleaves neuregulin-1 (NRG1) type III in the epidermal growth factor domain, probably inactivating it (as assessed by deficient activation of the phosphatidylinositol-3-OH kinase pathway), and thereby negatively regulating peripheral nervous system (PNS) myelination. Lentivirus-mediated knockdown of TACE in vitro in dorsal root ganglia neurons accelerates the onset of myelination and results in hypermyelination. In agreement, motor neurons of conditional knockout mice lacking TACE specifically in these cells are significantly hypermyelinated, and small-caliber fibers are aberrantly myelinated. Further, reduced TACE activity rescues hypomyelination in NRG1 type III haploinsufficient mice in vivo. We also show that the inhibitory effect of TACE is neuron-autonomous, as Schwann cells lacking TACE elaborate myelin of normal thickness. Thus, TACE is a modulator of NRG1 type III activity and is a negative regulator of myelination in the PNS.

  2. Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy

    NASA Astrophysics Data System (ADS)

    Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Claude Boccara, A.; Bourdieu, Laurent

    2011-11-01

    Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

  3. Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy.

    PubMed

    Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Boccara, A Claude; Bourdieu, Laurent

    2011-11-01

    Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

  4. Central nervous system manifestations of neonatal lupus: a systematic review.

    PubMed

    Chen, C C; Lin, K-L; Chen, C-L; Wong, A May-Kuen; Huang, J-L

    2013-12-01

    Neonatal lupus is a rare and acquired autoimmune disease. Central nervous system abnormalities are potential manifestations in neonatal lupus. Through a systematic literature review, we analyzed the clinical features of previously reported neonatal lupus cases where central nervous system abnormalities had been identified. Most reported neonatal lupus patients with central nervous system involvement were neuroimaging-determined and asymptomatic. Only seven neonatal lupus cases were identified as having a symptomatic central nervous system abnormality which caused physical disability or required neurosurgery. A high percentage of these neurosymptomatic neonatal lupus patients had experienced a transient cutaneous skin rash and had no maternal history of autoimmune disease before pregnancy.

  5. Molecular disruptions of the panglial syncytium block potassium siphoning and axonal saltatory conduction: pertinence to neuromyelitis optica and other demyelinating diseases of the central nervous system.

    PubMed

    Rash, J E

    2010-07-28

    The panglial syncytium maintains ionic conditions required for normal neuronal electrical activity in the central nervous system (CNS). Vital among these homeostatic functions is "potassium siphoning," a process originally proposed to explain astrocytic sequestration and long-distance disposal of K(+) released from unmyelinated axons during each action potential. Fundamentally different, more efficient processes are required in myelinated axons, where axonal K(+) efflux occurs exclusively beneath and enclosed within the myelin sheath, precluding direct sequestration of K(+) by nearby astrocytes. Molecular mechanisms for entry of excess K(+) and obligatorily-associated osmotic water from axons into innermost myelin are not well characterized, whereas at the output end, axonally-derived K(+) and associated osmotic water are known to be expelled by Kir4.1 and aquaporin-4 channels concentrated in astrocyte endfeet that surround capillaries and that form the glia limitans. Between myelin (input end) and astrocyte endfeet (output end) is a vast network of astrocyte "intermediaries" that are strongly inter-linked, including with myelin, by abundant gap junctions that disperse excess K(+) and water throughout the panglial syncytium, thereby greatly reducing K(+)-induced osmotic swelling of myelin. Here, I review original reports that established the concept of potassium siphoning in unmyelinated CNS axons, summarize recent revolutions in our understanding of K(+) efflux during axonal saltatory conduction, then describe additional components required by myelinated axons for a newly-described process of voltage-augmented "dynamic" potassium siphoning. If any of several molecular components of the panglial syncytium are compromised, K(+) siphoning is blocked, myelin is destroyed, and axonal saltatory conduction ceases. Thus, a common thread linking several CNS demyelinating diseases is the disruption of potassium siphoning/water transport within the panglial syncytium

  6. Molecular Disruptions of the Panglial Syncytium Block Potassium Siphoning and Axonal Saltatory Conduction: Pertinence to Neuromyelitis Optica and other Demyelinating Diseases of the Central Nervous System

    PubMed Central

    Rash, John E.

    2009-01-01

    The panglial syncytium maintains ionic conditions required for normal neuronal electrical activity in the central nervous system (CNS). Vital among these homeostatic functions is “potassium siphoning”, a process originally proposed to explain astrocytic sequestration and long-distance disposal of K+ released from unmyelinated axons during each action potential. Fundamentally different, more efficient processes are required in myelinated axons, where axonal K+ efflux occurs exclusively beneath and enclosed within the myelin sheath, precluding direct sequestration of K+ by nearby astrocytes. Molecular mechanisms for entry of excess K+ and obligatorily-associated osmotic water from axons into innermost myelin are not well characterized, whereas at the output end, axonally-derived K+ and associated osmotic water are known to be expelled by Kir4.1 and aquaporin-4 channels concentrated in astrocyte endfeet that surround capillaries and that form the glia limitans. Between myelin (input end) and astrocyte endfeet (output end) is a vast network of astrocyte “intermediaries” that are strongly inter-linked, including with myelin, by abundant gap junctions that disperse excess K+ and water throughout the panglial syncytium, thereby greatly reducing K+-induced osmotic swelling of myelin. Here, I review original reports that established the concept of potassium siphoning in unmyelinated CNS axons, summarize recent revolutions in our understanding of K+ efflux during axonal saltatory conduction, then describe additional components required by myelinated axons for a newly-described process of voltage-augmented “dynamic” potassium siphoning. If any of several molecular components of the panglial syncytium are compromised, K+ siphoning is blocked, myelin is destroyed, and axonal saltatory conduction ceases. Thus, a common thread linking several CNS demyelinating diseases is the disruption of potassium siphoning/water transport within the panglial syncytium. Continued

  7. A Model of Tight Junction Function In CNS Myelinated Axons

    PubMed Central

    Gow, Alexander; Devaux, Jerome

    2010-01-01

    The insulative properties of myelin sheaths in the central and peripheral nervous systems (CNS and PNS) are widely thought to derive from the high resistance and low capacitance of the constituent membranes. Although this view adequately accounts for myelin function in large diameter PNS fibers, it poorly reflects the behavior of small fibers that are prominent in many regions of the CNS. Herein, we develop a computational model to more accurately represent conduction in small fibers. By incorporating structural features that, hitherto, have not been simulated, we demonstrate that myelin tight junctions improve saltatory conduction by reducing current flow through the myelin, limiting axonal membrane depolarization and restraining the activation of ion channels beneath the myelin sheath. Accordingly, our simulations provide a novel view of myelin by which tight junctions minimize charging of the membrane capacitance and lower the membrane time constant to improve the speed and accuracy of transmission in small diameter fibers. This study establishes possible mechanisms whereby TJs affect conduction in the absence of overt perturbations to myelin architecture and may in part explain the tremor and gait abnormalities observed in Claudin 11-null mice. PMID:20102674

  8. Cdon, a cell surface protein, mediates oligodendrocyte differentiation and myelination.

    PubMed

    Wang, Li-Chun; Almazan, Guillermina

    2016-06-01

    During central nervous system development, oligodendrocyte progenitors (OLPs) establish multiple branched processes and axonal contacts to initiate myelination. A complete understanding of the molecular signals implicated in cell surface interaction to initiate myelination/remyelination is currently lacking. The objective of our study was to assess whether Cdon, a cell surface protein that was shown to participate in muscle and neuron cell development, is involved in oligodendrocyte (OLG) differentiation and myelination. Here, we demonstrate that endogenous Cdon protein is expressed in OLPs, increasing in the early differentiation stages and decreasing in mature OLGs. Immunocytochemistry of endogenous Cdon showed localization on both OLG cell membranes and cellular processes exhibiting puncta- or varicosity-like structures. Cdon knockdown with siRNA decreased protein levels by 62% as well as two myelin-specific proteins, MBP and MAG. Conversely, overexpression of full-length rat Cdon increased myelin proteins in OLGs. The complexity of OLGs branching and contact point numbers with axons were also increased in Cdon overexpressing cells growing alone or in coculture with dorsal root ganglion neurons (DRGNs). Furthermore, myelination of DRGNs was decreased when OLPs were transfected with Cdon siRNA. Altogether, our results suggest that Cdon participates in OLG differentiation and myelination, most likely in the initial stages of development.

  9. Alterations in hippocampal myelin and oligodendrocyte precursor cells during epileptogenesis.

    PubMed

    Luo, Yuanyuan; Hu, Qiao; Zhang, Qian; Hong, Siqi; Tang, Xiaoju; Cheng, Li; Jiang, Li

    2015-11-19

    Recent reports have described damage to myelinated fibers in the central nervous system (CNS) in patients with temporal lobe epilepsy (TLE) and animal models. However, only limited data are available on the dynamic changes that occur in myelinated fibers, oligodendrocytes (which are myelin-forming cells), and oligodendrocyte precursor cells (OPCs), which are a reservoir of new oligodendrocytes, in the hippocampus throughout epileptogenesis. The current study was designed to examine this issue using a rat model of lithium-pilocarpine-induced epilepsy. Electroencephalography (EEG), immunofluorescence, and Western blot analysis showed that the loss of myelin and oligodendrocytes in the rat hippocampus began during the acute stage of epileptogenesis, and the severity of this loss increased throughout epileptogenesis. Accompanying this loss of myelin and oligodendrocytes, OPCs in the rat hippocampus became activated and their populations increased during several phases of epileptogenesis (the acute, latent and chronic phases). The transcription factors olig1 and olig2, which play crucial roles in regulating OPC proliferation, differentiation and remyelination, were up-regulated during the early phases (the acute and latent phases) followed by a sharp decline in their expression during the chronic and late chronic phases. This study is the first to confirm the loss of myelin and oligodendrocytes during lithium-pilocarpine-induced epileptogenesis accompanied by a transient increase in the number of OPCs. Prevention of the loss of myelin and oligodendrocytes may provide a novel treatment strategy for epilepsy.

  10. Parasitoses with central nervous system involvement.

    PubMed

    Finsterer, Josef; Frank, Marlies

    2014-10-01

    Most of the parasitoses manifest systemically, including the central nervous system (CNS). Among the most prevalent parasitoses in Central Europe (cysticercosis, toxocarosis, echinococcosis, and toxoplasmosis), cerebral involvement is well recognized and part of the clinical presentation, which cannot be neglected. CNS involvement results from invasion of larvae of these parasites via the blood stream or by direct migration into the CNS. Most frequently larvae reside within the cerebral parenchyma, but sometimes also within the ventricles, in the meningeas within cerebral aneurysms, or in the parenchyma of the spinal cord. Depending on the stage of their development, they cause a local defect or more widespread damage, such as encephalitis, ventriculitis, ependymitis, arachnoiditis, meningitis, myelitis, polyradiculitis, mechanical obstruction of the arterial or cerebrospinal fluid (CSF) flow, or vasculitis with appropriate clinical presentations. These include epilepsy, headache, impaired consciousness, orientation, cognition, focal neurological motor, sensory, or vegetative deficits, or visual impairment. CNS involvement is diagnosed on the clinical presentation, the epidemiological background, blood and CSF investigations, imaging studies, and sometimes biopsy. Treatment is based on various antihelminthic agents and, occasionally, surgery. PMID:25297698

  11. Localized hyperthermia in the central nervous system

    SciTech Connect

    Lyons, B.E. Jr.

    1986-01-01

    A new localized treatment modality for malignant brain tumors is hyperthermia. Primary brain tumors are ideally suited to localized therapies because they are initially found in a single area of the brain and local recurrence is the general rule, despite aggressive multimodality treatment. The potential of hyperthermia is based on the rationale that these tumors contain a heterogeneous anaplastic cell population. In contrast to radiation and chemotherapy, hyperthermia is equally effective against both hypoxic and oxygenated cells. Moreover, higher temperatures result in tissues that have an inability to cool themselves through perfusion. The feasibility of localized heating in normal and malignant brain tissue was investigated using external ultrasound and microwave applicators and an interstitial microwave antenna array. The ability to generate uniform temperature distributions using these systems was tested in thermal dosimetry studies. Lesion threshold studies were performed to define the acute and chronic histopathological effects of localized hyperthermia in normal brain tissue. Results demonstrated that these techniques can effectively heat clinically relevant volumes of brain tissue to therapeutic temperatures in an extremely controlled and precise manner. Thresholds for cytological damage have been defined over a range of time/temperature parameters. Various physical and physiological factors within the central nervous system as they relate to temperature exposure have also been defined. These feasibility and toxicity studies have led to the initiation of Phase I clinical trials of hyperthermia in combination with radiation therapy at several institutions.

  12. Pathogenesis of central nervous system tuberculosis.

    PubMed

    Be, Nicholas A; Kim, Kwang Sik; Bishai, William R; Jain, Sanjay K

    2009-03-01

    Central Nervous System (CNS) tuberculosis is a serious, often fatal form of tuberculosis, predominantly affecting young children. HIV co-infection and drug resistant strains of Mycobacterium tuberculosis are making the diagnosis and treatment of CNS tuberculosis more complicated. Current concepts about the pathogenesis of CNS tuberculosis are based on necropsy studies done in 1933, which suggest that tuberculous meningitis develops subsequent to the rupture into the cerebrospinal fluid of tuberculomas that form around M. tuberculosis deposited in the brain parenchyma and meninges during the initial hematogenous dissemination. Foreign antigens including pathogens deposited in the brain parenchyma are not detected efficiently by the immune system in the CNS. These experimental data may explain the clinical observation of delayed "paradoxical" enlargement or development of intracranial tuberculomas, observed several weeks to months in patients receiving anti-tuberculous therapy. Since severe sequelae are observed even when CNS tuberculosis is treated effectively, it is important to develop preventive strategies for this disease. Recent data utilizing animal models suggests that, in addition to host factors, M. tuberculosis genes and their encoded proteins may contribute specifically to bacterial invasion and survival in the CNS. Understanding how these microbial factors affect CNS disease would be essential to developing such preventive strategies.

  13. [Diagnostic imaging of central nervous system vasculitis].

    PubMed

    Yokota, Hajime; Yamada, Kei

    2015-03-01

    Vasculitis involving the central nervous system presents with infarction and hemorrhage, which are often nonspecific findings. Laboratory examinations are essential for diagnosis of vasculitis in addition to comprehensive and systematic review of the clinical course. Although most findings tend to be nonspecific, enhancement and thickening of the vascular wall indicate vasculitis. Visualization of the vascular wall requires selection of the appropriate imaging modality and mode of image acquisition. Contrast-enhanced CT, MRI, and FDG-PET are useful for visualizing large vessel vasculitis, while CT, MRI, and angiography are effective for medium vessel vasculitis. The use of ultrasound is limited to evaluating vessels on the body surface. Although relatively thick vessels can be demonstrated by angiography, complete survey of small vessels is difficult. Here, we summarize the characteristics of each imaging modality and imaging findings of typical vasculitides-Takayasu arteritis, giant cell arteritis, ANCA-associated vasculitis, Behçet's disease, primary angiitis of the CNS, and vasculitis associated with systemic disease. Differential diagnoses are also shown, including infective endocarditis, tuberculous meningitis, Ehlers-Danlos syndrome, and reversible cerebral vasoconstriction syndrome. PMID:25846439

  14. Schwann cell remyelination and recurrent demyelination in the central nervous system of mice infected with attenuated Theiler's virus.

    PubMed

    Dal Canto, M C; Lipton, H L

    1980-01-01

    Theiler's murine encephalomyelitis virus (TMEV) infection produces a chronic demyelinating disease in mice, and myelin breakdown appears to be immune-mediated. By using an attenuated TMEC strain, WW virus, to infect mice, the course of the disease was slowed and the severity of the inflammatory and glial responses were reduced. In this circumstance, most of the demyelinating lesions showed extensive remyelination, predominantly by Schwann cells. In addition, it was demonstrated that there was recurrent demyelinating activity in the central nervous system (CNS) of infected animals. It is suggested that the rapidity and intensity of demyelinating lesions may influence the potential for remyelination and that Schwann cell participation may be a more important mechanism of myelin repair than it is now thought to be. The fact that there is a recurrent demyelination in TMEV infection increases its relevance as an experimental animal model for multiple sclerosis.

  15. Ex vivo and in vivo coherent Raman imaging of the peripheral and central nervous system

    NASA Astrophysics Data System (ADS)

    Huff, Terry Brandon

    A hallmark of nervous system disorders is damage or degradation of the myelin sheath. Unraveling the mechanisms underlying myelin degeneration and repair represent one of the great challenges in medicine. This thesis work details the development and utilization of advanced optical imaging methods to gain insight into the structure and function of myelin in both healthy and diseased states in the in vivo environment. This first part of this thesis discusses ex vivo studies of the effects of high-frequency stimulation of spinal tissues on the structure of the node of Ranvier as investigated by coherent anti-Stokes Raman scattering (CARS) imaging (manuscript submitted to Journal of Neurosciece). Reversible paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation, beginning minutes after the onset and continuing for up to 10 min after stimulation was ceased. A mechanistic study revealed a Ca2+ dependent pathway: high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down. Also, the construction of dual-scanning CARS microscope for large area mapping of CNS tissues is detailed (Optics Express, 2008, 16:19396-193409). A confocal scanning head equipped with a rotating polygon mirror provides high speed, high resolution imaging and is coupled with a motorized sample stage to generate high-resolution large-area images of mouse brain coronal section and guinea pig spinal cord cross section. The polygon mirror decreases the mosaic acquisition time significantly without reducing the resolution of individual images. The ex vivo studies are then extended to in vivo imaging of mouse sciatic nerve tissue by CARS and second harmonic generation (SHG) imaging (Journal of Microscopy, 2007, 225: 175-182). Following a minimally invasive surgery to open the skin, CARS imaging of myelinated axons and SHG imaging of the

  16. Is central nervous system an immune-privileged site?

    PubMed

    Shrestha, R; Millington, O; Brewer, J; Bushell, T

    2013-01-01

    The central nervous system (CNS) was once considered to be an immune-privileged area. However, increasing evidence shows that the central nervous system is not an immune-privileged but is an active surveillance site. There is a bi-directional communication between the central nervous system and immune system. Normally, immune cells migrate into the central nervous system microenvironment through choroid plexus and interact with the central nervous system resident cells through either through neuromediators or immunomediators. This finding has led to a significant interest in neuroimmunological interactions and investigation onto the role of the immune system in the pathology of various neurological disorders and examine whether it can be targeted to produce novel therapeutic strategies. PMID:23774427

  17. Gap junctions in the nervous system.

    PubMed

    Rozental, R; Giaume, C; Spray, D C

    2000-04-01

    Synapses are classically defined as close connections between two nerve cells or between a neuronal cell and a muscle or gland cell across which a chemical signal (i.e., a neurotransmitter) and/or an electrical signal (i.e., current-carrying ions) can pass. The definition of synapse was developed by Charles Sherrington and by Ramon y Cajal at the beginning of this century and refined by John Eccles and Bernard Katz 50 years later; in this collection of papers, the definition of synapses is discussed further in the chapter by Mike Bennett. who provided the first functional demonstration of electrical transmission via gap junction channels between vertebrate neurons. As is evidenced by the range of topics covered in this issue, research dealing with gap junctions in the nervous system has expanded enormously in the past decade, major findings being that specific cell types in the brain expresses specific types of connexins and that expression patterns coincide with tissue compartmentalization and function and that these compartments change during development.

  18. Hemoglobin potentiates central nervous system damage.

    PubMed Central

    Sadrzadeh, S M; Anderson, D K; Panter, S S; Hallaway, P E; Eaton, J W

    1987-01-01

    Iron and iron compounds--including mammalian hemoglobins--catalyze hydroxyl radical production and lipid peroxidation. To determine whether hemoglobin-mediated lipid peroxidation might be important in hemorrhagic injuries to the central nervous system (CNS), we studied the effects of purified hemoglobin on CNS homogenates and injected hemoglobin into the spinal cords of anesthetized cats. Hemoglobin markedly inhibits Na/K ATPase activity in CNS homogenates and spinal cords of living cats. Hemoglobin also catalyzes substantial peroxidation of CNS lipids. Importantly, the potent iron chelator, desferrioxamine, blocks these adverse effects of hemoglobin, both in vitro and in vivo. Because desferrioxamine is not known to interact with heme iron, these results indicate that free iron, derived from hemoglobin, is the proximate toxic species. Overall, our data suggest that hemoglobin, released from red cells after trauma, can promote tissue injury through iron-dependent mechanisms. Suppression of this damage by desferrioxamine suggests a rational therapeutic approach to management of trauma-induced CNS injury. Images PMID:3027133

  19. Time Perception Mechanisms at Central Nervous System

    PubMed Central

    Fontes, Rhailana; Ribeiro, Jéssica; Gupta, Daya S.; Machado, Dionis; Lopes-Júnior, Fernando; Magalhães, Francisco; Bastos, Victor Hugo; Rocha, Kaline; Marinho, Victor; Lima, Gildário; Velasques, Bruna; Ribeiro, Pedro; Orsini, Marco; Pessoa, Bruno; Leite, Marco Antonio Araujo; Teixeira, Silmar

    2016-01-01

    The five senses have specific ways to receive environmental information and lead to central nervous system. The perception of time is the sum of stimuli associated with cognitive processes and environmental changes. Thus, the perception of time requires a complex neural mechanism and may be changed by emotional state, level of attention, memory and diseases. Despite this knowledge, the neural mechanisms of time perception are not yet fully understood. The objective is to relate the mechanisms involved the neurofunctional aspects, theories, executive functions and pathologies that contribute the understanding of temporal perception. Articles form 1980 to 2015 were searched by using the key themes: neuroanatomy, neurophysiology, theories, time cells, memory, schizophrenia, depression, attention-deficit hyperactivity disorder and Parkinson’s disease combined with the term perception of time. We evaluated 158 articles within the inclusion criteria for the purpose of the study. We conclude that research about the holdings of the frontal cortex, parietal, basal ganglia, cerebellum and hippocampus have provided advances in the understanding of the regions related to the perception of time. In neurological and psychiatric disorders, the understanding of time depends on the severity of the diseases and the type of tasks. PMID:27127597

  20. Central nervous system tumors in Mexican children.

    PubMed

    De la Torre Mondragón, L; Ridaura Sanz, C; Reyes Mujica, M; Rueda Franco, F

    1993-08-01

    Five hundred and seventy primary central nervous system (CNS) tumors from the Department of Pathology at the National Institute of Pediatrics in Mexico City, collected from 1970 to 1989, were histologically reclassified in order to find out their relative incidence as well as their outstanding features. With this, we could establish a frame of reference for our local population, contributing to the epidemiological analysis of these entities. All the tumors were examined independently by two pathologists (C.R. and M.R.), using the classification of Rorke et al. Histological type, patient age and sex, and tumor location were analyzed. CNS tumors were the secondmost frequently encountered solid tumors, after lymphomas, and were increasing in incidence at a rate of 2.2 annually. Children in the age group 0-9 years were most often affected, and there was a predominance of male patients. Astrocytoma and medulloblastoma were the most common tumor types. The infratentorial region was the most frequent tumor location in the 2- to 9-year age group. By contrast, in the under 2-year-olds a supratentorial location was more frequent, and the incidence of germ cell tumors was proportionally high. In general, some histological types seemed to be associated with particular age groups. Although we found primitive neuroectodermal tumors to be the fifth most common at all ages (except for medulloblastoma), many other authors do not report a similar finding.

  1. Environmental effects on the central nervous system.

    PubMed Central

    Paulson, G W

    1977-01-01

    The central nervous system (CNS) is designed to respond to the environment and is peculiarly vulnerable to many of the influences found in the environment. Utilizing an anatomical classification (cortex, cerebellum, peripheral nerves) major toxins and stresses are reviewed with selections from recent references. Selective vulnerability of certain areas to particular toxins is apparent at all levels of the CNS, although the amount of damage produced by any noxious agent depends on the age and genetic substrate of the subject. It is apparent that the effects of certain well known and long respected environmental toxins such as lead, mercury, etc., deserve continued surveillance. In addition, the overwhelming impact on the CNS of social damages such as trauma, alcohol, and tobacco cannot be ignored by environmentalists. The effect of the hospital and therapeutic environment has become apparent in view of increased awareness of iatrogenic disorders. The need for particular laboratory tests, for example, examination of CSF and nerve conduction toxicity studies, is suggested. Epidemics such as the recent solvent neuropathies suggest a need for continued animal studies that are chronic, as well as acute evaluations when predicting the potential toxic effects of industrial compounds. PMID:202447

  2. Epidemiology of central nervous system mycoses.

    PubMed

    Chakrabarti, Arunaloke

    2007-01-01

    Fungal infections of the central nervous system (CNS) were considered rare until the 1970s. This is no longer true in recent years due to widespread use of corticosteroids, cytotoxic drugs and antibiotics. Immunocompromised patients with underlying malignancy organ transplantations and acquired immune deficiency syndrome are all candidates for acquiring fungal infections either in meninges or brain. A considerable number of cases of CNS fungal infections even in immunocompetent hosts have been reported. A vast array of fungi may cause infection in the CNS, but barring a few, most of them are anecdotal case reports. Cryptococcus neoformans, Candida albicans, Coccidioides immitis. Histoplasma capsulatum are common causes of fungal meningitis; Aspergillus spp, Candida spp, Zygomycetes and some of the melanized fungi are known to cause mass lesions in brain. Few fungi like C. neoformans, Cladophialophora bantiana, Exophiala dermatitidis, Ramichloridium mackenzie, Ochroconis gallopava are considered as true neurotropic fungi. Most of the fungi causing CNS infection are saprobes with worldwide distribution; a few are geographically restricted like Coccidioides immitis. The infections reach the CNS either by the hematogenous route or by direct extension from colonized sinuses or ear canal or by direct inoculation during neurosurgical procedures. PMID:17921647

  3. Central Nervous System Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Boulware, David R.; Marais, Suzaan; Scriven, James; Wilkinson, Robert J.; Meintjes, Graeme

    2013-01-01

    Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) develops in 9 %–47 % of persons with HIV infection and a CNS opportunistic infection who start antiretroviral therapy and is associated with a mortality rate of 13 %–75 %. These rates vary according to the causative pathogen. Common CNS-IRIS events occur in relation to Cryptococcus, tuberculosis (TB), and JC virus, but several other mycobacteria, fungi, and viruses have been associated with IRIS. IRIS symptoms often mimic the original infection, and diagnosis necessitates consideration of treatment failure, microbial resistance, and an additional neurological infection. These diagnostic challenges often delay IRIS diagnosis and treatment. Corticosteroids have been used to treat CNS-IRIS, with variable responses; the best supportive evidence exists for the treatment of TB-IRIS. Pathogenic mechanisms vary: Cryptococcal IRIS is characterized by a paucity of cerebrospinal inflammation prior to antiretroviral therapy, whereas higher levels of inflammatory markers at baseline predispose to TB meningitis IRIS. This review focuses on advances in the understanding of CNS-IRIS over the past 2 years. PMID:24173584

  4. Plants and the central nervous system.

    PubMed

    Carlini, E A

    2003-06-01

    This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS). In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments. Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp. (Ma Huang), Paullinia spp. (guaraná), Catha edulis Forssk. (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized. Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill. and the mixture of Psychotria viridis Ruiz and Pav. and Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton. Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp. and Piper methysticum G. Forst.), were also analysed.Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed.

  5. Diabetes and the enteric nervous system.

    PubMed

    Chandrasekharan, B; Srinivasan, S

    2007-12-01

    Diabetes is associated with several changes in gastrointestinal (GI) motility and associated symptoms such as nausea, bloating, abdominal pain, diarrhoea and constipation. The pathogenesis of altered GI functions in diabetes is multifactorial and the role of the enteric nervous system (ENS) in this respect has gained significant importance. In this review, we summarize the research carried out on diabetes-related changes in the ENS. Changes in the inhibitory and excitatory enteric neurons are described highlighting the role of loss of inhibitory neurons in early diabetic enteric neuropathy. The functional consequences of these neuronal changes result in altered gastric emptying, diarrhoea or constipation. Diabetes can also affect GI motility through changes in intestinal smooth muscle or alterations in extrinsic neuronal control. Hyperglycaemia and oxidative stress play an important role in the pathophysiology of these ENS changes. Antioxidants to prevent or treat diabetic GI motility problems have therapeutic potential. Recent research on the nerve-immune interactions demonstrates inflammation-associated neurodegeneration which can lead to motility related problems in diabetes. PMID:17971027

  6. Early animal evolution and the origins of nervous systems.

    PubMed

    Budd, Graham E

    2015-12-19

    Understanding the evolution of early nervous systems is hazardous because we lack good criteria for determining homology between the systems of distant taxa; the timing of the evolutionary events is contested, and thus the relevant ecological and geological settings for them are also unclear. Here I argue that no simple approach will resolve the first issue, but that it remains likely that animals evolved relatively late, and that their nervous systems thus arose during the late Ediacaran, in a context provided by the changing planktonic and benthic environments of the time. The early trace fossil provides the most concrete evidence for early behavioural diversification, but it cannot simply be translated into increasing nervous system complexity: behavioural complexity does not map on a one-to-one basis onto nervous system complexity, both because of possible limitations to behaviour caused by the environment and because we know that even organisms without nervous systems are capable of relatively complex behaviour.

  7. Early animal evolution and the origins of nervous systems

    PubMed Central

    Budd, Graham E.

    2015-01-01

    Understanding the evolution of early nervous systems is hazardous because we lack good criteria for determining homology between the systems of distant taxa; the timing of the evolutionary events is contested, and thus the relevant ecological and geological settings for them are also unclear. Here I argue that no simple approach will resolve the first issue, but that it remains likely that animals evolved relatively late, and that their nervous systems thus arose during the late Ediacaran, in a context provided by the changing planktonic and benthic environments of the time. The early trace fossil provides the most concrete evidence for early behavioural diversification, but it cannot simply be translated into increasing nervous system complexity: behavioural complexity does not map on a one-to-one basis onto nervous system complexity, both because of possible limitations to behaviour caused by the environment and because we know that even organisms without nervous systems are capable of relatively complex behaviour. PMID:26554037

  8. Extraversion, Neuroticism and Strength of the Nervous System

    ERIC Educational Resources Information Center

    Frigon, Jean-Yves

    1976-01-01

    The hypothesized identity of the dimensions of extraversion-introversion and strength of the nervous system was tested on four groups of nine subjects (neurotic extraverts, stable extraverts, neurotic introverts, stable introverts). Strength of the subjects' nervous system was estimated using the electroencephalographic (EEG) variant of extinction…

  9. Influence of myelin proteins on the structure and dynamics of a model membrane with emphasis on the low temperature regime

    SciTech Connect

    Knoll, W.; Peters, J.; Kursula, P.; Gerelli, Y.; Natali, F.

    2014-11-28

    Myelin is an insulating, multi-lamellar membrane structure wrapped around selected nerve axons. Increasing the speed of nerve impulses, it is crucial for the proper functioning of the vertebrate nervous system. Human neurodegenerative diseases, such as multiple sclerosis, are linked to damage to the myelin sheath through demyelination. Myelin exhibits a well defined subset of myelin-specific proteins, whose influence on membrane dynamics, i.e., myelin flexibility and stability, has not yet been explored in detail. In a first paper [W. Knoll, J. Peters, P. Kursula, Y. Gerelli, J. Ollivier, B. Demé, M. Telling, E. Kemner, and F. Natali, Soft Matter 10, 519 (2014)] we were able to spotlight, through neutron scattering experiments, the role of peripheral nervous system myelin proteins on membrane stability at room temperature. In particular, the myelin basic protein and peripheral myelin protein 2 were found to synergistically influence the membrane structure while keeping almost unchanged the membrane mobility. Further insight is provided by this work, in which we particularly address the investigation of the membrane flexibility in the low temperature regime. We evidence a different behavior suggesting that the proton dynamics is reduced by the addition of the myelin basic protein accompanied by negligible membrane structural changes. Moreover, we address the importance of correct sample preparation and characterization for the success of the experiment and for the reliability of the obtained results.

  10. Influence of myelin proteins on the structure and dynamics of a model membrane with emphasis on the low temperature regime

    NASA Astrophysics Data System (ADS)

    Knoll, W.; Peters, J.; Kursula, P.; Gerelli, Y.; Natali, F.

    2014-11-01

    Myelin is an insulating, multi-lamellar membrane structure wrapped around selected nerve axons. Increasing the speed of nerve impulses, it is crucial for the proper functioning of the vertebrate nervous system. Human neurodegenerative diseases, such as multiple sclerosis, are linked to damage to the myelin sheath through demyelination. Myelin exhibits a well defined subset of myelin-specific proteins, whose influence on membrane dynamics, i.e., myelin flexibility and stability, has not yet been explored in detail. In a first paper [W. Knoll, J. Peters, P. Kursula, Y. Gerelli, J. Ollivier, B. Demé, M. Telling, E. Kemner, and F. Natali, Soft Matter 10, 519 (2014)] we were able to spotlight, through neutron scattering experiments, the role of peripheral nervous system myelin proteins on membrane stability at room temperature. In particular, the myelin basic protein and peripheral myelin protein 2 were found to synergistically influence the membrane structure while keeping almost unchanged the membrane mobility. Further insight is provided by this work, in which we particularly address the investigation of the membrane flexibility in the low temperature regime. We evidence a different behavior suggesting that the proton dynamics is reduced by the addition of the myelin basic protein accompanied by negligible membrane structural changes. Moreover, we address the importance of correct sample preparation and characterization for the success of the experiment and for the reliability of the obtained results.

  11. Production and use of lentivirus to selectively transduce primary oligodendrocyte precursor cells for in vitro myelination assays.

    PubMed

    Peckham, Haley M; Ferner, Anita H; Giuffrida, Lauren; Murray, Simon S; Xiao, Junhua

    2015-01-12

    Myelination is a complex process that involves both neurons and the myelin forming glial cells, oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). We use an in vitro myelination assay, an established model for studying CNS myelination in vitro. To do this, oligodendrocyte precursor cells (OPCs) are added to the purified primary rodent dorsal root ganglion (DRG) neurons to form myelinating co-cultures. In order to specifically interrogate the roles that particular proteins expressed by oligodendrocytes exert upon myelination we have developed protocols that selectively transduce OPCs using the lentivirus overexpressing wild type, constitutively active or dominant negative proteins before being seeded onto the DRG neurons. This allows us to specifically interrogate the roles of these oligodendroglial proteins in regulating myelination. The protocols can also be applied in the study of other cell types, thus providing an approach that allows selective manipulation of proteins expressed by a desired cell type, such as oligodendrocytes for the targeted study of signaling and compensation mechanisms. In conclusion, combining the in vitro myelination assay with lentiviral infected OPCs provides a strategic tool for the analysis of molecular mechanisms involved in myelination.

  12. Influence of myelin proteins on the structure and dynamics of a model membrane with emphasis on the low temperature regime.

    PubMed

    Knoll, W; Peters, J; Kursula, P; Gerelli, Y; Natali, F

    2014-11-28

    Myelin is an insulating, multi-lamellar membrane structure wrapped around selected nerve axons. Increasing the speed of nerve impulses, it is crucial for the proper functioning of the vertebrate nervous system. Human neurodegenerative diseases, such as multiple sclerosis, are linked to damage to the myelin sheath through demyelination. Myelin exhibits a well defined subset of myelin-specific proteins, whose influence on membrane dynamics, i.e., myelin flexibility and stability, has not yet been explored in detail. In a first paper [W. Knoll, J. Peters, P. Kursula, Y. Gerelli, J. Ollivier, B. Demé, M. Telling, E. Kemner, and F. Natali, Soft Matter 10, 519 (2014)] we were able to spotlight, through neutron scattering experiments, the role of peripheral nervous system myelin proteins on membrane stability at room temperature. In particular, the myelin basic protein and peripheral myelin protein 2 were found to synergistically influence the membrane structure while keeping almost unchanged the membrane mobility. Further insight is provided by this work, in which we particularly address the investigation of the membrane flexibility in the low temperature regime. We evidence a different behavior suggesting that the proton dynamics is reduced by the addition of the myelin basic protein accompanied by negligible membrane structural changes. Moreover, we address the importance of correct sample preparation and characterization for the success of the experiment and for the reliability of the obtained results.

  13. Extraversion, neuroticism and strength of the nervous system.

    PubMed

    Frigon, J Y

    1976-11-01

    The hypothesized identity of the dimensions of extraversion-introversion and strength of the nervous system was tested on four groups of nine subjects (neurotic extraverts, stable extraverts, neurotic introverts, stable introverts). Strength of the subjects' nervous system was estimated using the electroencephalographic (EEG) variant of extinction with reinforcement. Introverted subjects were found to have weak nervous systems, according to the EEG index, while extraverted subjects had strong nervous systems, thus confirming the hypothesis. It was also found that the dimension of strength of the nervous system was unrelated to differences in neuroticism. The results are interpreted as adding support to Eysenck's theory relating differences in extraversion-introversion to differences in cortical arousal.

  14. G protein-coupled receptor 37 is a negative regulator of oligodendrocyte differentiation and myelination

    PubMed Central

    Yang, Hyun-Jeong; Vainshtein, Anna; Maik-Rachline, Galia; Peles, Elior

    2016-01-01

    While the formation of myelin by oligodendrocytes is critical for the function of the central nervous system, the molecular mechanism controlling oligodendrocyte differentiation remains largely unknown. Here we identify G protein-coupled receptor 37 (GPR37) as an inhibitor of late-stage oligodendrocyte differentiation and myelination. GPR37 is enriched in oligodendrocytes and its expression increases during their differentiation into myelin forming cells. Genetic deletion of Gpr37 does not affect the number of oligodendrocyte precursor cells, but results in precocious oligodendrocyte differentiation and hypermyelination. The inhibition of oligodendrocyte differentiation by GPR37 is mediated by suppression of an exchange protein activated by cAMP (EPAC)-dependent activation of Raf-MAPK-ERK1/2 module and nuclear translocation of ERK1/2. Our data suggest that GPR37 regulates central nervous system myelination by controlling the transition from early-differentiated to mature oligodendrocytes. PMID:26961174

  15. G protein-coupled receptor 37 is a negative regulator of oligodendrocyte differentiation and myelination.

    PubMed

    Yang, Hyun-Jeong; Vainshtein, Anna; Maik-Rachline, Galia; Peles, Elior

    2016-01-01

    While the formation of myelin by oligodendrocytes is critical for the function of the central nervous system, the molecular mechanism controlling oligodendrocyte differentiation remains largely unknown. Here we identify G protein-coupled receptor 37 (GPR37) as an inhibitor of late-stage oligodendrocyte differentiation and myelination. GPR37 is enriched in oligodendrocytes and its expression increases during their differentiation into myelin forming cells. Genetic deletion of Gpr37 does not affect the number of oligodendrocyte precursor cells, but results in precocious oligodendrocyte differentiation and hypermyelination. The inhibition of oligodendrocyte differentiation by GPR37 is mediated by suppression of an exchange protein activated by cAMP (EPAC)-dependent activation of Raf-MAPK-ERK1/2 module and nuclear translocation of ERK1/2. Our data suggest that GPR37 regulates central nervous system myelination by controlling the transition from early-differentiated to mature oligodendrocytes.

  16. Radiation response of the central nervous system

    SciTech Connect

    Schultheiss, T.E.; Kun, L.E.; Stephens, L.C.

    1995-03-30

    This report reviews the anatomical, pathophysiological, and clinical aspects of radiation injury to the central nervous system (CNS). Despite the lack of pathoGyomonic characteristics for CNS radiation lesions, demyelination and malacia are consistently the dominant morphological features of radiation myelopathy. In addition, cerebral atrophy is commonly observed in patients with neurological deficits related to chemotherapy and radiation, and neurocognitive deficits are associated with diffuse white matter changes. Clinical and experimental dose-response information have been evaluated and summarized into specific recommendations for the spinal cord and brain. The common spinal cord dose limit of 45 Gn in 22 to 25 fractions is conservative and can be relaxed if respecting this limit materially reduces the probability of tumor control. It is suggested that the 5% incidence of radiation myelopathy probably lies between 57 and 61 Gy to the spinal cord in the absence of dose modifying chemotherapy. A clinically detectable length effect for the spinal cord has not been observed. The effects of chemotherapy and altered fractionation are also discussed. Brain necrosis in adults is rarely noted below 60 Gy in conventional fractionation, with imaging and clinical changes being observed generally only above 50 Gy. However, neurocognitive effects are observed at lower doses, especially in children. A more pronounced volume effect is believed to exist in the brain than in the spinal cord. Tumor progression may be hard to distinguish from radiation and chemotherapy effects. Diffuse white matter injury can be attributed to radiation and associated with neurological deficits, but leukoencephalopathy is rarely observed in the absence of chemotherapy. Subjective, objective, management, and analytic (SOMA) parameters related to radiation spinal cord and brain injury have been developed and presented on ordinal scales. 140 refs., 3 figs., 6 tabs.

  17. Mechanosensitivity in the enteric nervous system

    PubMed Central

    Mazzuoli-Weber, Gemma; Schemann, Michael

    2015-01-01

    The enteric nervous system (ENS) autonomously controls gut muscle activity. Mechanosensitive enteric neurons (MEN) initiate reflex activity by responding to mechanical deformation of the gastrointestinal wall. MEN throughout the gut primarily respond to compression or stretch rather than to shear force. Some MEN are multimodal as they respond to compression and stretch. Depending on the region up to 60% of the entire ENS population responds to mechanical stress. MEN fire action potentials after mechanical stimulation of processes or soma although they are more sensitive to process deformation. There are at least two populations of MEN based on their sensitivity to different modalities of mechanical stress and on their firing pattern. (1) Rapidly, slowly and ultra-slowly adapting neurons which encode compressive forces. (2) Ultra-slowly adapting stretch-sensitive neurons encoding tensile forces. Rapid adaptation of firing is typically observed after compressive force while slow adaptation or ongoing spike discharge occurs often during tensile stress (stretch). All MEN have some common properties: they receive synaptic input, are low fidelity mechanoreceptors and are multifunctional in that some serve interneuronal others even motor functions. Consequently, MEN possess processes with mechanosensitive as well as efferent functions. This raises the intriguing hypothesis that MEN sense and control muscle activity at the same time as servo-feedback loop. The mechanosensitive channel(s) or receptor(s) expressed by the different MEN populations are unknown. Future concepts have to incorporate compressive and tensile-sensitive MEN into neural circuits that controls muscle activity. They may interact to control various forms of a particular motor pattern or regulate different motor patterns independently from each other. PMID:26528136

  18. Carbon monoxide and the nervous system.

    PubMed

    Raub, J A; Benignus, V A

    2002-12-01

    Carbon monoxide (CO) is a colorless, tasteless, odorless, and non-irritating gas formed when carbon in fuel is not burned completely. It enters the bloodstream through the lungs and attaches to hemoglobin (Hb), the body's oxygen carrier, forming carboxyhemoglobin (COHb) and thereby reducing oxygen (O(2)) delivery to the body's organs and tissues. High COHb concentrations are poisonous. Central nervous system (CNS) effects in individuals suffering acute CO poisoning cover a wide range, depending on severity of exposure: headache, dizziness, weakness, nausea, vomiting, disorientation, confusion, collapse, and coma. At lower concentrations, CNS effects include reduction in visual perception, manual dexterity, learning, driving performance, and attention level. Earlier work is frequently cited to justify the statement that CO exposure sufficient to produce COHb levels of ca. 5% would be sufficient to produce visual sensitivity reduction and various neurobehavioral performance deficits. In a recent literature re-evaluation, however, the best estimate was that [COHb] would have to rise to 15-20% before a 10% reduction in any behavioral or visual measurement could be observed. This conclusion was based on (1) critical review of the literature on behavioral and sensory effects, (2) review and interpretation of the physiological effects of COHb on the CNS, (3) extrapolation from the effects of hypoxic hypoxia to the effects of CO hypoxia, and (4) extrapolation from rat behavioral effects of CO to humans. Also covered in this review article are effects of chronic CO exposure, the discovery of neuroglobin, a summary of the relatively new role for endogenous CO in neurotransmission and vascular homeostasis, groups which might be especially sensitive to CO, and recommendations on further research. The interested reader is directed to other published reviews of the literature on CO and historically seminal references that form our understanding of this ubiquitous gas. PMID

  19. Is There Anything "Autonomous" in the Nervous System?

    ERIC Educational Resources Information Center

    Rasia-Filho, Alberto A.

    2006-01-01

    The terms "autonomous" or "vegetative" are currently used to identify one part of the nervous system composed of sympathetic, parasympathetic, and gastrointestinal divisions. However, the concepts that are under the literal meaning of these words can lead to misconceptions about the actual nervous organization. Some clear-cut examples indicate…

  20. BMP7 retards peripheral myelination by activating p38 MAPK in Schwann cells

    PubMed Central

    Liu, Xiaoyu; Zhao, Yahong; Peng, Su; Zhang, Shuqiang; Wang, Meihong; Chen, Yeyue; Zhang, Shan; Yang, Yumin; Sun, Cheng

    2016-01-01

    Schwann cell (SC) myelination is pivotal for the proper physiological functioning of the nervous system, but the underlying molecular mechanism remains less well understood. Here, we showed that the expression of bone morphogenetic protein 7 (BMP7) inversely correlates with myelin gene expression during peripheral myelination, which suggests that BMP7 is likely a negative regulator for myelin gene expression. Our experiments further showed that the application of BMP7 attenuates the cAMP induced myelin gene expression in SCs. Downstream pathway analysis suggested that both p38 MAPK and SMAD are activated by exogenous BMP7 in SCs. The pharmacological intervention and gene silence studies revealed that p38 MAPK, not SMAD, is responsible for BMP7-mediated suppression of myelin gene expression. In addition, c-Jun, a potential negative regulator for peripheral myelination, was up-regulated by BMP7. In vivo experiments showed that BMP7 treatment greatly impaired peripheral myelination in newborn rats. Together, our results established that BMP7 is a negative regulator for peripheral myelin gene expression and that p38 MAPK/c-Jun axis might be the main downstream target of BMP7 in this process. PMID:27491681

  1. BMP7 retards peripheral myelination by activating p38 MAPK in Schwann cells.

    PubMed

    Liu, Xiaoyu; Zhao, Yahong; Peng, Su; Zhang, Shuqiang; Wang, Meihong; Chen, Yeyue; Zhang, Shan; Yang, Yumin; Sun, Cheng

    2016-08-05

    Schwann cell (SC) myelination is pivotal for the proper physiological functioning of the nervous system, but the underlying molecular mechanism remains less well understood. Here, we showed that the expression of bone morphogenetic protein 7 (BMP7) inversely correlates with myelin gene expression during peripheral myelination, which suggests that BMP7 is likely a negative regulator for myelin gene expression. Our experiments further showed that the application of BMP7 attenuates the cAMP induced myelin gene expression in SCs. Downstream pathway analysis suggested that both p38 MAPK and SMAD are activated by exogenous BMP7 in SCs. The pharmacological intervention and gene silence studies revealed that p38 MAPK, not SMAD, is responsible for BMP7-mediated suppression of myelin gene expression. In addition, c-Jun, a potential negative regulator for peripheral myelination, was up-regulated by BMP7. In vivo experiments showed that BMP7 treatment greatly impaired peripheral myelination in newborn rats. Together, our results established that BMP7 is a negative regulator for peripheral myelin gene expression and that p38 MAPK/c-Jun axis might be the main downstream target of BMP7 in this process.

  2. Arf6 guanine-nucleotide exchange factor cytohesin-2 regulates myelination in nerves.

    PubMed

    Torii, Tomohiro; Ohno, Nobuhiko; Miyamoto, Yuki; Kawahara, Kazuko; Saitoh, Yurika; Nakamura, Kazuaki; Takashima, Shou; Sakagami, Hiroyuki; Tanoue, Akito; Yamauchi, Junji

    2015-05-01

    In postnatal development of the peripheral nervous system (PNS), Schwann cells differentiate to insulate neuronal axons with myelin sheaths, increasing the nerve conduction velocity. To produce the mature myelin sheath with its multiple layers, Schwann cells undergo dynamic morphological changes. While extracellular molecules such as growth factors and cell adhesion ligands are known to regulate the myelination process, the intracellular molecular mechanism underlying myelination remains unclear. In this study, we have produced Schwann cell-specific conditional knockout mice for cytohesin-2, a guanine-nucleotide exchange factor (GEF) specifically activating Arf6. Arf6, a member of the Ras-like protein family, participates in various cellular functions including cell morphological changes. Cytohesin-2 knockout mice exhibit decreased Arf6 activity and reduced myelin thickness in the sciatic nerves, with decreased expression levels of myelin protein zero (MPZ), the major myelin marker protein. These results are consistent with those of experiments in which Schwann cell-neuronal cultures were treated with pan-cytohesin inhibitor SecinH3. On the other hand, the numbers of Ki67-positive cells in knockout mice and controls are comparable, indicating that cytohesin-2 does not have a positive effect on cell numbers. Thus, signaling through cytohesin-2 is required for myelination by Schwann cells, and cytohesin-2 is added to the list of molecules known to underlie PNS myelination.

  3. Evolution of the CNS myelin gene regulatory program.

    PubMed

    Li, Huiliang; Richardson, William D

    2016-06-15

    Myelin is a specialized subcellular structure that evolved uniquely in vertebrates. A myelinated axon conducts action potentials many times faster than an unmyelinated axon of the same diameter; for the same conduction speed, the unmyelinated axon would need a much larger diameter and volume than its myelinated counterpart. Hence myelin speeds information transfer and saves space, allowing the evolution of a powerful yet portable brain. Myelination in the central nervous system (CNS) is controlled by a gene regulatory program that features a number of master transcriptional regulators including Olig1, Olig2 and Myrf. Olig family genes evolved from a single ancestral gene in non-chordates. Olig2, which executes multiple functions with regard to oligodendrocyte identity and development in vertebrates, might have evolved functional versatility through post-translational modification, especially phosphorylation, as illustrated by its evolutionarily conserved serine/threonine phospho-acceptor sites and its accumulation of serine residues during more recent stages of vertebrate evolution. Olig1, derived from a duplicated copy of Olig2 in early bony fish, is involved in oligodendrocyte development and is critical to remyelination in bony vertebrates, but is lost in birds. The origin of Myrf orthologs might be the result of DNA integration between an invading phage or bacterium and an early protist, producing a fusion protein capable of self-cleavage and DNA binding. Myrf seems to have adopted new functions in early vertebrates - initiation of the CNS myelination program as well as the maintenance of mature oligodendrocyte identity and myelin structure - by developing new ways to interact with DNA motifs specific to myelin genes. This article is part of a Special Issue entitled SI: Myelin Evolution.

  4. Wallerian Degeneration in Central Nervous System: Dynamic Associations between Diffusion Indices and Their Underlying Pathology

    PubMed Central

    Piao, Yueshan; Guo, Deyu; Zhu, Zixin; Tian, Xin; Li, Kuncheng; Yu, Chunshui

    2012-01-01

    Background Although diffusion tensor imaging has been used to monitor Wallerian degeneration, the exact relationship between the evolution of diffusion indices and its underlying pathology, especially in central nervous system, remains largely unknown. Here we aimed to address this question using a cat Wallerian degeneration model of corticospinal tract. Methodology/Principal Findings Twenty-five domestic mature Felis catus were included in the present study. The evolution of diffusion indices, including mean diffusivity (MD), fractional anisotropy (FA), primary (λ1) and transverse eigenvalues (λ23) of the degenerated corticospinal tract, were observed at baseline (before modeling) and at 2, 4, 6, 8, 10, 15, 20, 25, 30, 45 and 60 days after modeling in 4 cats. Pathological examinations were performed at eight time points mentioned above. Wallerian degeneration can be detected as early as the 2nd day after modeling by both diffusion tensor imaging and pathology. According to the evolution of diffusion indices, Wallerian degeneration can be classified into 2 stages. During the early stage (within 8 days after modeling), progressive disintegration of axons and myelin sheaths underlies the decreases in FA and λ1 and the increase in λ23. However, during the late stage (after 8 days), the gradual increases in FA, MD and λ1 and the unchanged λ23 seem to be a comprehensive reflection of the pathological processes including microglia activation, myelin clearance, and astrocytosis. Conclusions/Significance Our findings help the understanding of the altered diffusion indices in the context of pathology and suggest that diffusion tensor imaging has the potential to monitor the processes of Wallerian degeneration in the central nervous system in vivo after acute damage. PMID:22829950

  5. General Information about Childhood Central Nervous System Embryonal Tumors

    MedlinePlus

    ... System Embryonal Tumors Treatment (PDQ®)–Patient Version General Information About Childhood Central Nervous System Embryonal Tumors Go ... in patients with a high-risk tumor. The information from tests and procedures done to detect (find) ...

  6. Animal-microbe interactions and the evolution of nervous systems.

    PubMed

    Eisthen, Heather L; Theis, Kevin R

    2016-01-01

    Animals ubiquitously interact with environmental and symbiotic microbes, and the effects of these interactions on animal physiology are currently the subject of intense interest. Nevertheless, the influence of microbes on nervous system evolution has been largely ignored. We illustrate here how taking microbes into account might enrich our ideas about the evolution of nervous systems. For example, microbes are involved in animals' communicative, defensive, predatory and dispersal behaviours, and have likely influenced the evolution of chemo- and photosensory systems. In addition, we speculate that the need to regulate interactions with microbes at the epithelial surface may have contributed to the evolutionary internalization of the nervous system.

  7. Calretinin in the peripheral nervous system of the adult zebrafish

    PubMed Central

    Levanti, M B; Montalbano, G; Laurà, R; Ciriaco, E; Cobo, T; García-Suarez, O; Germanà, A; Vega, J A

    2008-01-01

    Calretinin is a calcium-binding protein found widely distributed in the central nervous system and chemosensory cells of the teleosts, but its presence in the peripheral nervous system of fishes is unknown. In this study we used Western blot analysis and immunohistochemistry to investigate the occurrence and distribution of calretinin in the cranial nerve ganglia, dorsal root ganglia, sympathetic ganglia, and enteric nervous system of the adult zebrafish. By Western blotting a unique and specific protein band with an estimated molecular weight of around 30 kDa was detected, and it was identified as calretinin. Immunohistochemistry revealed that calretinin is selectively present in the cytoplasm of the neurons and never in the satellite glial cells. In both sensory and sympathetic ganglia the density of neurons that were immunolabelled, their size and morphology, as well as the intensity of immunostaining developed within the cytoplasm, were heterogeneous. In the enteric nervous system calretinin immunoreactivity was detected in a subset of enteric neurons as well as in a nerve fibre plexus localized inside the muscular layers. The present results demonstrate that in addition to the central nervous system, calretinin is also present in the peripheral nervous system of zebrafish, and contribute to completing the map of the distribution of this protein in the nervous system of teleosts. PMID:18173770

  8. [Systemic lupus erythematosus and the central nervous system].

    PubMed

    Rojas, E; Orrea Solano, M

    1993-01-01

    The central nervous system (CNS) manifestations of the chronic autoimmune disease systemic lupus erythematous (SLE) are reviewed. SLE-CNS dysfunction is broadly divided into neurologic and psychiatric clinical categories. The distinct clinical entities within these broad categories are fully described. Diagnostic criteria employed to verify the presence of SLE-CNS dysfunction, including laboratory serum and cerebral spinal fluid analyses as well as radiologic and other multimodality diagnostic tools, are compared and contrasted with respect to sensitivity and specificity.

  9. The Human Sympathetic Nervous System Response to Spaceflight

    NASA Technical Reports Server (NTRS)

    Ertl, Andrew C.; Diedrich, Andre; Paranjape, Sachin Y.; Biaggioni, Italo; Robertson, Rose Marie; Lane, Lynda D.; Shiavi, Richard; Robertson, David

    2003-01-01

    The sympathetic nervous system is an important part of the autonomic (or automatic) nervous system. When an individual stands up, the sympathetic nervous system speeds the heart and constricts blood vessels to prevent a drop in blood pressure. A significant number of astronauts experience a drop in blood pressure when standing for prolonged periods after they return from spaceflight. Difficulty maintaining blood pressure with standing is also a daily problem for many patients. Indirect evidence available before the Neurolab mission suggested the problem in astronauts while in space might be due partially to reduced sympathetic nervous system activity. The purpose of this experiment was to identify whether sympathetic activity was reduced during spaceflight. Sympathetic nervous system activity can be determined in part by measuring heart rate, nerve activity going to blood vessels, and the release of the hormone norepinephrine into the blood. Norepinephrine is a neurotransmitter discharged from active sympathetic nerve terminals, so its rate of release can serve as a marker of sympathetic nervous system action. In addition to standard cardiovascular measurements (heart rate, blood pressure), we determined sympathetic nerve activity as well as norepinephrine release and clearance on four crewmembers on the Neurolab mission. Contrary to our expectation, the results demonstrated that the astronauts had mildly elevated resting sympathetic nervous system activity in space. Sympathetic nervous system responses to stresses that simulated the cardiovascular effects of standing (lower body negative pressure) were brisk both during and after spaceflight. We concluded that, in the astronauts tested, the activity and response of the sympathetic nervous system to cardiovascular stresses appeared intact and mildly elevated both during and after spaceflight. These changes returned to normal within a few days.

  10. Oligodendrocyte, Astrocyte, and Microglia Crosstalk in Myelin Development, Damage, and Repair.

    PubMed

    Domingues, Helena S; Portugal, Camila C; Socodato, Renato; Relvas, João B

    2016-01-01

    Oligodendrocytes are the myelinating glia of the central nervous system. Myelination of axons allows rapid saltatory conduction of nerve impulses and contributes to axonal integrity. Devastating neurological deficits caused by demyelinating diseases, such as multiple sclerosis, illustrate well the importance of the process. In this review, we focus on the positive and negative interactions between oligodendrocytes, astrocytes, and microglia during developmental myelination and remyelination. Even though many lines of evidence support a crucial role for glia crosstalk during these processes, the nature of such interactions is often neglected when designing therapeutics for repair of demyelinated lesions. Understanding the cellular and molecular mechanisms underlying glial cell communication and how they influence oligodendrocyte differentiation and myelination is fundamental to uncover novel therapeutic strategies for myelin repair. PMID:27551677

  11. Oligodendrocyte, Astrocyte, and Microglia Crosstalk in Myelin Development, Damage, and Repair

    PubMed Central

    Domingues, Helena S.; Portugal, Camila C.; Socodato, Renato; Relvas, João B.

    2016-01-01

    Oligodendrocytes are the myelinating glia of the central nervous system. Myelination of axons allows rapid saltatory conduction of nerve impulses and contributes to axonal integrity. Devastating neurological deficits caused by demyelinating diseases, such as multiple sclerosis, illustrate well the importance of the process. In this review, we focus on the positive and negative interactions between oligodendrocytes, astrocytes, and microglia during developmental myelination and remyelination. Even though many lines of evidence support a crucial role for glia crosstalk during these processes, the nature of such interactions is often neglected when designing therapeutics for repair of demyelinated lesions. Understanding the cellular and molecular mechanisms underlying glial cell communication and how they influence oligodendrocyte differentiation and myelination is fundamental to uncover novel therapeutic strategies for myelin repair. PMID:27551677

  12. Evolution of eumetazoan nervous systems: insights from cnidarians

    PubMed Central

    Kelava, Iva; Rentzsch, Fabian; Technau, Ulrich

    2015-01-01

    Cnidarians, the sister group to bilaterians, have a simple diffuse nervous system. This morphological simplicity and their phylogenetic position make them a crucial group in the study of the evolution of the nervous system. The development of their nervous systems is of particular interest, as by uncovering the genetic programme that underlies it, and comparing it with the bilaterian developmental programme, it is possible to make assumptions about the genes and processes involved in the development of ancestral nervous systems. Recent advances in sequencing methods, genetic interference techniques and transgenic technology have enabled us to get a first glimpse into the molecular network underlying the development of a cnidarian nervous system—in particular the nervous system of the anthozoan Nematostella vectensis. It appears that much of the genetic network of the nervous system development is partly conserved between cnidarians and bilaterians, with Wnt and bone morphogenetic protein (BMP) signalling, and Sox genes playing a crucial part in the differentiation of neurons. However, cnidarians possess some specific characteristics, and further studies are necessary to elucidate the full regulatory network. The work on cnidarian neurogenesis further accentuates the need to study non-model organisms in order to gain insights into processes that shaped present-day lineages during the course of evolution. PMID:26554048

  13. Bacterial meningitis and other nonviral infections of the nervous system.

    PubMed

    Bleck, Thomas P

    2013-10-01

    Bacteria and fungi, owing to their intrinsic properties and the host responses they produce, result in relatively specific clinical syndromes when they infect the central nervous system. The infecting organism may produce symptoms and signs by interfering with the function of the nervous system tissue being invaded or compressed. The definitive treatment of central nervous system infection depends on correct identification and antimicrobial treatment of the infecting organism, relief of excessive pressure or mass effect that it exerts, and modulation of the host's immune response to allow clearance of the organism while minimizing excessive inflammation. PMID:24094387

  14. Disseminated encephalomyelitis-like central nervous system neoplasm in childhood.

    PubMed

    Zhao, Jianhui; Bao, Xinhua; Fu, Na; Ye, Jintang; Li, Ting; Yuan, Yun; Zhang, Chunyu; Zhang, Yao; Zhang, Yuehua; Qin, Jiong; Wu, Xiru

    2014-08-01

    A malignant neoplasm in the central nervous system with diffuse white matter changes on magnetic resonance imaging (MRI) is rare in children. It could be misdiagnosed as acute disseminated encephalomyelitis. This report presents our experience based on 4 patients (3 male, 1 female; aged 7-13 years) whose MRI showed diffuse lesions in white matter and who were initially diagnosed with acute disseminated encephalomyelitis. All of the patients received corticosteroid therapy. After brain biopsy, the patients were diagnosed with gliomatosis cerebri, primitive neuroectodermal tumor and central nervous system lymphoma. We also provide literature reviews and discuss the differentiation of central nervous system neoplasm from acute disseminated encephalomyelitis.

  15. Pharmacotherapy for Adults with Tumors of the Central Nervous System

    PubMed Central

    Schor, Nina F.

    2009-01-01

    Tumors of the adult central nervous system are among the most common and most chemoresistant neoplasms. Malignant tumors of the brain and spinal cord collectively account for approximately 1.3% of all cancers and 2.2% of all cancer-related deaths. Novel pharmacological approaches to nervous system tumors are urgently needed. This review presents the current approaches and challenges to successful pharmacotherapy of adults with malignant tumors of the central nervous system and discusses novel approaches aimed at overcoming these challenges. PMID:19091301

  16. Ultrasonic Transduction of DNA into Central Nervous System Cells

    NASA Astrophysics Data System (ADS)

    Manome, Yoshinobu; Nakayama, Naoto; Furuhata, Hiroshi

    2005-03-01

    Many diseases involving the central nervous system are intractable to conventional therapies, thereby requiring an alternative treatment such as gene therapy. Therapy requires safety since the central nervous system is a critical organ. The choice of non-viral vectors, such as naked plasmid DNA, may have merit. However, transduction efficiencies of these vectors are low. We have investigated the use of ultrasound and found that insonation effectively enhanced transduction of naked plasmid DNA into cultured slices of mouse brain. Since ultrasound successfully facilitated the transduction of naked plasmid DNA into the neural tissue, this approach may have a role in gene therapy for the central nervous system.

  17. Hematopoietic progenitors express myelin basic protein and ensheath axons in Shiverer brain.

    PubMed

    Goolsby, James; Makar, Tapas; Dhib-Jalbut, Suhayl; Bever, Christopher T; Pessac, Bernard; Trisler, David

    2013-04-15

    Oligodendroglia are cells of the central nervous system (CNS) that form myelin sheath, which insulates neuronal axons. Neuropathologies of the CNS include dysmyelination of axons in multiple sclerosis and CNS trauma. Cell replacement is a promising but largely untested therapy for dysmyelination. Shiverer mouse, a genetic mutant that does not synthesize full-length myelin basic protein (MBP), a critical prerequisite protein in CNS myelin sheath formation, provides an unequivocal model for determining the potential of stem cells to become oligodendroglia. We demonstrate that adult wild-type mouse bone marrow stem cells can express MBP and ensheath axons when transplanted into Shiverer brain.

  18. The evolution of vertebrate and invertebrate myelin: a theoretical computational study.

    PubMed

    Castelfranco, Ann M; Hartline, Daniel K

    2015-06-01

    Multilayered, lipid-rich myelin increases nerve impulse conduction velocity, contributes to compact nervous systems, and reduces metabolic costs of neural activity. Based on the hypothesis that increased impulse conduction velocity provides a selective advantage that drives the evolution of myelin, we simulated a sequence of plausible intermediate stages of myelin evolution, each of which providing an enhancement of conduction speed. We started with the expansion of insulating glial coverage, which led first to a single layer of myelin surrounding the axon and then to multiple myelin wraps with well-organized nodes. The myelinated fiber was modeled at three levels of complexity as the hypothesized evolutionary progression became more quantitatively exacting: 1) representing the fiber as a mathematically-tractable uniform active cylinder with the effect of myelination approximated by changing its specific capacitance (C(m)); 2) representing it as a chain of simple, cable-model compartments having alternating nodal and internodal parameters subject to optimization, and 3) representing it in a double cable model with the axon and myelin sheath treated separately. Conduction velocity was optimized at each stage. To maintain optimal conduction velocities, increased myelin coverage of axonal surface must be accompanied by an increase in channel density at the evolving nodes, but along with increases in myelin thickness, a reduction in overall average channel density must occur. Leakage under the myelin sheath becomes more of a problem with smaller fiber diameters, which may help explain the tendency for myelin to occur preferentially in larger nerve fibers in both vertebrates and invertebrates.

  19. Individual Neuronal Subtypes Exhibit Diversity in CNS Myelination Mediated by Synaptic Vesicle Release.

    PubMed

    Koudelka, Sigrid; Voas, Matthew G; Almeida, Rafael G; Baraban, Marion; Soetaert, Jan; Meyer, Martin P; Talbot, William S; Lyons, David A

    2016-06-01

    Regulation of myelination by oligodendrocytes in the CNS has important consequences for higher-order nervous system function (e.g., [1-4]), and there is growing consensus that neuronal activity regulates CNS myelination (e.g., [5-9]) through local axon-oligodendrocyte synaptic-vesicle-release-mediated signaling [10-12]. Recent analyses have indicated that myelination along axons of distinct neuronal subtypes can differ [13, 14], but it is not known whether regulation of myelination by activity is common to all neuronal subtypes or only some. This limits insight into how specific neurons regulate their own conduction. Here, we use a novel fluorescent fusion protein reporter to study myelination along the axons of distinct neuronal subtypes over time in zebrafish. We find that the axons of reticulospinal and commissural primary ascending (CoPA) neurons are among the first myelinated in the zebrafish CNS. To investigate how activity regulates myelination by different neuronal subtypes, we express tetanus toxin (TeNT) in individual reticulospinal or CoPA neurons to prevent synaptic vesicle release. We find that the axons of individual tetanus toxin expressing reticulospinal neurons have fewer myelin sheaths than controls and that their myelin sheaths are 50% shorter than controls. In stark contrast, myelination along tetanus-toxin-expressing CoPA neuron axons is entirely normal. These results indicate that while some neuronal subtypes modulate myelination by synaptic vesicle release to a striking degree in vivo, others do not. These data have implications for our understanding of how different neurons regulate myelination and thus their own function within specific neuronal circuits.

  20. Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold

    PubMed Central

    Noseda, Roberta; Guerrero-Valero, Marta; Alberizzi, Valeria; Previtali, Stefano C.; Sherman, Diane L.; Palmisano, Marilena; Huganir, Richard L.; Nave, Klaus-Armin; Cuenda, Ana; Feltri, Maria Laura; Brophy, Peter J.; Bolino, Alessandra

    2016-01-01

    Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS) and central nervous system (CNS) myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK)-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1), a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K)/v-AKT murine thymoma viral oncogene homolog (AKT) pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS. PMID:27070899

  1. Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold.

    PubMed

    Noseda, Roberta; Guerrero-Valero, Marta; Alberizzi, Valeria; Previtali, Stefano C; Sherman, Diane L; Palmisano, Marilena; Huganir, Richard L; Nave, Klaus-Armin; Cuenda, Ana; Feltri, Maria Laura; Brophy, Peter J; Bolino, Alessandra

    2016-04-01

    Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS) and central nervous system (CNS) myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK)-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1), a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K)/v-AKT murine thymoma viral oncogene homolog (AKT) pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS. PMID:27070899

  2. Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold.

    PubMed

    Noseda, Roberta; Guerrero-Valero, Marta; Alberizzi, Valeria; Previtali, Stefano C; Sherman, Diane L; Palmisano, Marilena; Huganir, Richard L; Nave, Klaus-Armin; Cuenda, Ana; Feltri, Maria Laura; Brophy, Peter J; Bolino, Alessandra

    2016-04-01

    Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS) and central nervous system (CNS) myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK)-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1), a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K)/v-AKT murine thymoma viral oncogene homolog (AKT) pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS.

  3. The sympathetic nervous system alterations in human hypertension.

    PubMed

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-03-13

    Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

  4. Reinforcement concept in investigations on simple nervous systems.

    PubMed

    Balaban, P M

    1997-01-01

    An analysis of the applicability of the concept of reinforcement to the studies of learning in simple nervous systems of invertebrates is made. Analysis of the literature data and my own results suggests that reinforcement cannot be regarded as an independent behavioral phenomenon. A description of reinforcement as a state of the nervous system which precedes long-term changes of behavior is given. Using the example of aversive conditioning to food in gastropod snails it is shown that a state of the network that can be correlated with the state of reinforcement can be elicited in the simple nervous system by activation of serotonergic pedal cells modulating avoidance behavior of the animal. The conclusion is made that with certain limitations the reinforcement concept can be used in studies on simple nervous systems.

  5. Complex Homology and the Evolution of Nervous Systems

    PubMed Central

    Liebeskind, Benjamin J.; Hillis, David M.; Zakon, Harold H.; Hofmann, Hans A.

    2016-01-01

    We examine the complex evolution of animal nervous systems and discuss the ramifications of this complexity for inferring the nature of early animals. Although reconstructing the origins of nervous systems remains a central challenge in biology, and the phenotypic complexity of early animals remains controversial, a compelling picture is emerging. We now know that the nervous system and other key animal innovations contain a large degree of homoplasy, at least on the molecular level. Conflicting hypotheses about early nervous system evolution are due primarily to differences in the interpretation of this homoplasy. We highlight the need for explicit discussion of assumptions and discuss the limitations of current approaches for inferring ancient phenotypic states. PMID:26746806

  6. [Microglial cells and development of the embryonic central nervous system].

    PubMed

    Legendre, Pascal; Le Corronc, Hervé

    2014-02-01

    Microglia cells are the macrophages of the central nervous system with a crucial function in the homeostasis of the adult brain. However, recent studies showed that microglial cells may also have important functions during early embryonic central nervous system development. In this review we summarize recent works on the extra embryonic origin of microglia, their progenitor niche, the pattern of their invasion of the embryonic central nervous system and on interactions between embryonic microglia and their local environment during invasion. We describe microglial functions during development of embryonic neuronal networks, including their roles in neurogenesis, in angiogenesis and developmental cell death. These recent discoveries open a new field of research on the functions of neural-microglial interactions during the development of the embryonic central nervous system.

  7. Source characterization of nervous system active pharmaceutical ingredients in healthcare wastewaters

    EPA Science Inventory

    Nervous system active pharmaceutical ingredients (APIs), including anti-depressants and opioids, are important clinically administered pharmaceuticals within healthcare facilities. Concentrations and mass loadings of ten nervous system APIs and three nervous system API metaboli...

  8. Introduction to 'Origin and evolution of the nervous system'.

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2015-12-19

    In 1665, Robert Hooke demonstrated in Micrographia the power of the microscope and comparative observations, one of which revealed similarities between the arthropod and vertebrate eyes. Utilizing comparative observations, Saint-Hilaire in 1822 was the first to propose that the ventral nervous system of arthropods corresponds to the dorsal nervous system of vertebrates. Since then, studies on the origin and evolution of the nervous system have become inseparable from studies about Metazoan origins and the origins of organ systems. The advent of genome sequence data and, in turn, phylogenomics and phylogenetics have refined cladistics and expanded our understanding of Metazoan phylogeny. However, the origin and evolution of the nervous system is still obscure and many questions and problems remain. A recurrent problem is whether and to what extent sequence data provide reliable guidance for comparisons across phyla. Are genetic data congruent with the geological fossil records? How can we reconcile evolved character loss with phylogenomic records? And how informative are genetic data in relation to the specification of nervous system morphologies? These provide some of the background and context for a Royal Society meeting to discuss new data and concepts that might achieve insights into the origin and evolution of brains and nervous systems. PMID:26554035

  9. Introduction to 'Origin and evolution of the nervous system'.

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2015-12-19

    In 1665, Robert Hooke demonstrated in Micrographia the power of the microscope and comparative observations, one of which revealed similarities between the arthropod and vertebrate eyes. Utilizing comparative observations, Saint-Hilaire in 1822 was the first to propose that the ventral nervous system of arthropods corresponds to the dorsal nervous system of vertebrates. Since then, studies on the origin and evolution of the nervous system have become inseparable from studies about Metazoan origins and the origins of organ systems. The advent of genome sequence data and, in turn, phylogenomics and phylogenetics have refined cladistics and expanded our understanding of Metazoan phylogeny. However, the origin and evolution of the nervous system is still obscure and many questions and problems remain. A recurrent problem is whether and to what extent sequence data provide reliable guidance for comparisons across phyla. Are genetic data congruent with the geological fossil records? How can we reconcile evolved character loss with phylogenomic records? And how informative are genetic data in relation to the specification of nervous system morphologies? These provide some of the background and context for a Royal Society meeting to discuss new data and concepts that might achieve insights into the origin and evolution of brains and nervous systems.

  10. A single origin of the central nervous system?

    PubMed

    Telford, Maximilian J

    2007-04-20

    As Denes et al. (2007) reveal in this issue, the expression profile and roles of genes that pattern the nervous system in embryos of chordates and annelids are surprisingly similar. This extraordinary conservation suggests that the patterning mechanism has been inherited largely unchanged from the bilaterian common ancestor and that the central nervous system, although dorsal in fish and ventral in worms, is an ancient characteristic of animals. PMID:17448982

  11. A simple analogy for nervous system plasticity after injury.

    PubMed

    Fouad, Karim; Forero, Juan; Hurd, Caitlin

    2015-04-01

    When considering plasticity, the central nervous system can be viewed as a building block house. After damage, building components might be lost or loosened and may be rearranged by renovation, analogous to neuroplasticity that occurs after central nervous system injury. In both scenarios, the location and severity of damage will determine the efficacy of renovation/rehabilitation and thus the quality of the adapted structure.

  12. Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features

    PubMed Central

    Heidari, M; Johnstone, D M; Bassett, B; Graham, R M; Chua, A C G; House, M J; Collingwood, J F; Bettencourt, C; Houlden, H; Ryten, M; Olynyk, J K; Trinder, D; Milward, E A

    2016-01-01

    The ‘neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe−/− × Tfr2mut brain (P=0.002, n ≥5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P<0.04, n ≥5/group) for five other NBIA genes, phospholipase A2 group VI, fatty acid 2-hydroxylase, ceruloplasmin, chromosome 19 open reading frame 12 and ATPase type 13A2. Apart from the ferroxidase ceruloplasmin, all are involved in myelin homeostasis; 16 other myelin-related genes also showed reduced expression (P<0.05), although gross myelin structure and integrity appear unaffected (P>0.05). Overlap (P<0.0001) of differentially expressed genes in Hfe−/− × Tfr2mut brain with human gene co-expression networks suggests iron loading influences expression of NBIA-related and myelin-related genes co-expressed in normal human basal ganglia. There was overlap (P<0.0001) of genes differentially expressed in Hfe−/− × Tfr2mut brain and post-mortem NBIA basal ganglia. Hfe−/− × Tfr2mut mice were hyperactive (P<0.0112) without apparent cognitive impairment by IntelliCage testing (P>0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments. PMID:26728570

  13. Central nervous system adaptation to exercise training

    NASA Astrophysics Data System (ADS)

    Kaminski, Lois Anne

    Exercise training causes physiological changes in skeletal muscle that results in enhanced performance in humans and animals. Despite numerous studies on exercise effects on skeletal muscle, relatively little is known about adaptive changes in the central nervous system. This study investigated whether spinal pathways that mediate locomotor activity undergo functional adaptation after 28 days of exercise training. Ventral horn spinal cord expression of calcitonin gene-related peptide (CGRP), a trophic factor at the neuromuscular junction, choline acetyltransferase (Chat), the synthetic enzyme for acetylcholine, vesicular acetylcholine transporter (Vacht), a transporter of ACh into synaptic vesicles and calcineurin (CaN), a protein phosphatase that phosphorylates ion channels and exocytosis machinery were measured to determine if changes in expression occurred in response to physical activity. Expression of these proteins was determined by western blot and immunohistochemistry (IHC). Comparisons between sedentary controls and animals that underwent either endurance training or resistance training were made. Control rats received no exercise other than normal cage activity. Endurance-trained rats were exercised 6 days/wk at 31m/min on a treadmill (8% incline) for 100 minutes. Resistance-trained rats supported their weight plus an additional load (70--80% body weight) on a 60° incline (3 x 3 min, 5 days/wk). CGRP expression was measured by radioimmunoassay (RIA). CGRP expression in the spinal dorsal and ventral horn of exercise-trained animals was not significantly different than controls. Chat expression measured by Western blot and IHC was not significantly different between runners and controls but expression in resistance-trained animals assayed by IHC was significantly less than controls and runners. Vacht and CaN immunoreactivity in motor neurons of endurance-trained rats was significantly elevated relative to control and resistance-trained animals. Ventral

  14. Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis.

    PubMed

    Díaz-Balzac, Carlos A; Lázaro-Peña, María I; Vázquez-Figueroa, Lionel D; Díaz-Balzac, Roberto J; García-Arrarás, José E

    2016-01-01

    The Echinodermata comprise an interesting branch in the phylogenetic tree of deuterostomes. Their radial symmetry which is reflected in their nervous system anatomy makes them a target of interest in the study of nervous system evolution. Until recently, the study of the echinoderm nervous system has been hindered by a shortage of neuronal markers. However, in recent years several markers of neuronal and fiber subpopulations have been described. These have been used to identify subpopulations of neurons and fibers, but an integrative study of the anatomical relationship of these subpopulations is wanting. We have now used eight commercial antibodies, together with three antibodies produced by our group to provide a comprehensive and integrated description and new details of the echinoderm neuroanatomy using the holothurian Holothuria glaberrima (Selenka, 1867) as our model system. Immunoreactivity of the markers used showed: (1) specific labeling patterns by markers in the radial nerve cords, which suggest the presence of specific nerve tracts in holothurians. (2) Nerves directly innervate most muscle fibers in the longitudinal muscles. (3) Similar to other deuterostomes (mainly vertebrates), their enteric nervous system is composed of a large and diverse repertoire of neurons and fiber phenotypes. Our results provide a first blueprint of the anatomical organization of cells and fibers that form the holothurian neural circuitry, and highlight the fact that the echinoderm nervous system shows unexpected diversity in cell and fiber types and their distribution in both central and peripheral nervous components.

  15. Global research priorities for infections that affect the nervous system

    PubMed Central

    John, Chandy C.; Carabin, Hélène; Montano, Silvia M.; Bangirana, Paul; Zunt, Joseph R.; Peterson, Phillip K.

    2015-01-01

    Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries. PMID:26580325

  16. Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis.

    PubMed

    Díaz-Balzac, Carlos A; Lázaro-Peña, María I; Vázquez-Figueroa, Lionel D; Díaz-Balzac, Roberto J; García-Arrarás, José E

    2016-01-01

    The Echinodermata comprise an interesting branch in the phylogenetic tree of deuterostomes. Their radial symmetry which is reflected in their nervous system anatomy makes them a target of interest in the study of nervous system evolution. Until recently, the study of the echinoderm nervous system has been hindered by a shortage of neuronal markers. However, in recent years several markers of neuronal and fiber subpopulations have been described. These have been used to identify subpopulations of neurons and fibers, but an integrative study of the anatomical relationship of these subpopulations is wanting. We have now used eight commercial antibodies, together with three antibodies produced by our group to provide a comprehensive and integrated description and new details of the echinoderm neuroanatomy using the holothurian Holothuria glaberrima (Selenka, 1867) as our model system. Immunoreactivity of the markers used showed: (1) specific labeling patterns by markers in the radial nerve cords, which suggest the presence of specific nerve tracts in holothurians. (2) Nerves directly innervate most muscle fibers in the longitudinal muscles. (3) Similar to other deuterostomes (mainly vertebrates), their enteric nervous system is composed of a large and diverse repertoire of neurons and fiber phenotypes. Our results provide a first blueprint of the anatomical organization of cells and fibers that form the holothurian neural circuitry, and highlight the fact that the echinoderm nervous system shows unexpected diversity in cell and fiber types and their distribution in both central and peripheral nervous components. PMID:26987052

  17. Global research priorities for infections that affect the nervous system.

    PubMed

    John, Chandy C; Carabin, Hélène; Montano, Silvia M; Bangirana, Paul; Zunt, Joseph R; Peterson, Phillip K

    2015-11-19

    Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries.

  18. Global research priorities for infections that affect the nervous system.

    PubMed

    John, Chandy C; Carabin, Hélène; Montano, Silvia M; Bangirana, Paul; Zunt, Joseph R; Peterson, Phillip K

    2015-11-19

    Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries. PMID:26580325

  19. Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis

    PubMed Central

    Díaz-Balzac, Carlos A.; Lázaro-Peña, María I.; Vázquez-Figueroa, Lionel D.; Díaz-Balzac, Roberto J.; García-Arrarás, José E.

    2016-01-01

    The Echinodermata comprise an interesting branch in the phylogenetic tree of deuterostomes. Their radial symmetry which is reflected in their nervous system anatomy makes them a target of interest in the study of nervous system evolution. Until recently, the study of the echinoderm nervous system has been hindered by a shortage of neuronal markers. However, in recent years several markers of neuronal and fiber subpopulations have been described. These have been used to identify subpopulations of neurons and fibers, but an integrative study of the anatomical relationship of these subpopulations is wanting. We have now used eight commercial antibodies, together with three antibodies produced by our group to provide a comprehensive and integrated description and new details of the echinoderm neuroanatomy using the holothurian Holothuria glaberrima (Selenka, 1867) as our model system. Immunoreactivity of the markers used showed: (1) specific labeling patterns by markers in the radial nerve cords, which suggest the presence of specific nerve tracts in holothurians. (2) Nerves directly innervate most muscle fibers in the longitudinal muscles. (3) Similar to other deuterostomes (mainly vertebrates), their enteric nervous system is composed of a large and diverse repertoire of neurons and fiber phenotypes. Our results provide a first blueprint of the anatomical organization of cells and fibers that form the holothurian neural circuitry, and highlight the fact that the echinoderm nervous system shows unexpected diversity in cell and fiber types and their distribution in both central and peripheral nervous components. PMID:26987052

  20. Susceptibility of inbred mice to chronic central nervous system infection by Theiler's murine encephalomyelitis virus.

    PubMed

    Lipton, H L; Dal Canto, M C

    1979-10-01

    The present study demonstrated that the clinicopathological expression of the late demyelinating disease due to chronic central nervous system infection by Theiler's mouse encephalomyelitis virus was dependent, at least in part, on the strain of mouse used as host. A range of involvement was observed, with late disease being most severe in the SJL strain, intermediate in the CBA and C3H/He strains, and least in C57BL/6 mice. The lack of clinical signs in seven other inbred strains of mice indicates that their response to chronic infection was similar to C57BL/6 mice. SJL, CBA, C3H/He, and C57BL/6 mice all generated similar levels of neutralizing antibody. A correlation between the severity of late disease and central nervous system virus content was not demonstrated, which indirectly suggests an immunopathological rather than a cytolytic mechanism of myelin injury during the late disease period. Finally, in addition to being more extensive, SJL demyelinating lesions contained a disproportionately large number of macrophages compared with those of similar lesions in CBA and C3H/He mice.

  1. Peripheral Nervous System Genes Expressed in Central Neurons Induce Growth on Inhibitory Substrates

    PubMed Central

    Buchser, William J.; Smith, Robin P.; Pardinas, Jose R.; Haddox, Candace L.; Hutson, Thomas; Moon, Lawrence; Hoffman, Stanley R.; Bixby, John L.; Lemmon, Vance P.

    2012-01-01

    Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS’s enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons. PMID:22701605

  2. The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system

    PubMed Central

    Mueller, Bernhard K; Yamashita, Toshihide; Schaffar, Gregor; Mueller, Reinhold

    2006-01-01

    During the development of the nervous system, outgrowing axons often have to travel long distances to reach their target neurons. In this process, outgrowing neurites tipped with motile growth cones rely on guidance cues present in their local environment. These cues are detected by specific receptors expressed on growth cones and neurites and influence the trajectory of the growing fibres. Neurite growth, guidance, target innervation and synapse formation and maturation are the processes that occur predominantly but not exclusively during embryonic or early post-natal development in vertebrates. As a result, a functional neural network is established, which is usually remarkably stable. However, the stability of the neural network in higher vertebrates comes at an expensive price, i.e. the loss of any significant ability to regenerate injured or damaged neuronal connections in their central nervous system (CNS). Most importantly, neurite growth inhibitors prevent any regenerative growth of injured nerve fibres. Some of these inhibitors are associated with CNS myelin, others are found at the lesion site and in the scar tissue. Traumatic injuries in brain and spinal cord of mammals induce upregulation of embryonic inhibitory or repulsive guidance cues and their receptors on the neurites. An example for embryonic repulsive directional cues re-expressed at lesion sites in both the rat and human CNS is provided with repulsive guidance molecules, a new family of directional guidance cues. PMID:16939972

  3. Therapeutic Application of Electric Fields in the Injured Nervous System.

    PubMed

    Haan, Niels; Song, Bing

    2014-02-01

    Significance: Nervous system injuries, both in the peripheral nervous system (PNS) and central nervous system are a major cause for pain, loss-of-function, and impairment of daily life. As nervous system injuries commonly heal slowly or incompletely, new therapeutic approaches may be required. Recent Advances: The observation that cultured neurons are able to respond to exogenous electric fields (EFs) by sprouting more neurites and directing growth along the field, along with the presence of endogenous EFs in the developing vertebrate nervous system have led to the suggestion of the use of EFs in a regenerative therapeutic setting. This review discusses the effects of EFs on nervous cells, and their use in the treatment of nervous injuries in the eye, limb nerves, and the spinal cord. Exogenous EFs have been shown to be neuroprotective in various injury models of the eye, including traumatic injury, congenital degenerative retinopathy, and glaucoma. In the PNS, EFs are able to stimulate regrowth and functional recovery in damaged limb nerves. In the spinal cord, axonal regeneration and improved quality of life may be achieved using EF stimulation. Critical Issues: The optimal paradigm for electrical stimulation has not been determined, and the mechanisms behind the effect of EF are still largely unknown. Future Directions: Although the therapeutic use of EFs in the nervous system is still in its infancy, it is a promising therapeutic avenue for otherwise hard to treat injuries. The cellular/molecular mechanisms of such regulation need to be fully investigated, and the efficiency of applied EFs during wound healing needs to be optimized in a systematic approach in both animal models and future clinical trials. PMID:24761356

  4. Vascular endothelial growth factor in central nervous system injuries - a vascular growth factor getting nervous?

    PubMed

    Sköld, Mattias K; Kanje, Martin

    2008-11-01

    Vascular Endothelial Growth Factor (VEGF) is recognized as a central factor in growth, survival and permeability of blood vessels in both physiological and pathological conditions. It is as such of importance for vascular responses in various central nervous system (CNS) disorders. Accumulating evidence suggest that VEGF may also act as a neuroprotective and neurotrophic factor supporting neuronal survival and neuronal regeneration. Findings of neuropilins as shared co-receptors between molecules with such seemingly different functions as the axon guidance molecules semaphorins and VEGF has further boosted the interest in the role of VEGF in neural tissue injury and repair mechanisms. Thus, VEGF most likely act in parallel or concurrent on cells in both the vascular and nervous system. The present review gives a summary of known or potential aspects of the VEGF system in the healthy and diseased nervous system. The potential benefits but also problems and pitfalls in intervening in the actions of such a multifunctional factor as VEGF in the disordered CNS are also covered.

  5. Reactions of the nervous system to magnetic fields

    NASA Technical Reports Server (NTRS)

    Kholodov, Y. A.

    1974-01-01

    This magnetobiological survey considers sensory, nervous, stress and genetic effects of magnetic fields on man and animals. It is shown that the nervous system plays an important role in the reactions of the organism to magnetic fields; the final biological effect is a function of the strength of the magnetic fields, the gradient, direction of the lines of force, duration and location of the action, and the functional status of the organism.

  6. Structural and functional features of central nervous system lymphatic vessels.

    PubMed

    Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J; Eccles, Jacob D; Rouhani, Sherin J; Peske, J David; Derecki, Noel C; Castle, David; Mandell, James W; Lee, Kevin S; Harris, Tajie H; Kipnis, Jonathan

    2015-07-16

    One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

  7. Assessment of the peripheral, central, and autonomic nervous system function in styrene workers

    SciTech Connect

    Murata, K.; Araki, S.; Yokoyama, K. )

    1991-01-01

    To investigate the effects of styrene exposure on peripheral, central, and autonomic nervous system functions in man, we measured the distribution of nerve conduction velocities (DCV), short-latency somatosensory evoked potentials (SSEP), and variability in electrocardiographic R-R interval (CVRR) as well as conventional sensory and motor median nerve conduction velocities (SCV and MCV) in eleven styrene-exposed workers. The styrene workers' urinary phenylglyoxylic acid levels ranged from 31 to 419 (mean 169) mg/g creatinine at the end of the work shift on the examination day (estimated exposure to styrene of 22 ppm in air). Control subjects, matched to each styrene worker by sex and age, were selected from healthy adults without cardiovascular, neurologic and other potentially confounding disorders. In the styrene workers, we found that the V80 velocity of the DCV, below which 80% of active nerve fibers lie, and the SCV were both significantly slowed; the CVRR was also significantly reduced. There were no significant differences in SSEP latencies, MCV, or heart rate between the exposed workers and controls. These data, despite the small sample size, suggest that styrene affects the faster myelinated fibers of the peripheral sensory nerves, and that it also affects autonomic nervous activity.

  8. Reorganization of Lipid Diffusion by Myelin Basic Protein as Revealed by STED Nanoscopy.

    PubMed

    Steshenko, Olena; Andrade, Débora M; Honigmann, Alf; Mueller, Veronika; Schneider, Falk; Sezgin, Erdinc; Hell, Stefan W; Simons, Mikael; Eggeling, Christian

    2016-06-01

    Myelin is a multilayered membrane that ensheathes axonal fibers in the vertebrate nervous system, allowing fast propagation of nerve action potentials. It contains densely packed lipids, lacks an actin-based cytocortex, and requires myelin basic protein (MBP) as its major structural component. This protein is the basic constituent of the proteinaceous meshwork that is localized between adjacent cytoplasmic membranes of the myelin sheath. Yet, it is not clear how MBP influences the organization and dynamics of the lipid constituents of myelin. Here, we used optical stimulated emission depletion super-resolution microscopy in combination with fluorescence correlation spectroscopy to assess the characteristics of diffusion of different fluorescent lipid analogs in myelin membrane sheets of cultured oligodendrocytes and in micrometer-sized domains that were induced by MBP in live epithelial PtK2 cells. Lipid diffusion was significantly faster and less anomalous both in oligodendrocytes and inside the MBP-rich domains of PtK2 cells compared with undisturbed live PtK2 cells. Our data show that MBP reorganizes lipid diffusion, possibly by preventing the buildup of an actin-based cytocortex and by preventing most membrane proteins from entering the myelin sheath region. Yet, in contrast to myelin sheets in oligodendrocytes, the MBP-induced domains in epithelial PtK2 cells demonstrate no change in lipid order, indicating that segregation of long-chain lipids into myelin sheets is a process specific to oligodendrocytes. PMID:27276262

  9. Preliminary Evidence of Increased Hippocampal Myelin Content in Veterans with Posttraumatic Stress Disorder

    PubMed Central

    Chao, Linda L.; Tosun, Duygu; Woodward, Steven H.; Kaufer, Daniela; Neylan, Thomas C.

    2015-01-01

    Recent findings suggest the formation of myelin in the central nervous system by oligodendrocytes is a continuous process that can be modified with experience. For example, a recent study showed that immobilization stress increased oligodendrogensis in the dentate gyrus of adult rat hippocampus. Because changes in myelination represents an adaptive form of brain plasticity that has a greater reach in the adult brain than other forms of plasticity (e.g., neurogenesis), the objective of this “proof of concept” study was to examine whether there are differences in myelination in the hippocampi of humans with and without post-traumatic stress disorder (PTSD). We used the ratio of T1-weighted/T2-weighted magnetic resonance image (MRI) intensity to estimate the degree of hippocampal myelination in 19 male veterans with PTSD and 19 matched trauma-exposed male veterans without PTSD (mean age: 43 ± 12 years). We found that veterans with PTSD had significantly more hippocampal myelin than trauma-exposed controls. There was also found a positive correlation between estimates of hippocampal myelination and PTSD and depressive symptom severity. To our knowledge, this is the first study to examine hippocampal myelination in humans with PTSD. These results provide preliminary evidence for stress-induced hippocampal myelin formation as a potential mechanism underlying the brain abnormalities associated with vulnerability to stress. PMID:26696852

  10. Reorganization of Lipid Diffusion by Myelin Basic Protein as Revealed by STED Nanoscopy.

    PubMed

    Steshenko, Olena; Andrade, Débora M; Honigmann, Alf; Mueller, Veronika; Schneider, Falk; Sezgin, Erdinc; Hell, Stefan W; Simons, Mikael; Eggeling, Christian

    2016-06-01

    Myelin is a multilayered membrane that ensheathes axonal fibers in the vertebrate nervous system, allowing fast propagation of nerve action potentials. It contains densely packed lipids, lacks an actin-based cytocortex, and requires myelin basic protein (MBP) as its major structural component. This protein is the basic constituent of the proteinaceous meshwork that is localized between adjacent cytoplasmic membranes of the myelin sheath. Yet, it is not clear how MBP influences the organization and dynamics of the lipid constituents of myelin. Here, we used optical stimulated emission depletion super-resolution microscopy in combination with fluorescence correlation spectroscopy to assess the characteristics of diffusion of different fluorescent lipid analogs in myelin membrane sheets of cultured oligodendrocytes and in micrometer-sized domains that were induced by MBP in live epithelial PtK2 cells. Lipid diffusion was significantly faster and less anomalous both in oligodendrocytes and inside the MBP-rich domains of PtK2 cells compared with undisturbed live PtK2 cells. Our data show that MBP reorganizes lipid diffusion, possibly by preventing the buildup of an actin-based cytocortex and by preventing most membrane proteins from entering the myelin sheath region. Yet, in contrast to myelin sheets in oligodendrocytes, the MBP-induced domains in epithelial PtK2 cells demonstrate no change in lipid order, indicating that segregation of long-chain lipids into myelin sheets is a process specific to oligodendrocytes.

  11. Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling.

    PubMed

    Linneberg, Cecilie; Harboe, Mette; Laursen, Lisbeth S

    2015-01-01

    In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through α6β1 integrin. Here, we identify the Eph-ephrin family of guidance receptors as novel regulators of the initial axo-glia interaction, preceding myelination. We demonstrate that so-called forward and reverse signaling, mediated by members of both Eph and ephrin subfamilies, has distinct and opposing effects on processes extension and myelin sheet formation. EphA forward signaling inhibits oligodendrocyte process extension and myelin sheet formation, and blocking of bidirectional signaling through this receptor enhances myelination. Similarly, EphB forward signaling also reduces myelin membrane formation, but in contrast to EphA forward signaling, this occurs in an integrin-dependent manner, which can be reversed by overexpression of a constitutive active β1-integrin. Furthermore, ephrin-B reverse signaling induced by EphA4 or EphB1 enhances myelin sheet formation. Combined, this suggests that the Eph-ephrin receptors are important mediators of bidirectional signaling between axons and oligodendrocytes. It further implies that balancing Eph-ephrin forward and reverse signaling is important in the selection process of axons to be myelinated.

  12. Systemic delivery to central nervous system by engineered PLGA nanoparticles

    PubMed Central

    Cai, Qiang; Wang, Long; Deng, Gang; Liu, Junhui; Chen, Qianxue; Chen, Zhibiao

    2016-01-01

    Neurological disorders are an important global public health problem, but pharmaceutical treatments are limited due to drug access to the central nervous system being restricted by the blood-brain barrier (BBB). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are one of the most promising drug and gene delivery systems for crossing the BBB. While these systems offer great promise, PLGA NPs also have some intrinsic drawbacks and require further engineering for clinical and research applications. Multiple strategies have been developed for using PLGA NPs to deliver compounds across the BBB. We classify these strategies into three categories according to the adaptations made to the PLGA NPs (1) to facilitate travel from the injection site (pre-transcytosis strategies); (2) to enhance passage across the brain endothelial cells (BBB transcytosis strategies) and (3) to achieve targeting of the impaired nervous system cells (post-transcytosis strategies). PLGA NPs modified according to these three strategies are denoted first, second, and third generation NPs, respectively. We believe that fusing these three strategies to engineer multifunctional PLGA NPs is the only way to achieve translational applications. PMID:27158367

  13. Monophyletic Origin of the Metazoan Nervous System: Characterizing

    NASA Astrophysics Data System (ADS)

    Watkins, Russell; Beckenbach, Andrew

    In the absence of additional cases to be studied, our understanding of the likelihood of intelligent life evolving elsewhere in the universe must be framed within the context of the evolution of intelligence on this planet. Towards this end a valid model of the evolution of animal life, and in particular of the nervous system, is key. Models which describe the development of complexity within the nervous system can be positively misleading if they are not grounded in an accurate model of the true relationships of the animal phyla. If fact the evolution of animal life at its earliest stages, from protists to the sponges, Cnidaria, and Ctenophora and onward to the bilateral animal phyla is poorly characterized. Recently numerous phylogenies of the early animal radiation have been published based upon DNA sequence data, with conflicting and poorly supported results. A polyphyletic origin for the animal nervous system has been implied by the results of several studies, which would lead to the conclusion that some characteristics of the nervous systems of higher and lower animals could be convergent. We show that an equally parsimonious interpretation of the molecular sequence data published thus far is that it reflects rapid speciation events early in animal evolution among the classical ``diploblast'' phyla, as well as accelerated DNA sequence divergence among the higher animals. This could be interpreted as support for a classical phylogeny of the animal kingdom, and thus of a strictly monophyletic origin for the nervous system.

  14. Evolution of flatworm central nervous systems: Insights from polyclads

    PubMed Central

    Quiroga, Sigmer Y.; Carolina Bonilla, E.; Marcela Bolaños, D.; Carbayo, Fernando; Litvaitis, Marian K.; Brown, Federico D.

    2015-01-01

    The nervous systems of flatworms have diversified extensively as a consequence of the broad range of adaptations in the group. Here we examined the central nervous system (CNS) of 12 species of polyclad flatworms belonging to 11 different families by morphological and histological studies. These comparisons revealed that the overall organization and architecture of polyclad central nervous systems can be classified into three categories (I, II, and III) based on the presence of globuli cell masses -ganglion cells of granular appearance-, the cross-sectional shape of the main nerve cords, and the tissue type surrounding the nerve cords. In addition, four different cell types were identified in polyclad brains based on location and size. We also characterize the serotonergic and FMRFamidergic nervous systems in the cotylean Boninia divae by immunocytochemistry. Although both neurotransmitters were broadly expressed, expression of serotonin was particularly strong in the sucker, whereas FMRFamide was particularly strong in the pharynx. Finally, we test some of the major hypothesized trends during the evolution of the CNS in the phylum by a character state reconstruction based on current understanding of the nervous system across different species of Platyhelminthes and on up-to-date molecular phylogenies. PMID:26500427

  15. Evolution of flatworm central nervous systems: Insights from polyclads.

    PubMed

    Quiroga, Sigmer Y; Carolina Bonilla, E; Marcela Bolaños, D; Carbayo, Fernando; Litvaitis, Marian K; Brown, Federico D

    2015-01-01

    The nervous systems of flatworms have diversified extensively as a consequence of the broad range of adaptations in the group. Here we examined the central nervous system (CNS) of 12 species of polyclad flatworms belonging to 11 different families by morphological and histological studies. These comparisons revealed that the overall organization and architecture of polyclad central nervous systems can be classified into three categories (I, II, and III) based on the presence of globuli cell masses -ganglion cells of granular appearance-, the cross-sectional shape of the main nerve cords, and the tissue type surrounding the nerve cords. In addition, four different cell types were identified in polyclad brains based on location and size. We also characterize the serotonergic and FMRFamidergic nervous systems in the cotylean Boninia divae by immunocytochemistry. Although both neurotransmitters were broadly expressed, expression of serotonin was particularly strong in the sucker, whereas FMRFamide was particularly strong in the pharynx. Finally, we test some of the major hypothesized trends during the evolution of the CNS in the phylum by a character state reconstruction based on current understanding of the nervous system across different species of Platyhelminthes and on up-to-date molecular phylogenies.

  16. Directional Spread of Alphaherpesviruses in the Nervous System

    PubMed Central

    Kramer, Tal; Enquist, Lynn W.

    2013-01-01

    Alphaherpesviruses are pathogens that invade the nervous systems of their mammalian hosts. Directional spread of infection in the nervous system is a key component of the viral lifecycle and is critical for the onset of alphaherpesvirus-related diseases. Many alphaherpesvirus infections originate at peripheral sites, such as epithelial tissues, and then enter neurons of the peripheral nervous system (PNS), where lifelong latency is established. Following reactivation from latency and assembly of new viral particles, the infection typically spreads back out towards the periphery. These spread events result in the characteristic lesions (cold sores) commonly associated with herpes simplex virus (HSV) and herpes zoster (shingles) associated with varicella zoster virus (VZV). Occasionally, the infection spreads transsynaptically from the PNS into higher order neurons of the central nervous system (CNS). Spread of infection into the CNS, while rarer in natural hosts, often results in severe consequences, including death. In this review, we discuss the viral and cellular mechanisms that govern directional spread of infection in the nervous system. We focus on the molecular events that mediate long distance directional transport of viral particles in neurons during entry and egress. PMID:23435239

  17. Nongenomic Actions of Adrenal Steroids in the Central Nervous System

    PubMed Central

    Evanson, Nathan K.; Herman, James P.; Sakai, Randall R.; Krause, Eric G.

    2015-01-01

    Mineralocorticoids and glucocorticoids are steroid hormones that are released by the adrenal cortex in response to stress and hydromineral imbalance. Historically, adrenocorticosteroid actions are attributed to effects on gene transcription. More recently, however, it has become clear that genome-independent pathways represent an important facet of adrenal steroid actions. These hormones exert nongenomic effects throughout the body, but a significant portion of their actions are specific to the central nervous system. These actions are mediated by a variety of signalling pathways, and lead to physiologically meaningful events in vitro and in vivo. Here we review nongenomic effects of adrenal steroids in the central nervous system at the levels of behaviour, neural system activity, individual neurone activity, and subcellular signalling activity. A clearer understanding of adrenal steroid activity in the central nervous system will lead to a better ability both to treat human disease, and to reduce side-effects of steroid treatments already in use. PMID:20367759

  18. Molecular mechanisms of acrolein-mediated myelin destruction in CNS trauma and disease.

    PubMed

    Shi, R; Page, J C; Tully, M

    2015-01-01

    Myelin is a critical component of the nervous system facilitating efficient propagation of electrical signals and thus communication between the central and peripheral nervous systems and the organ systems that they innervate throughout the body. In instances of neurotrauma and neurodegenerative disease, injury to myelin is a prominent pathological feature responsible for conduction deficits, and leaves axons vulnerable to damage from noxious compounds. Although the pathological mechanisms underlying myelin loss have yet to be fully characterized, oxidative stress (OS) appears to play a prominent role. Specifically, acrolein, a neurotoxic aldehyde that is both a product and an instigator of OS, has been observed in studies to elicit demyelination through calcium-independent and -dependent mechanisms and also by affecting glutamate uptake and promoting excitotoxicity. Furthermore, pharmacological scavenging of acrolein has demonstrated a neuroprotective effect in animal disease models, by conserving myelin's structural integrity and alleviating functional deficits. This evidence indicates that acrolein may be a key culprit of myelin damage while acrolein scavenging could potentially be a promising therapeutic approach for patients suffering from nervous system trauma and disease.

  19. Transcriptional upregulation of myelin components in spontaneous myelin basic protein-deficient mice.

    PubMed

    Staats, Kim A; Pombal, Diana; Schönefeldt, Susann; Van Helleputte, Lawrence; Maurin, Hervé; Dresselaers, Tom; Govaerts, Kristof; Himmelreich, Uwe; Van Leuven, Fred; Van Den Bosch, Ludo; Dooley, James; Humblet-Baron, Stephanie; Liston, Adrian

    2015-05-01

    Myelin is essential for efficient signal transduction in the nervous system comprising of multiple proteins. The intricacies of the regulation of the formation of myelin, and its components, are not fully understood. Here, we describe the characterization of a novel myelin basic protein (Mbp) mutant mouse, mbp(jive), which spontaneously occurred in our mouse colony. These mice displayed the onset of a shaking gait before 3 weeks of age and seizure onset before 2 months of age. Due to a progressive increase of seizure intensity, mbp(jive) mice experienced premature lethality at around 3 months of age. Mbp mRNA transcript or protein was undetectable and, accordingly, genetic analysis demonstrated a homozygous loss of exons 3 to 6 of Mbp. Peripheral nerve conductance was mostly unimpaired. Additionally, we observed grave structural changes in white matter predominant structures were detected by T1, T2 and diffusion weighted magnetic resonance imaging. We additionally observed that Mbp-deficiency results in an upregulation of Qkl, Mag and Cnp, suggestive of a regulatory feedback mechanism whereby compensatory increases in Qkl have downstream effects on Mag and Cnp. Further research will clarify the role and specifications of this myelin feedback loop, as well as determine its potential role in therapeutic strategies for demyelinating disorders.

  20. Guidance Receptors in the Nervous and Cardiovascular Systems.

    PubMed

    Rubina, K A; Tkachuk, V A

    2015-10-01

    Blood vessels and nervous fibers grow in parallel, for they express similar receptors for chemokine substances. Recently, much attention is being given to studying guidance receptors and their ligands besides the growth factors, cytokines, and chemokines necessary to form structures in the nervous and vascular systems. Such guidance molecules determine trajectory for growing axons and vessels. Guidance molecules include Ephrins and their receptors, Neuropilins and Plexins as receptors for Semaphorins, Robos as receptors for Slit-proteins, and UNC5B receptors binding Netrins. Apart from these receptors and their ligands, urokinase and its receptor (uPAR) and T-cadherin are also classified as guidance molecules. The urokinase system mediates local proteolysis at the leading edge of cells, thereby providing directed migration. T-cadherin is a repellent molecule that regulates the direction of growing axons and blood vessels. Guidance receptors also play an important role in the diseases of the nervous and cardiovascular systems.

  1. Potential Autonomic Nervous System Effects of Statins in Heart Failure

    PubMed Central

    Horwich, Tamara; Middlekauff, Holly

    2008-01-01

    Synopsis Sympathetic nervous system activation in heart failure, as indexed by elevated norepinephrine levels, higher muscle sympathetic nerve activity and reduced heart rate variability, is associated with pathologic ventricular remodeling, increased arrhythmias, sudden death, and increased mortality. Recent evidence suggests that HMG-CoA reductase inhibitor (statin) therapy may provide survival benefit in heart failure of both ischemic and non-ischemic etiology, and one potential mechanism of benefit of statins in heart failure is modulation of the autonomic nervous system. Animal models of heart failure demonstrate reduced sympathetic activation and improved sympathovagal balance with statin therapy. Initial human studies have reported mixed results. Ongoing translational studies and outcomes trials will help delineate the potentially beneficial effects of statins on the autonomic nervous system in heart failure. PMID:18433696

  2. Psychoneuroimmunology--cross-talk between the immune and nervous systems.

    PubMed

    Ziemssen, Tjalf; Kern, Simone

    2007-05-01

    Psychoneuroimmunology is a relatively new field of study that investigates interactions between behaviour and the immune system, mediated by the endocrine and nervous systems. The immune and central nervous system (CNS) maintain extensive communication. On the one hand, the brain modulates the immune system by hardwiring sympathetic and parasympathetic nerves (autonomic nervous system) to lymphoid organs. On the other hand, neuroendocrine hormones such as corticotrophin-releasing hormone or substance P regulate cytokine balance. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and immune system-mediated disease.

  3. Inflammation and cutaneous nervous system involvement in hypertrophic scarring

    PubMed Central

    Li, Shao-hua; Yang, Heng-lian; Xiao, Hu; Wang, Yi-bing; Wang, De-chang; Huo, Ran

    2015-01-01

    This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation. PMID:26692869

  4. Sympathetic nervous system regulation of the tumour microenvironment

    PubMed Central

    Cole, Steven W.; Nagaraja, Archana S.; Lutgendorf, Susan K.; Green, Paige A.; Sood, Anil K.

    2016-01-01

    The peripheral autonomic nervous system (ANS) is known to regulate gene expression in primary tumours and their surrounding microenvironment. Activation of the sympathetic division of the ANS in particular modulates gene expression programs that promote metastasis of solid tumours by stimulating macrophage infiltration, inflammation, angiogenesis, epithelial-mesenchymal transition, and tumour invasion, and by inhibiting cellular immune responses and programmed cell death. Haematological cancers are modulated by sympathetic nervous system (SNS) regulation of stem cell biology and hematopoietic differentiation programs. In addition to identifying a molecular basis for physiologic stress effects on cancer, these findings have also identified new pharmacologic strategies to inhibit cancer progression in vivo. PMID:26299593

  5. Infectious diseases of the nervous system: pathogenesis and worldwide impact.

    PubMed

    Berkhout, Ben

    2008-11-01

    The 2008 Infectious Diseases of the Nervous System: Pathogenesis and World Impact conference was held at the Pasteur Institute of Paris, and was the first worldwide conference on neuroinfections. While viral encephalitis and bacterial meningitis are being actively studied in the developed world, much less attention is paid to the often fatal nervous system infections caused by neurotropic viruses, parasites and mycobacteria that represent important health problems in tropical regions. This meeting fostered worldwide interactions between scientists and stimulated the exchange of the latest research results on these neglected neurotropic pathogens. PMID:18988120

  6. Novel RNA Modifications in the Nervous System: Form and Function

    PubMed Central

    Basanta-Sanchez, Maria; Blanco, Sandra; Li, Jin Billy; Meyer, Kate; Pollock, Jonathan; Sadri-Vakili, Ghazaleh; Rybak-Wolf, Agnieszka

    2014-01-01

    Modified RNA molecules have recently been shown to regulate nervous system functions. This mini-review and associated mini-symposium provide an overview of the types and known functions of novel modified RNAs in the nervous system, including covalently modified RNAs, edited RNAs, and circular RNAs. We discuss basic molecular mechanisms involving RNA modifications as well as the impact of modified RNAs and their regulation on neuronal processes and disorders, including neural fate specification, intellectual disability, neurodegeneration, dopamine neuron function, and substance use disorders. PMID:25392485

  7. [CENTRAL NERVOUS SYSTEM INVOLVEMENT IN GRANULOMATOSIS WITH POLYANGIITIS (GPA)].

    PubMed

    Horovitz, Yuval; Lidar, Merav

    2015-05-01

    We present the case of a 75 year-old female with Wegener's Granulomatosis. The patient arrived intubated to the emergency room, following loss of consciousness and a generalized seizure. A magnetic resonance imaging brain scan revealed a space occupying lesion (SOL) in the right temporal region. Subsequent investigation indicated the SOL to be a primary lymphoma of the central nervous system. The clinical manifestations of granulomatosis with polyangiitis on both the central and peripheral nervous systems are reviewed herein, as well as the appropriated treatment modalities and the link between this disease and various malignancies. PMID:26168637

  8. Central nervous system manifestations of Angiostrongylus cantonensis infection

    PubMed Central

    Martins, Yuri C.; Tanowitz, Herbert B.; Kazacos, Kevin R.

    2014-01-01

    Over 20 species of Angiostrongylus have been described from around the world, but only Angiostrongylus cantonensis has been confirmed to cause central nervous system disease in humans. A neurotropic parasite that matures in the pulmonary arteries of rats, A. cantonensis is the most common cause of eosinophilic meningitis in southern Asia and the Pacific and Caribbean islands. The parasite can also cause encephalitis/encephalomyelitis and rarely ocular angiostrongyliasis. The present paper reviews the life cycle, epidemiology, pathogenesis, clinical features, diagnosis, treatment, prevention and prognosis of A. cantonesis infection. Emphasis is given on the spectrum of central nervous system manifestations and disease pathogenesis. PMID:25312338

  9. Transplantation of Glial Cells Enhances Action Potential Conduction of Amyelinated Spinal Cord Axons in the Myelin-Deficient Rat

    NASA Astrophysics Data System (ADS)

    Utzschneider, David A.; Archer, David R.; Kocsis, Jeffery D.; Waxman, Stephen G.; Duncan, Ian D.

    1994-01-01

    A central issue in transplantation research is to determine how and when transplantation of neural tissue can influence the development and function of the mammalian central nervous system. Of particular interest is whether electrophysiological function in the traumatized or diseased mammalian central nervous system can be improved by the replacement of cellular elements that are missing or damaged. Although it is known that transplantation of neural tissue can lead to functional improvement in models of neurological disease characterized by neuronal loss, less is known about results of transplantation in disorders of myelin. We report here that transplantation of glial cells into the dorsal columns of neonatal myelin-deficient rat spinal cords leads to myelination and a 3-fold increase in conduction velocity. We also show that impulses can propagate into and out of the transplant region and that axons myelinated by transplanted cells do not have impaired frequency-response properties. These results demonstrate that myelination following central nervous system glial cell transplantation enhances action potential conduction in myelin-deficient axons, with conduction velocity approaching normal values.

  10. Thymosin beta4 promotes oligodendrogenesis in the demyelinating central nervous system.

    PubMed

    Zhang, Jing; Zhang, Zheng Gang; Li, Yi; Lu, Mei; Zhang, Yi; Elias, Stanton B; Chopp, Michael

    2016-04-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). No effective remyelination therapies are in use. We hypothesized that thymosin beta4 (Tβ4) is an effective remyelination treatment by promoting differentiation of oligodendrocyte progenitor cells (OPCs), and that the epidermal growth factor receptor (EGFR) signaling pathway contributes to this process. Two demyelination animal models were employed in this study: 1) experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE mice were treated daily for 30days, with Tβ4 or saline treatment initiated on the day of EAE onset; and 2) cuprizone diet model, a non-inflammatory demyelination model. The mice were treated daily for 4weeks with Tβ4 or saline after fed a cuprizone diet for 5weeks. Immunofluorescent staining and Western blot were performed to measure the differentiation of OPCs, myelin and axons, respectively. To obtain insight into mechanisms of action, the expression and activation of the EGFR pathway was measured. AG1478, an EGFR inhibitor, was employed in a loss-of-function study. Data revealed that animals in both demyelination models exhibited significant reduction of myelin basic protein (MBP(+)) levels and CNPase(+) oligodendrocytes. Treatment of EAE mice with Tβ4 significantly improved neurological outcome. Double immunofluorescent staining showed that Tβ4 significantly increased the number of newly generated oligodendrocytes identified by BrdU(+)/CNPase(+) cells and MBP(+) mature oligodendrocytes, and reduced axonal damage in the EAE mice compared with the saline treatment. The newly generated mature oligodendrocytes remyelinated axons, and the increased mature oligodendrocytes significantly correlated with functional improvement (r=0.73, p<0.05). Western blot analysis revealed that Tβ4 treatment increased expression and activation of the EGFR pathway. In the cuprizone demyelination model, Tβ4 treatment was confirmed that significantly

  11. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    NASA Astrophysics Data System (ADS)

    Shumilov, V. N.; Syryamkin, V. I.; Syryamkin, M. V.

    2015-11-01

    The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of

  12. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    SciTech Connect

    Shumilov, V. N. Syryamkin, V. I. Syryamkin, M. V.

    2015-11-17

    The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of

  13. Sympathetic nervous system and inflammation: a conceptual view.

    PubMed

    Jänig, Wilfrid

    2014-05-01

    The peripheral sympathetic nervous system is organized into function-specific pathways that transmit the activity from the central nervous system to its target tissues. The transmission of the impulse activity in the sympathetic ganglia and to the effector tissues is target cell specific and guarantees that the centrally generated command is faithfully transmitted. This is the neurobiological basis of autonomic regulations in which the sympathetic nervous system is involved. Each sympathetic pathway is connected to distinct central circuits in the spinal cord, lower and upper brain stem and hypothalamus. In addition to its conventional functions, the sympathetic nervous system is involved in protection of body tissues against challenges arising from the environment as well as from within the body. This function includes the modulation of inflammation, nociceptors and above all the immune system. Primary and secondary lymphoid organs are innervated by sympathetic postganglionic neurons and processes in the immune tissue are modulated by activity in these sympathetic neurons via adrenoceptors in the membranes of the immune cells (see Bellinger and Lorton, 2014). Are the primary and secondary lymphoid organs innervated by a functionally specific sympathetic pathway that is responsible for the modulation of the functioning of the immune tissue by the brain? Or is this modulation of immune functions a general function of the sympathetic nervous system independent of its specific functions? Which central circuits are involved in the neural regulation of the immune system in the context of neural regulation of body protection? What is the function of the sympatho-adrenal system, involving epinephrine, in the modulation of immune functions? PMID:24525016

  14. Neural Circuit Recording from an Intact Cockroach Nervous System

    PubMed Central

    Titlow, Josh S.; Majeed, Zana R.; Hartman, H. Bernard; Burns, Ellen; Cooper, Robin L.

    2013-01-01

    The cockroach ventral nerve cord preparation is a tractable system for neuroethology experiments, neural network modeling, and testing the physiological effects of insecticides. This article describes the scope of cockroach sensory modalities that can be used to assay how an insect nervous system responds to environmental perturbations. Emphasis here is on the escape behavior mediated by cerci to giant fiber transmission in Periplaneta americana. This in situ preparation requires only moderate dissecting skill and electrophysiological expertise to generate reproducible recordings of neuronal activity. Peptides or other chemical reagents can then be applied directly to the nervous system in solution with the physiological saline. Insecticides could also be administered prior to dissection and the escape circuit can serve as a proxy for the excitable state of the central nervous system. In this context the assays described herein would also be useful to researchers interested in limb regeneration and the evolution of nervous system development for which P. americana is an established model organism. PMID:24300738

  15. Calpain secreted by activated human lymphoid cells degrades myelin.

    PubMed

    Deshpande, R V; Goust, J M; Hogan, E L; Banik, N L

    1995-10-01

    Calpain secreted by lymphoid (MOLT-3, M.R.) or monocytic (U-937, THP-1) cell lines activated with PMA and A23187 degraded myelin antigens. The degradative effect of enzymes released in the extracellular medium was tested on purified myelin basic protein and rat central nervous system myelin in vitro. The extent of protein degradation was determined by SDS-PAGE and densitometric analysis. Various proteinase inhibitors were used to determine to what extent protein degradation was mediated by calpain and/or other enzymes. Lysosomal and serine proteinase inhibitors inhibited 20-40% of the myelin-degradative activity found in the incubation media of cell lines, whereas the calcium chelator (EGTA), the calpain-specific inhibitor (calpastatin), and a monoclonal antibody to m calpain blocked myelin degradation by 60-80%. Since breakdown products of MBP generated by calpain may include fragments with antigenic epitopes, this enzyme may play an important role in the initiation of immune-mediated demyelination. PMID:8568927

  16. MAG, myelin and overcoming growth inhibition in the CNS

    PubMed Central

    McKerracher, Lisa; Rosen, Kenneth M.

    2015-01-01

    While neurons in the central nervous system (CNS) have the capacity to regenerate their axons after injury, they fail to do so, in part because regeneration is limited by growth inhibitory proteins present in CNS myelin. Myelin-associated glycoprotein (MAG) was the first myelin-derived growth inhibitory protein identified, and its inhibitory activity was initially elucidated in 1994 independently by the Filbin lab and the McKerracher lab using cell-based and biochemical techniques, respectively. Since that time we have gained a wealth of knowledge concerning the numerous growth inhibitory proteins that are present in myelin, and we also have dissected many of the neuronal signaling pathways that act as stop signs for axon regeneration. Here we give an overview of the early research efforts that led to the identification of myelin-derived growth inhibitory proteins, and the importance of this family of proteins for understanding neurotrauma and CNS diseases. We further provide an update on how this knowledge has been translated towards current clinical studies in regenerative medicine. PMID:26441514

  17. MicroRNA and Transcriptional Crosstalk in Myelinating Glia

    PubMed Central

    Svaren, John

    2014-01-01

    Several recent studies have addressed the important role of microRNA in regulation of differentiation of myelinating glia. While Schwann cells and oligodendrocytes in the peripheral and central nervous systems, respectively, exhibit significant morphological and regulatory differences, some aspects of transcriptional and microRNA regulation are shared between these two cell types. This review focuses on the intersection of microRNAs with transcriptional regulation in Schwann cell and oligodendrocyte differentiation. In particular, several microRNAs have been shown to modulate expression of critical transcription factors, and in turn, the regulation of microRNA expression is enmeshed within transcriptional networks that coordinate both coding gene and noncoding RNA profiles of myelinating cells. These hubs of regulation control both myelin gene expression as well as the cell cycle transitions of Schwann cells and oligodendrocytes as they terminally differentiate. In addition, some studies have begin to highlight the combinatorial effects of different microRNAs that establish the narrow range of gene regulation required for efficient and stable myelin formation. Overall, the integration of microRNA and transcriptional aspects will help elucidate mechanistic control of the myelination process. PMID:24979526

  18. Immunocytochemical Detection of Acetylcholine in the Rat Central Nervous System

    NASA Astrophysics Data System (ADS)

    Geffard, M.; McRae-Degueurce, A.; Souan, Marie Laure

    1985-07-01

    A specific antibody to acetylcholine was raised and used as a marker for cholinergic neurons in the rat central nervous system. The acetylcholine conjugate was obtained by a two-step immunogen synthesis procedure. An enzyme-linked immunosorbent assay was used to test the specificity and affinity of the antibody in vitro; the results indicated high affinity. A chemical perfusion mixture of allyl alcohol and glutaraldehyde was used to fix the acetylcholine in the nervous tissue. Peroxidase-antiperoxidase immunocytochemistry showed many acetylcholine-immunoreactive cells and fibers in sections from the medial septum region.

  19. The renin-angiotensin system and the central nervous system.

    PubMed

    Ganong, W F

    1977-04-01

    One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons

  20. THE SYMPATHETIC NERVOUS SYSTEM ALTERATIONS IN HUMAN HYPERTENSION

    PubMed Central

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-01-01

    A number of articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as “promoters” and “amplifiers” of human hypertension. We expand on the role of the sympathetic nervous system in two increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

  1. The sympathetic nervous system in hypertension: back to the future?

    PubMed

    Esler, Murray

    2015-02-01

    The seventeenth century London neuroanatomical school headed by Thomas Willis published the first images of the sympathetic nervous system. Nineteenth century European physiologists characterised these as the "pressor nerves". Von Euler's demonstration that the sympathetic transmitter was norepinephrine brought the field into the modern era. Sympathetic nervous system responses are regionally differentiated; human regional sympathetic activity is best studied by recording from postganglionic sympathetic efferents directed to the skeletal muscle vasculature (clinical microneurography) and by measurement of organ-specific norepinephrine release to plasma from sympathetic nerves (regional "norepinephrine spillover"). With these techniques, the sympathetic nervous system became accessible to clinical scientists, allowing the demonstration that sympathetic nervous system activation is crucial in the development and outcomes of cardiovascular disorders, most notably heart failure and essential hypertension. Activation of the renal sympathetic outflow is pivotal in the pathogenesis of essential hypertension. An important goal for clinical scientists is translation of knowledge of pathophysiology, such as this, into better treatment for patients. Although disputed, the case is strong that in hypertension, we are now on the cusp of effective "mechanisms to management" transition, with the use of catheter-based renal sympathetic nerve ablation for treating drug-resistant hypertension.

  2. The nervous and the immune systems: conspicuous physiological analogies.

    PubMed

    Sotelo, Julio

    2015-02-01

    From all biological constituents of complex organisms, two are highly sophisticated: the nervous and the immune systems. Interestingly, their goals and processes appear to be distant from each other; however, their physiological mechanisms keep notorious similarities. Both construct intelligence, learn from experience, and keep memory. Their precise responses to innumerable stimuli are delicately modulated, and the exposure of the individual to thousands of potential challenges integrates their functionality; they use a large part of their constituents not in excitatory activities but in the maintenance of inhibitory mechanisms to keep silent vast intrinsic potentialities. The nervous and immune systems are integrated by a basic cell lineage (neurons and lymphocytes, respectively) but each embodies countless cell subgroups with different and specialized deeds which, in contrast with cells from other organs, labyrinthine molecular arrangements conduct to "one cell, one function". Also, nervous and immune actions confer identity that differentiates every individual from countless others in the same species. Both systems regulate and potentiate their responses aided by countless biological resources of variable intensity: hormones, peptides, cytokines, pro-inflammatory molecules, etc. How the immune and the nervous systems buildup memory, learning capability, and exquisite control of excitatory/inhibitory mechanisms constitute major intellectual challenges for contemporary research.

  3. School Reentry for Children with Acquired Central Nervous Systems Injuries

    ERIC Educational Resources Information Center

    Carney, Joan; Porter, Patricia

    2009-01-01

    Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special…

  4. The Role of Central Nervous System Plasticity in Tinnitus

    ERIC Educational Resources Information Center

    Saunders, James C.

    2007-01-01

    Tinnitus is a vexing disorder of hearing characterized by sound sensations originating in the head without any external stimulation. The specific etiology of these sensations is uncertain but frequently associated with hearing loss. The "neurophysiogical" model of tinnitus has enhanced appreciation of central nervous system (CNS) contributions.…

  5. Nervous System Development and Pattern Preference in Infants.

    ERIC Educational Resources Information Center

    Woodruff, Diana S.; Gerrity, Kathleen M.

    This study examined behavioral correlates of the rapid central nervous system changes occurring in the first 4 months of life. It was hypothesized that during the early months of infancy, visual preference would occur as a function of quantitative dimensions of the stimuli (size) which could be mediated at a subcortical level. It was further…

  6. Neuropathological effects of alcohol on the developing nervous system.

    PubMed

    Lewis, P D

    1985-01-01

    The formation of functional neuronal networks in the developing nervous system is dependent on three mechanisms which have been shown to be susceptible to disturbance by alcohol exposure. These are cell acquisition, cell migration and cellular maturation. Cell acquisition can be reduced by either impaired proliferation or increased cell deletion. Effects of alcohol on cell proliferation, both early in development and in the postnatal cerebellum, are overshadowed by cell loss, which in the cerebellum may affect both small and large neurones. Disturbed cell migration in the developing nervous system is well-known, through neuropathological studies on human fetal alcohol syndrome. Related changes have been produced experimentally in primates, and retarded migration of nerve cells may also occur in the developing cerebellum of the alcohol-exposed rat. Altered nerve cell maturation as shown by examination of dendritic arborisation has been described in the developing hippocampus and brainstem of alcohol-exposed animals. The effects of alcohol on the developing nervous system are unlikely to be specific, and nutritional, hormonal and other pharmacological influences may play a part in their genesis. Moreover, diverse experimental methodology clouds the interpretation of some findings. Although developmental alcohol exposure may have severe and multiple neuropathological effects on the nervous system, reversibility of many lesions, and restoration of functional competence, appears possible in the light of nutritional studies.

  7. Non-central nervous system fetal magnetic resonance imaging.

    PubMed

    Whitby, Elspeth; Wright, Peter

    2015-06-01

    Fetal magnetic resonance imaging (MRI) is currently offered in a limited number of centers but is predominantly used for suspected fetal central nervous system abnormalities. This article concentrates on the role of the different imaging sequences and their value to clinical practice. It also discusses the future of fetal MRI. PMID:26013057

  8. The Nervous System, Science (Experimental): 5363.02.

    ERIC Educational Resources Information Center

    Weiss, Alan; And Others

    This unit of instruction was designed as an intensive in-depth study of the nervous impulse, neurons, brain, spinal cord, and sensory organs. Also included is a study of the endocrine system in its role of maintaining homeostasis. The booklet lists the relevant state-adopted texts and states the performance objectives for the unit. It provides an…

  9. Dopaminergic agents: influence on serotonin in the molluscan nervous system.

    PubMed

    Stefano, G B; Catapane, E; Aiello, E

    1976-10-29

    Treatment of the mussel Mytilus edulis with 6-hydroxydopamine or with alpha-methyl-p-tyrosine decreased dopamine and increased serotonin in the nervous system. Treatment with dopamine decreased serotonin concentrations and prevented the effect of 6-hydroxydopamine. The serotonin concentration appears to be determined in part by the concentration of dopamine. PMID:973139

  10. Homology and Convergence in Vertebrate and Invertebrate Nervous Systems

    NASA Astrophysics Data System (ADS)

    Sandeman, David

    Each year the meeting of the American Neuroscience Society attracts over 20,000 members, reflecting the explosion of interest in this field that has occurred over the past few decades. Researchers from many disciplines are focusing their skills on the investigation of every aspect of nervous systems, and neuroscience now encompasses the entire range of endeavour from the study of the single molecules that make up neural membranes to the non-invasive observation of neural function in animals behaving in their natural environments. Advances over the past three decades in our understanding of nervous systems are impressive and come from a multifaceted approach to the study of both vertebrate and invertebrate animals. An almost unexpected by-product of the parallel investigation of vertebrate and invertebrate nervous systems that is explored in this article is the emergent view of an intricate web of evolutionary homology and convergence exhibited in the structure and function of the nervous systems of these two large, paraphyletic groups of animals.

  11. Homology and convergence in vertebrate and invertebrate nervous systems.

    PubMed

    Sandeman, D

    1999-08-01

    Each year the meeting of the American Neuroscience Society attracts over 20,000 members, reflecting the explosion of interest in this field that has occurred over the past few decades. Researchers from many disciplines are focusing their skills on the investigation of every aspect of nervous systems, and neuroscience now encompasses the entire range of endeavour from the study of the single molecules that make up neural membranes to the non-invasive observation of neural function in animals behaving in their natural environments. Advances over the past three decades in our understanding of nervous systems are impressive and come from a multifaceted approach to the study of both vertebrate and invertebrate animals. An almost unexpected by-product of the parallel investigation of vertebrate and invertebrate nervous systems that is explored in this article is the emergent view of an intricate web of evolutionary homology and convergence exhibited in the structure and function of the nervous systems of these two large, paraphyletic groups of animals.

  12. Membrane interactions in nerve myelin: II. Determination of surface charge from biochemical data.

    PubMed Central

    Inouye, H; Kirschner, D A

    1988-01-01

    In our accompanying paper (Inouye and Kirschner, 1988) we calculated the surface charge density at the extracellular surfaces in peripheral and central nervous system (PNS; CNS) myelins from observations on the dependency of the width of the extracellular space on pH and ionic strength. Here, we have determined the surface charge density of the membrane surfaces in myelin from its chemical composition and the localization of some of its molecular components. We then analyzed the attractive and repulsive forces between the apposed surfaces and calculated equilibrium periods for comparison with the measured values. The biochemical model accounts for the observed isoelectric range of the myelin period and, with the surface charge reduced (possibly by divalent cation binding or a space charge approximation), the model also accounts for the dependency of period on pH above the isoelectric range. At the extracellular (and cytoplasmic) surfaces the contribution of lipid (with pI approximately 2) to the net surface charge is about the same in both PNS and CNS myelin, whereas the contribution of protein depends on which ones are exposed at the two surfaces. The protein conformation and localization modulate the surface charge of the lipid, resulting in positively-charged cytoplasmic surfaces (pI approximately 9) and negatively-charged extracellular surfaces (pI approximately 2-4). The net negative charge at the extracellular surface is due in CNS myelin to lipid, and in PNS myelin to both lipid and (PO) glycoprotein. The net positive charge at the cytoplasmic surface is due in CNS myelin mostly to basic protein, and in PNS myelin to PO glycoprotein and basic protein. The invariance of the cytoplasmic packing may be due to specific short-range interactions. Our models demonstrate how the particular myelin proteins and their localization and conformation can account for the differences in inter-membrane interactions in CNS and PNS myelins. PMID:3345333

  13. Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2

    NASA Astrophysics Data System (ADS)

    Laulumaa, Saara; Kursula, Petri; Natali, Francesca

    2015-01-01

    Myelin is a multilayered proteolipid membrane structure surrounding selected axons in the vertebrate nervous system, which allows the rapid saltatory conduction of nerve impulses. Deficits in myelin formation and maintenance may lead to chronic neurological disease. P2 is an abundant myelin protein from peripheral nerves, binding between two apposing lipid bilayers. We studied the dynamics of the human myelin protein P2 and its mutated P38G variant in hydrated powders using elastic incoherent neutron scattering. The local harmonic vibrations at low temperatures were very similar for both samples, but the mutant protein had increased flexibility and softness close to physiological temperatures. The results indicate that a drastic mutation of proline to glycine at a functional site can affect protein dynamics, and in the case of P2, they may explain functional differences between the two proteins.

  14. Lesioned corticospinal tract axons regenerate in myelin-free rat spinal cord

    SciTech Connect

    Savio, T.; Schwab, M.E. )

    1990-06-01

    In the adult central nervous system (CNS) of higher vertebrates lesioned axons seemed unable to regenerate and reach their former target regions due to influences of the CNS microenvironment. Evidence from in vitro and biochemical experiments has demonstrated the presence of inhibitory substrate components in CNS tissue, in particular in white matter. These CNS components, which strongly inhibit neurite growth, were identified as minor membrane proteins of defined molecular mass (35 and 250 kDa) in oligodendrocyte membranes and CNS myelin. Oligodendrocyte development and myelin formation can be prevented by x-irradiation of newborn rats. Here we show that in myelin-free spinal cords cortico-spinal tract fibers transected at 2 weeks of age show reelongation of many millimeters within 2-3 weeks after the lesion. In normally myelinated controls, regenerative sprouts grew less than 1.7 mm caudal to the lesion.

  15. Lesioned corticospinal tract axons regenerate in myelin-free rat spinal cord.

    PubMed Central

    Savio, T; Schwab, M E

    1990-01-01

    In the adult central nervous system (CNS) of higher vertebrates lesioned axons seemed unable to regenerate and reach their former target regions due to influences of the CNS microenvironment. Evidence from in vitro and biochemical experiments has demonstrated the presence of inhibitory substrate components in CNS tissue, in particular in white matter. These CNS components, which strongly inhibit neurite growth, were identified as minor membrane proteins of defined molecular mass (35 and 250 kDa) in oligodendrocyte membranes and CNS myelin. Oligodendrocyte development and myelin formation can be prevented by x-irradiation of newborn rats. Here we show that in myelin-free spinal cords cortico-spinal tract fibers transected at 2 weeks of age show reelongation of many millimeters within 2-3 weeks after the lesion. In normally myelinated controls, regenerative sprouts grew less than 1.7 mm caudal to the lesion. Images PMID:2349222

  16. The function of RhoGTPases in axon ensheathment and myelination

    PubMed Central

    Feltri, M. Laura; Suter, Ueli; Relvas, João B.

    2008-01-01

    RhoGTPases are molecular switches that integrate extracellular signals to perform diverse cellular responses. This ability relies on the network of proteins regulating RhoGTPases activity and localization, and on the interaction of RhoGTPases with many different cellular effectors. Myelination is an ideal place for RhoGTPases regulation, as it is the result of fine orchestration of many stimuli from at least two cell types. Recent work has revealed that RhoGTPases are required for Schwann cells to sort, ensheath and myelinate axons. Here we will review recent advances showing the critical roles for RhoGTPases in various aspects of Schwann development and myelination, including the recent discovery of their involvement in Charcot-Marie-Tooth disease. Comparison with potential roles of RhoGTPases in central nervous system myelination will be drawn. PMID:18803320

  17. Elements of a 'nervous system' in sponges.

    PubMed

    Leys, Sally P

    2015-02-15

    Genomic and transcriptomic analyses show that sponges possess a large repertoire of genes associated with neuronal processes in other animals, but what is the evidence these are used in a coordination or sensory context in sponges? The very different phylogenetic hypotheses under discussion today suggest very different scenarios for the evolution of tissues and coordination systems in early animals. The sponge genomic 'toolkit' either reflects a simple, pre-neural system used to protect the sponge filter or represents the remnants of a more complex signalling system and sponges have lost cell types, tissues and regionalization to suit their current suspension-feeding habit. Comparative transcriptome data can be informative but need to be assessed in the context of knowledge of sponge tissue structure and physiology. Here, I examine the elements of the sponge neural toolkit including sensory cells, conduction pathways, signalling molecules and the ionic basis of signalling. The elements described do not fit the scheme of a loss of sophistication, but seem rather to reflect an early specialization for suspension feeding, which fits with the presumed ecological framework in which the first animals evolved.

  18. Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling

    PubMed Central

    Hu, Wei; Nessler, Stefan; Hemmer, Bernhard; Eagar, Todd N.; Kane, Lawrence P.; Leliveld, S. Rutger; Müller-Schiffmann, Andreas; Gocke, Anne R.; Lovett-Racke, Amy; Ben, Li-Hong; Hussain, Rehana Z.; Breil, Andreas; Elliott, Jeffrey L.; Puttaparthi, Krishna; Cravens, Petra D.; Singh, Mahendra P.; Petsch, Benjamin; Stitz, Lothar; Racke, Michael K.

    2010-01-01

    The primary biological function of the endogenous cellular prion protein has remained unclear. We investigated its biological function in the generation of cellular immune responses using cellular prion protein gene-specific small interfering ribonucleic acid in vivo and in vitro. Our results were confirmed by blocking cellular prion protein with monovalent antibodies and by using cellular prion protein-deficient and -transgenic mice. In vivo prion protein gene-small interfering ribonucleic acid treatment effects were of limited duration, restricted to secondary lymphoid organs and resulted in a 70% reduction of cellular prion protein expression in leukocytes. Disruption of cellular prion protein signalling augmented antigen-specific activation and proliferation, and enhanced T cell receptor signalling, resulting in zeta-chain-associated protein-70 phosphorylation and nuclear factor of activated T cells/activator protein 1 transcriptional activity. In vivo prion protein gene-small interfering ribonucleic acid treatment promoted T cell differentiation towards pro-inflammatory phenotypes and increased survival of antigen-specific T cells. Cellular prion protein silencing with small interfering ribonucleic acid also resulted in the worsening of actively induced and adoptively transferred experimental autoimmune encephalomyelitis. Finally, treatment of myelin basic protein1–11 T cell receptor transgenic mice with prion protein gene-small interfering ribonucleic acid resulted in spontaneous experimental autoimmune encephalomyelitis. Thus, central nervous system autoimmune disease was modulated at all stages of disease: the generation of the T cell effector response, the elicitation of T effector function and the perpetuation of cellular immune responses. Our findings indicate that cellular prion protein regulates T cell receptor-mediated T cell activation, differentiation and survival. Defects in autoimmunity are restricted to the immune system and not the central

  19. Itch Signaling in the Nervous System

    PubMed Central

    Jeffry, Joseph; Kim, Seungil; Chen, Zhou-Feng

    2013-01-01

    Itch is a major somatic sensation, along with pain, temperature and touch, detected and relayed by the somatosensory system. Itch can be an acute sensation, associated with mosquito bite, or a chronic condition, like atopic dermatitis (29, 59). The origins of the stimulus can be localized in the periphery or systemic, and associated with organ failure or cancer. Itch is also a perception originating in the brain. Itch is broadly characterized as either histamine-dependent (histaminergic) or histamine-independent (nonhistaminergic), both of which are relayed by subsets of C-fibers, and by the second-order neurons expressing gastrin-releasing peptide receptor (GRPR) and spinothalamic track (STT) neurons in the spinal cord of rodents. Historically, itch research has been primarily limited to clinical and psychophysical studies, and to histamine-mediated mechanisms. In contrast, little is known about signaling mechanisms underlying nonhistaminergic itch, despite the fact that the majority of chronic itch are mediated by nonhistaminergic mechanisms. During the past few years, important progress has been made in understanding of molecular signaling of itch, largely due to the introduction of mouse genetics. In this review, we examine some of molecular mechanisms underlying itch sensation with an emphasis on recent studies in rodents. PMID:21841076

  20. The nervous systems of basally branching nemertea (palaeonemertea).

    PubMed

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

    In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks.

  1. The Nervous Systems of Basally Branching Nemertea (Palaeonemertea)

    PubMed Central

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

    In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks. PMID:23785478

  2. The autonomic nervous system at high altitude

    PubMed Central

    Drinkhill, Mark J.; Rivera-Chira, Maria

    2007-01-01

    The effects of hypobaric hypoxia in visitors depend not only on the actual elevation but also on the rate of ascent. Sympathetic activity increases and there are increases in blood pressure and heart rate. Pulmonary vasoconstriction leads to pulmonary hypertension, particularly during exercise. The sympathetic excitation results from hypoxia, partly through chemoreceptor reflexes and partly through altered baroreceptor function. High pulmonary arterial pressures may also cause reflex systemic vasoconstriction. Most permanent high altitude dwellers show excellent adaptation although there are differences between populations in the extent of the ventilatory drive and the erythropoiesis. Some altitude dwellers, particularly Andeans, may develop chronic mountain sickness, the most prominent characteristic of which being excessive polycythaemia. Excessive hypoxia due to peripheral chemoreceptor dysfunction has been suggested as a cause. The hyperviscous blood leads to pulmonary hypertension, symptoms of cerebral hypoperfusion, and eventually right heart failure and death. PMID:17264976

  3. Heterotopic ossification after central nervous system trauma

    PubMed Central

    Sullivan, M. P.; Torres, S. J.; Mehta, S.; Ahn, J.

    2013-01-01

    Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones. PMID:23610702

  4. Temporal Encoding in a Nervous System

    PubMed Central

    Aldworth, Zane N.; Dimitrov, Alexander G.; Cummins, Graham I.; Gedeon, Tomáš; Miller, John P.

    2011-01-01

    We examined the extent to which temporal encoding may be implemented by single neurons in the cercal sensory system of the house cricket Acheta domesticus. We found that these neurons exhibit a greater-than-expected coding capacity, due in part to an increased precision in brief patterns of action potentials. We developed linear and non-linear models for decoding the activity of these neurons. We found that the stimuli associated with short-interval patterns of spikes (ISIs of 8 ms or less) could be predicted better by second-order models as compared to linear models. Finally, we characterized the difference between these linear and second-order models in a low-dimensional subspace, and showed that modification of the linear models along only a few dimensions improved their predictive power to parity with the second order models. Together these results show that single neurons are capable of using temporal patterns of spikes as fundamental symbols in their neural code, and that they communicate specific stimulus distributions to subsequent neural structures. PMID:21573206

  5. Temporal encoding in a nervous system.

    PubMed

    Aldworth, Zane N; Dimitrov, Alexander G; Cummins, Graham I; Gedeon, Tomáš; Miller, John P

    2011-05-01

    We examined the extent to which temporal encoding may be implemented by single neurons in the cercal sensory system of the house cricket Acheta domesticus. We found that these neurons exhibit a greater-than-expected coding capacity, due in part to an increased precision in brief patterns of action potentials. We developed linear and non-linear models for decoding the activity of these neurons. We found that the stimuli associated with short-interval patterns of spikes (ISIs of 8 ms or less) could be predicted better by second-order models as compared to linear models. Finally, we characterized the difference between these linear and second-order models in a low-dimensional subspace, and showed that modification of the linear models along only a few dimensions improved their predictive power to parity with the second order models. Together these results show that single neurons are capable of using temporal patterns of spikes as fundamental symbols in their neural code, and that they communicate specific stimulus distributions to subsequent neural structures.

  6. Claudin-11 Tight Junctions in Myelin Are a Barrier to Diffusion and Lack Strong Adhesive Properties

    PubMed Central

    Denninger, Andrew R.; Breglio, Andrew; Maheras, Kathleen J.; LeDuc, Geraldine; Cristiglio, Viviana; Demé, Bruno; Gow, Alexander; Kirschner, Daniel A.

    2015-01-01

    The radial component is a network of interlamellar tight junctions (TJs) unique to central nervous system myelin. Ablation of claudin-11, a TJ protein, results in the absence of the radial component and compromises the passive electrical properties of myelin. Although TJs are known to regulate paracellular diffusion, this barrier function has not been directly demonstrated for the radial component, and some evidence suggests that the radial component may also mediate adhesion between myelin membranes. To investigate the physical properties of claudin-11 TJs, we compared fresh, unfixed Claudin 11-null and control nerves using x-ray and neutron diffraction. In Claudin 11-null tissue, we detected no changes in myelin structure, stability, or membrane interactions, which argues against the notion that myelin TJs exhibit significant adhesive properties. Moreover, our osmotic stressing and D2O-H2O exchange experiments demonstrate that myelin lacking claudin-11 is more permeable to water and small osmolytes. Thus, our data indicate that the radial component serves primarily as a diffusion barrier and elucidate the mechanism by which TJs govern myelin function. PMID:26445439

  7. Disposition of axonal caspr with respect to glial cell membranes: Implications for the process of myelination.

    PubMed

    Pedraza, Liliana; Huang, Jeffrey K; Colman, David

    2009-11-15

    Neurofascin-155 (NF155) and caspr are transmembrane proteins found at discrete locations early during development of the nervous system. NF155 is present in the oligodendrocyte cell body and processes, whereas caspr is on the axonal surface. In mature nerves, these proteins are clustered at paranodes, flanking the node of Ranvier. To understand how NF155 and caspr become localized to the paranodal regions of myelinated nerves, we have studied their distribution over time in myelinating cultures. Our observations indicate that these two proteins are recruited to the cell surface at the contact zone between axons and oligodendrocytes, where they trans-interact. This association explains the early pattern of caspr distribution, a helical coil that winds around the axon, resembling the turns of the myelin sheath. Caspr, an axonal membrane protein, therefore seems to move in register with the overlying myelinating cell via its interactions with myelin proteins. We suggest that NF155 is the glial cell membrane protein responsible for caspr distribution. The pair act as interacting partners on either side of the axoglial contact area. Most likely, there are other proteins on the axonal surface whose distribution is equally influenced by interaction with the nascent myelin sheath. The fact that caspr follows the movement of the spiraling membrane has a direct affect on the interpretation of the way in which myelin is formed. PMID:19170162

  8. Reduced Myelination and Increased Glia Reactivity Resulting from Severe Neonatal Hyperbilirubinemia.

    PubMed

    Barateiro, Andreia; Chen, Shujuan; Yueh, Mei-Fei; Fernandes, Adelaide; Domingues, Helena Sofia; Relvas, João; Barbier, Olivier; Nguyen, Nghia; Tukey, Robert H; Brites, Dora

    2016-01-01

    Bilirubin-induced neurologic dysfunction (BIND) and kernicterus has been used to describe moderate to severe neurologic dysfunction observed in children exposed to excessive levels of total serum bilirubin (TSB) during the neonatal period. Here we use a new mouse model that targets deletion of the Ugt1 locus and the Ugt1a1 gene in liver to promote hyperbilirubinemia-induced seizures and central nervous system toxicity. The accumulation of TSB in these mice leads to diffuse yellow coloration of brain tissue and a marked cerebellar hypoplasia that we characterize as kernicterus. Histologic studies of brain tissue demonstrate that the onset of severe neonatal hyperbilirubinemia, characterized by seizures, leads to alterations in myelination and glia reactivity. Kernicterus presents as axonopathy with myelination deficits at different brain regions, including pons, medulla oblongata, and cerebellum. The excessive accumulation of TSB in the early neonatal period (5 days after birth) promotes activation of the myelin basic protein (Mbp) gene with an accelerated loss of MBP that correlates with a lack of myelin sheath formation. These changes were accompanied by increased astroglial and microglial reactivity, possibly as a response to myelination injury. Interestingly, cerebellum was the area most affected, with greater myelination impairment and glia burden, and showing a marked loss of Purkinje cells and reduced arborization of the remaining ones. Thus, kernicterus in this model displays not only axonal damage but also myelination deficits and glial activation in different brain regions that are usually related to the neurologic sequelae observed after severe hyperbilirubinemia.

  9. Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination.

    PubMed

    Natrajan, Muktha S; de la Fuente, Alerie G; Crawford, Abbe H; Linehan, Eimear; Nuñez, Vanessa; Johnson, Kory R; Wu, Tianxia; Fitzgerald, Denise C; Ricote, Mercedes; Bielekova, Bibiana; Franklin, Robin J M

    2015-12-01

    The efficiency of central nervous system remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study, we show that expression of genes involved in the retinoid X receptor pathway are decreased with ageing in both myelin-phagocytosing human monocytes and mouse macrophages using a combination of in vivo and in vitro approaches. Disruption of retinoid X receptor function in young macrophages, using the antagonist HX531, mimics ageing by reducing myelin debris uptake. Macrophage-specific RXRα (Rxra) knockout mice revealed that loss of function in young mice caused delayed myelin debris uptake and slowed remyelination after experimentally-induced demyelination. Alternatively, retinoid X receptor agonists partially restored myelin debris phagocytosis in aged macrophages. The agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in multiple sclerosis patient monocytes to a more youthful profile and enhanced myelin debris phagocytosis by patient cells. These results reveal the retinoid X receptor pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.

  10. Claudin-11 Tight Junctions in Myelin Are a Barrier to Diffusion and Lack Strong Adhesive Properties.

    PubMed

    Denninger, Andrew R; Breglio, Andrew; Maheras, Kathleen J; LeDuc, Geraldine; Cristiglio, Viviana; Demé, Bruno; Gow, Alexander; Kirschner, Daniel A

    2015-10-01

    The radial component is a network of interlamellar tight junctions (TJs) unique to central nervous system myelin. Ablation of claudin-11, a TJ protein, results in the absence of the radial component and compromises the passive electrical properties of myelin. Although TJs are known to regulate paracellular diffusion, this barrier function has not been directly demonstrated for the radial component, and some evidence suggests that the radial component may also mediate adhesion between myelin membranes. To investigate the physical properties of claudin-11 TJs, we compared fresh, unfixed Claudin 11-null and control nerves using x-ray and neutron diffraction. In Claudin 11-null tissue, we detected no changes in myelin structure, stability, or membrane interactions, which argues against the notion that myelin TJs exhibit significant adhesive properties. Moreover, our osmotic stressing and D2O-H2O exchange experiments demonstrate that myelin lacking claudin-11 is more permeable to water and small osmolytes. Thus, our data indicate that the radial component serves primarily as a diffusion barrier and elucidate the mechanism by which TJs govern myelin function.

  11. Making myelin basic protein -from mRNA transport to localized translation.

    PubMed

    Müller, Christina; Bauer, Nina M; Schäfer, Isabelle; White, Robin

    2013-09-27

    In the central nervous system (CNS) of most vertebrates, oligodendrocytes enwrap neuronal axons with extensions of their plasma membrane to form the myelin sheath. Several proteins are characteristically found in myelin of which myelin basic protein (MBP) is the second most abundant one after proteolipid protein. The lack of functional MBP in rodents results in a severe hypomyelinated phenotype in the CNS demonstrating its importance for myelin synthesis. Mbp mRNA is transported from the nucleus to the plasma membrane and is translated locally at the axon-glial contact site. Axonal properties such as diameter or electrical activity influence the degree of myelination. As oligodendrocytes can myelinate many axonal segments with varying properties, localized MBP translation represents an important part of a rapid and axon-tailored synthesis machinery. MBP's ability to compact cellular membranes may be problematic for the integrity of intracellular membranous organelles and can also explain why MBP is transported in oligodendrocytes in the form of an mRNA rather than as a protein. Here we review the recent findings regarding intracellular transport and signaling mechanisms leading to localized translation of Mbp mRNA in oligodendrocytes. More detailed insights into the MBP synthesis pathway are important for a better understanding of the myelination process and may foster the development of remyelination therapies for demyelinating diseases.

  12. Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination.

    PubMed

    Chong, S Y Christin; Rosenberg, Sheila S; Fancy, Stephen P J; Zhao, Chao; Shen, Yun-An A; Hahn, Angela T; McGee, Aaron W; Xu, Xiaomei; Zheng, Binhai; Zhang, Li I; Rowitch, David H; Franklin, Robin J M; Lu, Q Richard; Chan, Jonah R

    2012-01-24

    A requisite component of nervous system development is the achievement of cellular recognition and spatial segregation through competition-based refinement mechanisms. Competition for available axon space by myelinating oligodendrocytes ensures that all relevant CNS axons are myelinated properly. To ascertain the nature of this competition, we generated a transgenic mouse with sparsely labeled oligodendrocytes and establish that individual oligodendrocytes occupying similar axon tracts can greatly vary the number and lengths of their myelin internodes. Here we show that intercellular interactions between competing oligodendroglia influence the number and length of myelin internodes, referred to as myelinogenic potential, and identify the amino-terminal region of Nogo-A, expressed by oligodendroglia, as necessary and sufficient to inhibit this process. Exuberant and expansive myelination/remyelination is detected in the absence of Nogo during development and after demyelination, suggesting that spatial segregation and myelin extent is limited by microenvironmental inhibition. We demonstrate a unique physiological role for Nogo-A in the precise myelination of the developing CNS. Maximizing the myelinogenic potential of oligodendrocytes may offer an effective strategy for repair in future therapies for demyelination.

  13. Oligodendrocyte-microglia cross-talk in the central nervous system.

    PubMed

    Peferoen, Laura; Kipp, Markus; van der Valk, Paul; van Noort, Johannes M; Amor, Sandra

    2014-03-01

    Communication between the immune system and the central nervous system (CNS) is exemplified by cross-talk between glia and neurons shown to be essential for maintaining homeostasis. While microglia are actively modulated by neurons in the healthy brain, little is known about the cross-talk between oligodendrocytes and microglia. Oligodendrocytes, the myelin-forming cells in the CNS, are essential for the propagation of action potentials along axons, and additionally serve to support neurons by producing neurotrophic factors. In demyelinating diseases such as multiple sclerosis, oligodendrocytes are thought to be the victims. Here, we review evidence that oligodendrocytes also have strong immune functions, express a wide variety of innate immune receptors, and produce and respond to chemokines and cytokines that modulate immune responses in the CNS. We also review evidence that during stress events in the brain, oligodendrocytes can trigger a cascade of protective and regenerative responses, in addition to responses that elicit progressive neurodegeneration. Knowledge of the cross-talk between microglia and oligodendrocytes may continue to uncover novel pathways of immune regulation in the brain that could be further exploited to control neuroinflammation and degeneration.

  14. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.

    PubMed Central

    Rice, D; Barone, S

    2000-01-01

    Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 8 Figure 9 Figure 12 Figure 14 Figure 16 Figure 17 PMID:10852851

  15. Axonal retraction and regeneration induced by N,N-diethyldithiocarbamate (DEDTC) in the central nervous system.

    PubMed

    Junyent, Fèlix; Utrera, Juana; Auladell, Carme

    2006-12-01

    Dithiocarbamates (DTCs), such as disulfiram, have been used in aversion therapy for alcoholism even though an inherent toxicity is induced, which is related mainly to peripheral neuropathy and is associated with behavioural and neurological complications. At anatomical and histopathological levels, DTCs affect structural elements in nervous tissue, such as axonal degeneration and alterations in the cytoskeletal proteins of astrocytes. Therefore, given the axonal effects of DTCs and to gain further insight into axonal growth and axonal pathfinding in the central nervous system (CNS), here we established an in vivo experimental model of mouse development. Daily intraperitoneal injections of N,N-diethyldithiocarbamate (DEDTC), the first metabolite of disulfiram, were given from postnatal day 2 (P2) until P15. From P16 until P30, animals were not treated. Treatment induced considerable physiological alterations, such as growth delay, throughout postnatal development. Moreover, by immunohistochemistry techniques, we observed important alterations in the cytoskeletal glial protein at early stages of postnatal development. At later stages (P15), the immunoreactivity pattern detected by an antibody against axonal neurofilaments (anti-NF-H) showed alteration in the axonal distribution pattern followed by drastic axonal loss at P22, data that were corroborated using an anti-MBP (myelin basic protein) antibody. Using an antibody against the beta amyloid precursor protein (APP), we detected axonal injury. Furthermore, given that we observed axonal re-growth in adulthood in the in vivo model presented, we propose that this model would be a good system in which to identify new strategies for inducing regenerative growth in neural diseases in which axonal regeneration is blocked. PMID:17156377

  16. Molecular clocks and the early evolution of metazoan nervous systems.

    PubMed

    Wray, Gregory A

    2015-12-19

    The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation. PMID:26554040

  17. Molecular clocks and the early evolution of metazoan nervous systems.

    PubMed

    Wray, Gregory A

    2015-12-19

    The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation.

  18. The scales and tales of myelination: using zebrafish and mouse to study myelinating glia.

    PubMed

    Ackerman, Sarah D; Monk, Kelly R

    2016-06-15

    Myelin, the lipid-rich sheath that insulates axons to facilitate rapid conduction of action potentials, is an evolutionary innovation of the jawed-vertebrate lineage. Research efforts aimed at understanding the molecular mechanisms governing myelination have primarily focused on rodent models; however, with the advent of the zebrafish model system in the late twentieth century, the use of this genetically tractable, yet simpler vertebrate for studying myelination has steadily increased. In this review, we compare myelinating glial cell biology during development and regeneration in zebrafish and mouse and enumerate the advantages and disadvantages of using each model to study myelination. This article is part of a Special Issue entitled SI: Myelin Evolution.

  19. Quest for the basic plan of nervous system circuitry

    PubMed Central

    Swanson, Larry W.

    2007-01-01

    The basic plan of nervous system organization has been investigated since classical antiquity. The first model centered on pneumas pumped from sensory nerves through the ventricular system and out motor nerves to muscles. It was popular well into the seventeenth century and diverted attention from the organization of brain parenchyma itself. Willis focused on gray matter production and white matter conduction of pneumas in 1664, and by the late nineteenth century a clear cellular model of nervous system organization based on sensory, motor, and association neuron classes transmitting nerve impulses was elaborated by Cajal and his contemporaries. Today, revolutionary advances in experimental pathway tracing methods, molecular genetics, and computer science inspire systems neuroscience. Seven minimal requirements are outlined for knowledge management systems capable of describing, analyzing, and modeling the basic plan of nervous system circuitry in general, and the plan evolved for vertebrates, for mammals, and ultimately for humans in particular. The goal remains a relatively simple, easy to understand model analogous to the one Harvey elaborated in 1628 for circulation in the cardiovascular system. As Cajal wrote in 1909, “To extend our understanding of neural function to the most complex human physiological and psychological activities, it is essential that we first generate a clear and accurate view of the structure of the relevant centers, and of the human brain itself, so that the basic plan—the overview—can be grasped in the blink of an eye.” PMID:17267046

  20. [VARICELLA ZOSTER VIRUS AND DISEASES OF CENTRAL NERVOUS SYSTEM VESSELS].

    PubMed

    Kazanova, A S; Lavrov, V F; Zverev, V V

    2015-01-01

    Systemized data on epidemiology, pathogenesis, clinical manifestation, diagnostics and therapy of VZV-vasculopathy--a disease, occurring due to damage of arteries of the central nervous system by Varicella Zoster virus, are presented in the review. A special attention in the paper is given to the effect of vaccine prophylaxis of chicken pox and herpes zoster on the frequency of development and course of VZV-vasculopathy.

  1. Functional structure and dynamics of the human nervous system

    NASA Technical Reports Server (NTRS)

    Lawrence, J. A.

    1981-01-01

    The status of an effort to define the directions needed to take in extending pilot models is reported. These models are needed to perform closed-loop (man-in-the-loop) feedback flight control system designs and to develop cockpit display requirements. The approach taken is to develop a hypothetical working model of the human nervous system by reviewing the current literature in neurology and psychology and to develop a computer model of this hypothetical working model.

  2. Regulation of sympathetic nervous system function after cardiovascular deconditioning

    NASA Technical Reports Server (NTRS)

    Hasser, E. M.; Moffitt, J. A.

    2001-01-01

    Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently

  3. Introduction to 'Homology and convergence in nervous system evolution'.

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2016-01-01

    The origin of brains and central nervous systems (CNSs) is thought to have occurred before the Palaeozoic era 540 Ma. Yet in the absence of tangible evidence, there has been continued debate whether today's brains and nervous systems derive from one ancestral origin or whether similarities among them are due to convergent evolution. With the advent of molecular developmental genetics and genomics, it has become clear that homology is a concept that applies not only to morphologies, but also to genes, developmental processes, as well as to behaviours. Comparative studies in phyla ranging from annelids and arthropods to mammals are providing evidence that corresponding developmental genetic mechanisms act not only in dorso-ventral and anterior-posterior axis specification but also in segmentation, neurogenesis, axogenesis and eye/photoreceptor cell formation that appear to be conserved throughout the animal kingdom. These data are supported by recent studies which identified Mid-Cambrian fossils with preserved soft body parts that present segmental arrangements in brains typical of modern arthropods, and similarly organized brain centres and circuits across phyla that may reflect genealogical correspondence and control similar behavioural manifestations. Moreover, congruence between genetic and geological fossil records support the notion that by the 'Cambrian explosion' arthropods and chordates shared similarities in brain and nervous system organization. However, these similarities are strikingly absent in several sister- and outgroups of arthropods and chordates which raises several questions, foremost among them: what kind of natural laws and mechanisms underlie the convergent evolution of such similarities? And, vice versa: what are the selection pressures and genetic mechanisms underlying the possible loss or reduction of brains and CNSs in multiple lineages during the course of evolution? These questions were addressed at a Royal Society meeting to discuss

  4. Introduction to 'Homology and convergence in nervous system evolution'.

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2016-01-01

    The origin of brains and central nervous systems (CNSs) is thought to have occurred before the Palaeozoic era 540 Ma. Yet in the absence of tangible evidence, there has been continued debate whether today's brains and nervous systems derive from one ancestral origin or whether similarities among them are due to convergent evolution. With the advent of molecular developmental genetics and genomics, it has become clear that homology is a concept that applies not only to morphologies, but also to genes, developmental processes, as well as to behaviours. Comparative studies in phyla ranging from annelids and arthropods to mammals are providing evidence that corresponding developmental genetic mechanisms act not only in dorso-ventral and anterior-posterior axis specification but also in segmentation, neurogenesis, axogenesis and eye/photoreceptor cell formation that appear to be conserved throughout the animal kingdom. These data are supported by recent studies which identified Mid-Cambrian fossils with preserved soft body parts that present segmental arrangements in brains typical of modern arthropods, and similarly organized brain centres and circuits across phyla that may reflect genealogical correspondence and control similar behavioural manifestations. Moreover, congruence between genetic and geological fossil records support the notion that by the 'Cambrian explosion' arthropods and chordates shared similarities in brain and nervous system organization. However, these similarities are strikingly absent in several sister- and outgroups of arthropods and chordates which raises several questions, foremost among them: what kind of natural laws and mechanisms underlie the convergent evolution of such similarities? And, vice versa: what are the selection pressures and genetic mechanisms underlying the possible loss or reduction of brains and CNSs in multiple lineages during the course of evolution? These questions were addressed at a Royal Society meeting to discuss

  5. [Pleasure, pain and affectivity in the nervous system].

    PubMed

    Houdart, R

    1999-01-01

    Affectivity plays an essential role in human life. It gives life its quality, and is responsible for what human beings have always considered to be main endeavor happiness. Still, looking for its description or organisation, in physiology or neurology, treatises is fruitless; there only one of its components is described pain, with no mention of pleasure. We wish to show, here, first, that pain and pleasure, depend of a same function, of which they are, of sorts, both extremities, and which in nothing but the most primitive function of the nervous system, and secondly, that this function in one of the components of an "affectivity center", which has its organisation in the limbic system. This center, integrating all the informations that arrives to the nervous system, triggers to each of them neuro-vegetative and neuro-hormonal informations that are "felt" by the organism, and thus transforms the information in a subjective feeling.

  6. Involvement of MeCP2 in Regulation of Myelin-Related Gene Expression in Cultured Rat Oligodendrocytes.

    PubMed

    Sharma, Kedarlal; Singh, Juhi; Pillai, Prakash P; Frost, Emma E

    2015-10-01

    Methyl CpG binding protein 2 (MeCP2) is a multifunctional protein which binds to methylated CpG, mutation of which cause a neurodevelopmental disorder, Rett syndrome. MeCP2 can function as both transcriptional activator and repressor of target gene. MeCP2 regulate gene expression in both neuron and glial cells in central nervous system (CNS). Oligodendrocytes, the myelinating cells of CNS, are required for normal functioning of neurons and are regulated by several transcription factors during their differentiation. In current study, we focused on the role of MeCP2 as transcription regulator of myelin genes in cultured rat oligodendrocytes. We have observed expression of MeCP2 at all stages of oligodendrocyte development. MeCP2 knockdown in cultured oligodendrocytes by small interference RNA (siRNA) has shown increase in myelin genes (myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), and myelin-associated oligodendrocyte basic protein (MOBP)), neurotrophin (brain-derived neurotrophic factor (BDNF)), and transcriptional regulator (YY1) transcripts level, which are involved in regulation of oligodendrocyte differentiation and myelination. Further, we also found that protein levels of MBP, PLP, DM-20, and BDNF also significantly upregulated in MeCP2 knockdown oligodendrocytes. Our study suggests that the MeCP2 acts as a negative regulator of myelin protein expression.

  7. Gene profiling in the dynamic regulation of the lifespan of the myelin sheath structure in the optic nerve of rats.

    PubMed

    Xie, Fang; Fu, Han; Zhang, Jiu-Cong; Chen, Xue-Feng; Wang, Xiao-Liang; Chen, Jun

    2014-07-01

    Aging of the nervous system leads to impairments in cognition and motor skills, and is a major risk factor for several neurological disorders. Recently, numerous nerve function deficits that appear with aging have been found to be a consequence of myelin abnormalities; however, the genetic mechanism of the age‑related alterations in the myelin sheath has not yet been fully elucidated. In the present study, the morphology of the myelin sheath in the optic nerve of rats was analyzed at 10 time‑points throughout life. Marked alterations in the myelin sheath were observed in aging and aged optic nerves, and these became progressively more severe with time. To determine the biological processes affected by aging in the myelin sheath, the age‑related profiling of the myelin sheath in rat optic nerves was established using microarray hybridization at 10 time‑points throughout life, between birth and senescence. From the results, 3,826 transcripts associated with the age‑related alterations in the myelin sheath of the optic nerve were identified. It was found that the biological processes most significantly altered by aging were lipid metabolism, the immune response and transmitter transport. This suggests that the downregulation of lipid synthesis genes and the upregulation of immune and neurotransmitter transport genes in aging may be the genetic basis for the age‑related alterations observed in the myelin sheath.

  8. Recurrent demyelination in chronic central nervous system infection produced by Theiler's murine encephalomyelitis virus.

    PubMed

    Dal Canto, M C; Lipton, H L

    1979-08-01

    A morphologic study of demyelination produced by Theiler's encephalomyelitis virus (TMEV) infection in C3H/He mice was performed. Demyelination in this strain of mouse was less intense and had a milder gliomesodermal response than that observed in SJL mice. As early as 80 days after infection numerous remyelinated axons were present in C3H/He mice, and later, extensive remyelination was observed and was mainly by Schwann cells. About one-third of remyelinated plaques showed recurrent demyelinating activity at 200 days. The best evidence of recurrent demyelination was the loss of myelin by abons which had been previously remyelinated by Schwann cells. In addition, acute areas of demyelination were also seen in spinal cords which contained chronic or quiescent plaques. The demonstration of recurrent demyelination in TMEV infection is important for it increases the relevance of this model to multiple sclerosis (MS). In addition TMEV infection of C3H/He mice appears to be an excellent model for further studies of Schwann cell remyelination and recurrent demyelination in the central nervous system (CNS).

  9. HDAC6 is a target for protection and regeneration following injury in the nervous system

    PubMed Central

    Rivieccio, Mark A.; Brochier, Camille; Willis, Dianna E.; Walker, Breset A.; D'Annibale, Melissa A.; McLaughlin, Kathryn; Siddiq, Ambreena; Kozikowski, Alan P.; Jaffrey, Samie R.; Twiss, Jeffery L.; Ratan, Rajiv R.; Langley, Brett

    2009-01-01

    Central nervous system (CNS) trauma can result in tissue disruption, neuronal and axonal degeneration, and neurological dysfunction. The limited spontaneous CNS repair in adulthood and aging is often insufficient to overcome disability. Several investigations have demonstrated that targeting HDAC activity can protect neurons and glia and improve outcomes in CNS injury and disease models. However, the enthusiasm for pan-HDAC inhibition in treating neurological conditions is tempered by their toxicity toward a host of CNS cell types –a biological extension of their anticancer properties. Identification of the HDAC isoform, or isoforms, that specifically mediate the beneficial effects of pan-HDAC inhibition could overcome this concern. Here, we show that pan-HDAC inhibition not only promotes neuronal protection against oxidative stress, a common mediator of injury in many neurological conditions, but also promotes neurite growth on myelin-associated glycoprotein and chondroitin sulfate proteoglycan substrates. Real-time PCR revealed a robust and selective increase in HDAC6 expression due to injury in neurons. Accordingly, we have used pharmacological and genetic approaches to demonstrate that inhibition of HDAC6 can promote survival and regeneration of neurons. Consistent with a cytoplasmic localization, the biological effects of HDAC6 inhibition appear transcription-independent. Notably, we find that selective inhibition of HDAC6 avoids cell death associated with pan-HDAC inhibition. Together, these findings define HDAC6 as a potential nontoxic therapeutic target for ameliorating CNS injury characterized by oxidative stress-induced neurodegeneration and insufficient axonal regeneration. PMID:19884510

  10. [Molecular biological detection of tissues of central nervous system in meat products].

    PubMed

    Lange, Bianca; Alter, Thomas; Froeb, Annekathrin; Lücker, Ernst

    2003-01-01

    In principle, molecular biological methods can be used for the detection of specified risk material (SRM) in meat products. We were able to identify suitable target mRNAs for the marker proteins glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) of tissues of the central nervous system (CNS). The selected primers for GFAP ("GFAP87") and MBP ("MBP51") facilitated the detection of CNS in non-heated and heated standards of emulsion type (and raw) sausages with defined addition of brain by reverse transcription and polymerase chain reaction (RT-PCR). Stability of the mRNA proved to be given over a minimum of 48 hours. First results indicate an even higher stability of the target mRNAs over time and an ample stability against meat technological influences such as storage, temperature, and ripening. RT-PCR with GFAP87 facilitates the detection of CNS of all relevant slaughter animals in meat products. Thus it can be applied in food labeling control. Using RT-PCR and MBP51 as primer we were able to detect selectively the CNS of bovines, ovines and caprines but not CNS of porcines and poultry. Thus we have a second RT-PCR detection procedure for CNS in meat products which, however, yields results equivalent to the legal definition of SRM. The further development of these molecular biological methods would be of considerable importance for routine food control and reduction of human TSE-exposure risk.

  11. The role of the surface on microglia function: implications for central nervous system tissue engineering

    PubMed Central

    Pires, Liliana R.; Rocha, Daniela N.; Ambrosio, Luigi; Pêgo, Ana Paula

    2015-01-01

    In tissue engineering, it is well accepted that a scaffold surface has a decisive impact on cell behaviour. Here we focused on microglia—the resident immune cells of the central nervous system (CNS)—and on their response to poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) fibrous and flat surfaces obtained by electrospinning and solvent cast, respectively. This study aims to provide cues for the design of instructive surfaces that can contribute to the challenging process of CNS regeneration. Cell morphology was evidently affected by the substrate, mirroring the surface main features. Cells cultured on flat substrates presented a round shape, while cells with elongated processes were observed on the electrospun fibres. A higher concentration of the pro-inflammatory cytokine tumour necrosis factor-α was detected in culture media from microglia on fibres. Still, astrogliosis is not exacerbated when astrocytes are cultured in the presence of microglia-conditioned media obtained from cultures in contact with either substrate. Furthermore, a significant percentage of microglia was found to participate in the process of myelin phagocytosis, with the formation of multinucleated giant cells being observed only on films. Altogether, the results presented suggest that microglia in contact with the tested substrates may contribute to the regeneration process, putting forward P(TMC-CL) substrates as supporting matrices for nerve regeneration. PMID:25540243

  12. Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity

    PubMed Central

    Maurer, Michael A.; Rakocevic, Goran; Leung, Carol S.; Quast, Isaak; Lukačišin, Martin; Goebels, Norbert; Münz, Christian; Wardemann, Hedda; Dalakas, Marinos; Lünemann, Jan D.

    2012-01-01

    The B cell–depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti–myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal IgM memory B cell expansions before and after therapy, by persistence of clonal expansions despite efficient peripheral B cell depletion, and by a lack of substantial changes in somatic hypermutation frequencies of IgM memory B cells. We infer from these data that the effectiveness of rituximab therapy depends on efficient depletion of noncirculating B cells and is associated with qualitative immunological changes that indicate reconfiguration of B cell memory through sustained reduction of autoreactive clonal expansions. These findings support the continued development of B cell–depleting therapies for autoimmune diseases. PMID:22426210

  13. Role of inflammation and apoptosis in multiple sclerosis: Comparative analysis between the periphery and the central nervous system.

    PubMed

    Macchi, Beatrice; Marino-Merlo, Francesca; Nocentini, Ugo; Pisani, Valerio; Cuzzocrea, Salvatore; Grelli, Sandro; Mastino, Antonio

    2015-10-15

    Multiple sclerosis (MS) is a complex, multifactorial disease associated with damage to the axonal myelin sheaths and neuronal degeneration. The pathognomonic event in MS is oligodendrocyte loss accompanied by axonal damage, blood-brain barrier leakage, inflammation and infiltration of immune cells. The etiopathogenesis of MS is far from being elucidated. However, increasing evidence suggests that the inflammatory and apoptotic responses, occurring in patients either at the peripheral level or the central nervous system (CNS), can play a role. In this review, we give a comprehensive picture of general aspects of inflammation and apoptosis in MS, with special emphasis on the until now not well highlighted possible links between phenomena relevant to these aspects occurring in either the periphery or in the CNS during MS. PMID:26439966

  14. Gut environment-induced intraepithelial autoreactive CD4+ T cells suppress central nervous system autoimmunity via LAG-3

    PubMed Central

    Kadowaki, Atsushi; Miyake, Sachiko; Saga, Ryoko; Chiba, Asako; Mochizuki, Hideki; Yamamura, Takashi

    2016-01-01

    The gut environment has been found to significantly influence autoimmune diseases such as multiple sclerosis; however, immune cell mechanisms are unclear. Here we show that the gut epithelium of myelin oligodendrocyte glycoprotein(35-55)-specific T-cell receptor transgenic mice contains environmental stimuli-induced intraepithelial lymphocytes (IELs) that inhibit experimental autoimmune encephalomyelitis on transfer. These cells express surface markers phenotypical of ‘induced' IELs, have a TH17-like profile and infiltrate the central nervous system (CNS). They constitutively express Ctla4 and Tgfb1 and markedly upregulate Lag3 expression in the CNS, thereby inhibiting inflammation. We also demonstrate the suppressive capability of CD4+ IELs with alternative antigen specificities, their proliferation in response to gut-derived antigens and contribution of the microbiota and dietary aryl hydrocarbon receptor ligands to their induction. Thus, the gut environment favours the generation of autoreactive CD4+ T cells with unique regulatory functions, potentially important for preventing CNS autoimmunity. PMID:27198196

  15. TDP6, a brain-derived neurotrophic factor-based trkB peptide mimetic, promotes oligodendrocyte myelination.

    PubMed

    Wong, Agnes W; Giuffrida, Lauren; Wood, Rhiannon; Peckham, Haley; Gonsalvez, David; Murray, Simon S; Hughes, Richard A; Xiao, Junhua

    2014-11-01

    Brain-derived neurotrophic factor (BDNF) plays critical roles in the development and maintenance of the central (CNS) and peripheral nervous systems (PNS). BDNF exerts its biological effects via tropomyosin-related kinase B (TrkB) and the p75 neurotrophin receptor (p75NTR). We have recently identified that BDNF promotes CNS myelination via oligodendroglial TrkB receptors. In order to selectively target TrkB to promote CNS myelination, we have used a putative TrkB agonist, a small multicyclic peptide (tricyclic dimeric peptide 6, TDP6) previously described by us that structurally mimics a region of BDNF that binds TrkB. We confirmed that TDP6 acts as a TrkB agonist as it provoked autophosphorylation of TrkB and its downstream signalling effector extracellular related-kinase 1 and 2 (Erk1/2) in primary oligodendrocytes. Using an in vitro myelination assay, we show that TDP6 significantly promotes myelination by oligodendrocytes in vitro, as evidenced by enhanced myelin protein expression and an increased number of myelinated axonal segments. In contrast, a second, structurally distinct BDNF mimetic (cyclo-dPAKKR) that targets p75NTR had no effect upon oligodendrocyte myelination in vitro, despite the fact that cyclo-dPAKKR is a very effective promoter of peripheral (Schwann cell) myelination. The selectivity of TDP6 was further verified by using TrkB-deficient oligodendrocytes, in which TDP6 failed to promote myelination, indicating that the pro-myelinating effect of TDP6 is oligodendroglial TrkB-dependent. Together, our results demonstrate that TDP6 is a novel BDNF mimetic that promotes oligodendrocyte myelination in vitro via targeting TrkB.

  16. The nervous system of Xenacoelomorpha: a genomic perspective.

    PubMed

    Perea-Atienza, Elena; Gavilán, Brenda; Chiodin, Marta; Abril, Josep F; Hoff, Katharina J; Poustka, Albert J; Martinez, Pedro

    2015-02-15

    Xenacoelomorpha is, most probably, a monophyletic group that includes three clades: Acoela, Nemertodermatida and Xenoturbellida. The group still has contentious phylogenetic affinities; though most authors place it as the sister group of the remaining bilaterians, some would include it as a fourth phylum within the Deuterostomia. Over the past few years, our group, along with others, has undertaken a systematic study of the microscopic anatomy of these worms; our main aim is to understand the structure and development of the nervous system. This research plan has been aided by the use of molecular/developmental tools, the most important of which has been the sequencing of the complete genomes and transcriptomes of different members of the three clades. The data obtained has been used to analyse the evolutionary history of gene families and to study their expression patterns during development, in both space and time. A major focus of our research is the origin of 'cephalized' (centralized) nervous systems. How complex brains are assembled from simpler neuronal arrays has been a matter of intense debate for at least 100 years. We are now tackling this issue using Xenacoelomorpha models. These represent an ideal system for this work because the members of the three clades have nervous systems with different degrees of cephalization; from the relatively simple sub-epithelial net of Xenoturbella to the compact brain of acoels. How this process of 'progressive' cephalization is reflected in the genomes or transcriptomes of these three groups of animals is the subject of this paper.

  17. Conserved and divergent expression patterns of the proteolipid protein gene family in the amphibian central nervous system.

    PubMed

    Yoshida, M; Shan, W S; Colman, D R

    1999-07-01

    The recent discovery of a proteolipid protein gene family has revealed that its members are in fact widely distributed and are not exclusively associated with myelination. To date, three different gene products, DMalpha/DM-20/PLP, DMbeta/M6a, and DMgamma/M6b, have been isolated from certain primitive fish species, mouse, and human central nervous system (CNS). We cloned Xenopus laevis orthologues of DMbeta/M6a and DMgamma/M6b and investigated the expression patterns of these gene transcripts as well as that of PLP in developing Xenopus CNS. As is the case in shark and mouse, the mRNA encoding the major myelin integral protein, PLP, is first detected at stage 42/43 in tadpoles and is exclusively found in morphologically recognizable oligodendrocytes throughout the brain, while DMbeta mRNA is solely expressed in young presumptive neurons in the gray matter. There exist two distinct DMgamma mRNAs and, in contrast to these evolutionarily conserved expression patterns, DMgamma mRNAs distribute uniquely within the ventricular zone in young tadpoles (stage 25) through maturity. Furthermore, both DMbeta and DMgamma are expressed in the developing retina, and their distributions are different from one other. In Xenopus CNS, therefore, the expression patterns of three proteolipid proteins, PLP, DMbeta, and DMgamma, are distinct from each other, implying very different roles for their protein products within the cell populations in which they are expressed. PMID:10397631

  18. AAV-Mediated Gene Delivery in a Feline Model of Sandhoff Disease Corrects Lysosomal Storage in the Central Nervous System

    PubMed Central

    Rockwell, Hannah E.; McCurdy, Victoria J.; Eaton, Samuel C.; Wilson, Diane U.; Johnson, Aime K.; Randle, Ashley N.; Bradbury, Allison M.; Gray-Edwards, Heather L.; Baker, Henry J.; Hudson, Judith A.; Cox, Nancy R.; Sena-Esteves, Miguel; Seyfried, Thomas N.

    2015-01-01

    Sandhoff disease (SD) is an autosomal recessive neurodegenerative disease caused by a mutation in the gene for the β-subunit of β-N-acetylhexosaminidase (Hex), resulting in the inability to catabolize ganglioside GM2 within the lysosomes. SD presents with an accumulation of GM2 and its asialo derivative GA2, primarily in the central nervous system. Myelin-enriched glycolipids, cerebrosides and sulfatides, are also decreased in SD corresponding with dysmyelination. At present, no treatment exists for SD. Previous studies have shown the therapeutic benefit of adeno-associated virus (AAV) vector-mediated gene therapy in the treatment of SD in murine and feline models. In this study, we treated presymptomatic SD cats with AAVrh8 vectors expressing feline Hex in the thalamus combined with intracerebroventricular (Thal/ICV) injections. Treated animals showed clearly improved neurologic function and quality of life, manifested in part by prevention or attenuation of whole-body tremors characteristic of untreated animals. Hex activity was significantly elevated, whereas storage of GM2 and GA2 was significantly decreased in tissue samples taken from the cortex, cerebellum, thalamus, and cervical spinal cord. Treatment also increased levels of myelin-enriched cerebrosides and sulfatides in the cortex and thalamus. This study demonstrates the therapeutic potential of AAV for feline SD and suggests a similar potential for human SD patients. PMID:25873306

  19. Fiber optic in vivo imaging in the mammalian nervous system

    PubMed Central

    Mehta, Amit D; Jung, Juergen C; Flusberg, Benjamin A; Schnitzer, Mark J

    2010-01-01

    The compact size, mechanical flexibility, and growing functionality of optical fiber and fiber optic devices are enabling several new modalities for imaging the mammalian nervous system in vivo. Fluorescence microendoscopy is a minimally invasive fiber modality that provides cellular resolution in deep brain areas. Diffuse optical tomography is a non-invasive modality that uses assemblies of fiber optic emitters and detectors on the cranium for volumetric imaging of brain activation. Optical coherence tomography is a sensitive interferometric imaging technique that can be implemented in a variety of fiber based formats and that might allow intrinsic optical detection of brain activity at a high resolution. Miniaturized fiber optic microscopy permits cellular level imaging in the brains of behaving animals. Together, these modalities will enable new uses of imaging in the intact nervous system for both research and clinical applications. PMID:15464896

  20. Neurotropic Enterovirus Infections in the Central Nervous System.

    PubMed

    Huang, Hsing-I; Shih, Shin-Ru

    2015-11-24

    Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS) and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells.

  1. Impact of diabetes on vasculature: focus on nervous system.

    PubMed

    Skljarevski, Vladimir; Veves, Aristidis

    2005-08-01

    Chronic complications of diabetes mellitus represent a major cause of morbidity and mortality among those affected and have an enormous impact on society as a whole. Although these complications manifest as a number of clinically distinct syndromes, the pathology underlying them may be very similar, if not identical. Endothelial dysfunction leading to microcirculatory insufficiency and functional ischemia of tissues are proposed to play a pivotal role in the process of their development and progression. Diabetic complications affecting the nervous system occur not infrequently and may have disastrous consequences. This article reviews diabetic complications affecting central and peripheral nervous systems, focusing on similarities in their underlying microvascular pathology and discussing aspects of potentially successful therapeutic interventions. In addition, the article draws a parallel between microvascular dysfunction observed in persons with overt diabetes and those at risk for it.

  2. Nanoneuromedicines for Degenerative, Inflammatory, and Infectious Nervous System Diseases

    PubMed Central

    Gendelman, Howard E.; Anantharam, Vellareddy; Bronich, Tatiana; Ghaisas, Shivani; Jin, Huajun; Kanthasamy, Anumantha G.; Liu, Xinming; McMillan, JoEllyn; Mosley, R. Lee; Narasimhan, Balaji; Mallapragada, Surya K.

    2015-01-01

    Interest in nanoneuromedicine has grown rapidly due to the immediate need for improved biomarkers and therapies for psychiatric, developmental, traumatic, inflammatory, infectious and degenerative nervous system disorders. These, in whole or in part, are a significant societal burden due to growth in numbers of affected people and in disease severity. Lost productivity of the patient and his or her caregiver, and the emotional and financial burden cannot be overstated. The need for improved health care, treatment and diagnostics are immediate. A means to such an end is nanotechnology. Indeed, recent developments of health-care enabling nanotechnologies and nanomedicines range from biomarker discovery including neuroimaging to therapeutic applications for degenerative, inflammatory and infectious disorders of the nervous system. This review focuses on the current and future potential of the field to positively affect clinical outcomes. PMID:25645958

  3. Neurotropic Enterovirus Infections in the Central Nervous System

    PubMed Central

    Huang, Hsing-I; Shih, Shin-Ru

    2015-01-01

    Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS) and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells. PMID:26610549

  4. Measurement of autophagy flux in the nervous system in vivo

    PubMed Central

    Castillo, K; Valenzuela, V; Matus, S; Nassif, M; Oñate, M; Fuentealba, Y; Encina, G; Irrazabal, T; Parsons, G; Court, F A; Schneider, B L; Armentano, D; Hetz, C

    2013-01-01

    Accurate methods to measure autophagic activity in vivo in neurons are not available, and most of the studies are based on correlative and static measurements of autophagy markers, leading to conflicting interpretations. Autophagy is an essential homeostatic process involved in the degradation of diverse cellular components including organelles and protein aggregates. Autophagy impairment is emerging as a relevant factor driving neurodegeneration in many diseases. Moreover, strategies to modulate autophagy have been shown to provide protection against neurodegeneration. Here we describe a novel and simple strategy to express an autophagy flux reporter in the nervous system of adult animals by the intraventricular delivery of adeno-associated viruses (AAV) into newborn mice. Using this approach we efficiently expressed a monomeric tandem mCherry-GFP-LC3 construct in neurons of the peripheral and central nervous system, allowing the measurement of autophagy activity in pharmacological and disease settings. PMID:24232093

  5. Regulation of cadherin expression in nervous system development

    PubMed Central

    Paulson, Alicia F; Prasad, Maneeshi S; Thuringer, Amanda Henke; Manzerra, Pasquale

    2014-01-01

    This review addresses our current understanding of the regulatory mechanisms for classical cadherin expression during development of the vertebrate nervous system. The complexity of the spatial and temporal expression patterns is linked to morphogenic and functional roles in the developing nervous system. While the regulatory networks controlling cadherin expression are not well understood, it is likely that the multiple signaling pathways active in the development of particular domains also regulate the specific cadherins expressed at that time and location. With the growing understanding of the broader roles of cadherins in cell–cell adhesion and non-adhesion processes, it is important to understand both the upstream regulation of cadherin expression and the downstream effects of specific cadherins within their cellular context. PMID:24526207

  6. Central nervous system histoplasmosis in an immunocompetent pediatric patient.

    PubMed

    Esteban, Ignacio; Minces, Pablo; De Cristofano, Analía M; Negroni, Ricardo

    2016-06-01

    Neurohistoplasmosis is a rare disease, most prevalent in immunosuppressed patients, secondary to disseminated disease with a high mortality rate when diagnosis and treatment are delayed. We report a previously healthy 12 year old girl, from a bat infested region of Tucuman Province, Argentine Republic, who developed meningoencephalitis due to Histoplasma capsulatum. Eighteen months prior to admission the patient started with headaches and intermittent fever. The images of the central nervous system showed meningoencephalitis suggestive of tuberculosis. She received antibiotics and tuberculostatic medications without improvement. Liposomal amphotericin B was administered for six weeks. The patient's clinical status improved remarkably. Finally the culture of cerebral spinal fluid was positive for micelial form of Histoplasma capsulatum. The difficulties surrounding the diagnosis and treatment of neurohistoplasmosis in immunocompetent patients are discussed in this manuscript, as it also intends to alert to the presence of a strain of Histoplasma capsulatum with affinity for the central nervous system.

  7. Enrico Sereni: research on the nervous system of cephalopods.

    PubMed

    De Leo, A

    2008-01-01

    This essay focuses on a paradigmatic moment in neurobiological studies of invertebrates: the research on the nervous system of cephalopods carried out by Enrico Sereni at the Naples Zoological Station between 1925 and 1931. Although he remained unknown on the historiographic scenario, probably due to his early death, he contributed to Italian science of the first half of the twentieth century. In my paper particular attention will be given to Sereni's study on the pigmentary-effector, neurohumoral, and peripheral nervous systems, since they also accounted for the historical foundation of the experimental vein that, through the years, would lead John Zachary Young, Sereni's follower, to the most well-known discovery of the giant nerve fibers.

  8. The role of leptin in central nervous system diseases

    PubMed Central

    Li, Xiao-Mei; Yan, Hai-Jing; Guo, Yi-Shan

    2016-01-01

    Leptin is a peptide hormone produced by adipose tissue and acts in brain centers to control critical physiological functions. Leptin receptors are especially abundant in the hypothalamus and trigger specific neuronal subpopulations, and activate several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway. Although most studies focus on its role in energy intake and expenditure, leptin also plays a critical role in many central nervous system diseases. PMID:26885866

  9. Simultaneous central nervous system complications of C. neoformans infection

    PubMed Central

    González-Duarte, Alejandra; Higera Calleja, Jesus; Mitre, Vicente Gijón; Ramos, Guillermo Garcia

    2009-01-01

    The most common neurological manifestation of Cryptococcus neoformans infection is meningitis. Other less common manifestations include parenchymal central nervous system (CNS) granulomatous disease, hydrocephalus and stroke. C. neoformans is often suspected in immunodepressed patients, but it can be easily overlooked in otherwise healthy patients. This paper provides a detailed clinical description of a patient without immunosupression who developed multiple simultaneous neurological manifestations after the infection with C. neoformans. PMID:21577360

  10. Central nervous system infection caused by Morganella morganii.

    PubMed

    Abdalla, Jehad; Saad, Mustafa; Samnani, Imran; Lee, Prescott; Moorman, Jonathan

    2006-01-01

    Central nervous system (CNS) infection with Morganella morganii is very rare. We describe a 38-year-old female patient with frontal brain abscess caused by M morganii who was unsuccessfully treated. We also review all reported cases of Morganella CNS infections with an emphasis on treatment modalities and outcomes. Aggressive surgical management and appropriate antimicrobial therapy can lead to cure, but the mortality rate for these infections remains high.

  11. Neurotensin: immunohistochemical localization in rat central nervous system.

    PubMed Central

    Uhl, G R; Kuhar, M J; Snyder, S H

    1977-01-01

    Neurotensin immunofluorescence was examined in the rat central nervous system using a well-characterized antiserum directed against this tridecapeptide. Morphological characteristics of the fluorescence indicate its association with neuronal cell bodies and processes in the brain and with cells of the anterior pituitary. Fluorescence is seen in many brain areas, with notable densities in the substantia gelatinosa zones of the spinal cord and trigeminal nucleus, central amygdaloid nucleus, anterior pituitary, median eminence, and preoptic and basal hypothalamic areas. Images PMID:333458

  12. Tissue plasminogen activator in central nervous system physiology and pathology

    PubMed Central

    Melchor, Jerry P.; Strickland, Sidney

    2005-01-01

    Summary Although conventionally associated with fibrin clot degradation, recent work has uncovered new functions for the tissue plasminogen activator (tPA)/plasminogen cascade in central nervous system physiology and pathology. This extracellular proteolytic cascade has been shown to have roles in learning and memory, stress, neuronal degeneration, addiction and Alzheimer’s disease. The current review considers the different ways tPA functions in the brain. PMID:15841309

  13. Eph-ephrin signaling in nervous system development

    PubMed Central

    Cramer, Karina S.; Miko, Ilona J.

    2016-01-01

    Ephrins and Eph receptors enable contact-mediated interactions between cells at every stage of nervous system development. In spite of their broad binding affinities, Eph proteins facilitate specificity in neuronal migration and axon targeting. This review focuses on recent studies that demonstrate how these proteins interact with each other, and with other signaling pathways, to guide specificity in a diverse set of developmental processes. PMID:27092247

  14. Centralization of the deuterostome nervous system predates chordates.

    PubMed

    Nomaksteinsky, Marc; Röttinger, Eric; Dufour, Héloïse D; Chettouh, Zoubida; Lowe, Chris J; Martindale, Mark Q; Brunet, Jean-François

    2009-08-11

    The origin of the chordate central nervous system (CNS) is unknown. One theory is that a CNS was present in the first bilaterian and that it gave rise to both the ventral cord of protostomes and the dorsal cord of deuterostomes. Another theory proposes that the chordate CNS arose by a dramatic process of dorsalization and internalization from a diffuse nerve net coextensive with the skin of the animal, such as enteropneust worms (Hemichordata, Ambulacraria) are supposed to have. We show here that juvenile and adult enteropneust worms in fact have a bona fide CNS, i.e., dense agglomerations of neurons associated with a neuropil, forming two cords, ventral and dorsal. The latter is internalized in the collar as a chordate-like neural tube. Contrary to previous assumptions, the greater part of the adult enteropneust skin is nonneural, although elements of the peripheral nervous system (PNS) are found there. We use molecular markers to show that several neuronal types are anatomically segregated in the CNS and PNS. These neuroanatomical features, whatever their homologies with the chordate CNS, imply that nervous system centralization predates the evolutionary separation of chordate and hemichordate lineages. PMID:19559615

  15. Neuritin, a neurotrophic factor in nervous system physiology.

    PubMed

    Zhou, S; Zhou, J

    2014-04-01

    Neuritin (also known as candidate plasticity gene 15, cpg15) is an activity-induced glycosylphosphatidylinositol- anchored axonal protein and is mainly expressed in the brain. Neuritin mRNA expression is modulated by neurotrophic factors, synaptic activity, hormones, sensory experience, and electroconvulsive seizure therapy. Neuritin has several effects in the nervous system, such as promoting neurite outgrowth, modulating neurite outgrowth during neuronal differentiation, protecting motor neuron axons, promoting dendritic growth, shaping dendritic arbors of target neurons, regulating synaptic plasticity, stabilizing active synapses, promoting synaptic maturation and neuronal migration, promoting the development and maturation of visual cortical neurons, regulating apoptosis of proliferative neurons, and regenerating peripheral nerve and spinal axons. Neuritin is also implicated in cerebral ischemia, depression, and cognitive function in schizophrenia, and it upregulates transient outward K(+) currents in neurons, suggesting that neuritin may be a potential therapeutic target in peripheral and central nervous system diseases. This review focuses on the expression, distribution, and physiological functions of neuritin in the nervous system. PMID:24350851

  16. Gangliosides in the Nervous System: Biosynthesis and Degradation

    NASA Astrophysics Data System (ADS)

    Yu, Robert K.; Ariga, Toshio; Yanagisawa, Makoto; Zeng, Guichao

    Gangliosides, abundant in the nervous system, are known to play crucial modulatory roles in cellular recognition, interaction, adhesion, and signal transduction, particularly during early developmental stages. The expression of gangliosides in the nervous system is developmentally regulated and is closely related to the differentiation state of the cell. Ganglioside biosynthesis occurs in intracellular organelles, from which gangliosides are transported to the plasma membrane. During brain development, the ganglioside composition of the nervous system undergoes remarkable changes and is strictly regulated by the activities of glycosyltransferases, which can occur at different levels of control, including glycosyltransferase gene transcription and posttranslational modification. Genes for glycosyltransferase involved in ganglioside biosynthesis have been cloned and classified into families of glycosyltransferases based on their amino acid sequence similarities. The donor and acceptor substrate specificities are determined by enzymatic analysis of the glycosyltransferase gene products. Cell-type specific regulation of these genes has also been studied. Gangliosides are degraded by lysosomal exoglycosidases. The action of these enzymes occurs frequently in cooperation with activator proteins. Several human diseases are caused by defects of degradative enzymes, resulting in massive accumulation of certain glycolipids, including gangliosides in the lysosomal compartment and other organelles in the brain and visceral organs. Some of the representative lysosomal storage diseases (LSDs) caused by the accumulation of lipids in late endosomes and lysosomes will be discussed.

  17. FoxO Proteins in the Nervous System

    PubMed Central

    Maiese, Kenneth

    2015-01-01

    Acute as well as chronic disorders of the nervous system lead to significant morbidity and mortality for millions of individuals globally. Given the ability to govern stem cell proliferation and differentiated cell survival, mammalian forkhead transcription factors of the forkhead box class O (FoxO) are increasingly being identified as potential targets for disorders of the nervous system, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and auditory neuronal disease. FoxO proteins are present throughout the body, but they are selectively expressed in the nervous system and have diverse biological functions. The forkhead O class transcription factors interface with an array of signal transduction pathways that include protein kinase B (Akt), serum- and glucocorticoid-inducible protein kinase (SgK), IκB kinase (IKK), silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), growth factors, and Wnt signaling that can determine the activity and integrity of FoxO proteins. Ultimately, there exists a complex interplay between FoxO proteins and their signal transduction pathways that can significantly impact programmed cell death pathways of apoptosis and autophagy as well as the development of clinical strategies for the treatment of neurodegenerative disorders. PMID:26171319

  18. Functional roles of neuropeptides in the insect central nervous system

    NASA Astrophysics Data System (ADS)

    Nässel, D. R.

    With the completion of the Drosophila genome sequencing project we can begin to appreciate the extent of the complexity in the components involved in signal transfer and modulation in the nervous system of an animal with reasonably complex behavior. Of all the different classes of signaling substances utilized by the nervous system, the neuropeptides are the most diverse structurally and functionally. Thus peptidergic mechanisms of action in the central nervous system need to be analyzed in the context of the neuronal circuits in which they act and generalized traits cannot be established. By taking advantage of Drosophila molecular genetics and the presence of identifiable neurons, it has been possible to interfere with peptidergic signaling in small populations of central neurons and monitor the consequences on behavior. These studies and experiments on other insects with large identifiable neurons, permitting cellular analysis of signaling mechanisms, have outlined important principles for temporal and spatial action of neuropeptides in outputs of the circadian clock and in orchestrating molting behavior. Considering the large number of neuropeptides available in each insect species and their diverse distribution patterns, it is to be expected that different neuropeptides play roles in most aspects of insect physiology and behavior.

  19. Herpesvirus infections of the central nervous system in immunocompromised patients

    PubMed Central

    Strank, Cornelia

    2012-01-01

    Human herpesviruses may cause infections of the central nervous system during primary infection or following reactivation from a latent state. Especially in immunosuppressed patients the infection can take a life-threatening course, and therefore early diagnosis of herpesvirus-associated neurological diseases should have high priority. Clinical presentation in these patients is usually without typical features, making diagnosis even more challenging. Therefore general broad testing for different herpesviruses in cerebrospinal fluid samples is highly recommended. In addition, determination of the virus DNA level in the cerebrospinal fluid by quantitative assays seems to be of high importance to determine prognosis. Moreover, it might help to differentiate between specific virus-associated disease and unspecific presence of virus in the cerebrospinal fluid, especially in immunocompromised patients. Polymerase chain reaction analysis of cerebrospinal fluid has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesviruses. This review summarizes the role human herpesviruses play in central nervous system infections in immunocompromised patients, with a focus on the clinical manifestation of encephalitis. PMID:22973424

  20. Centralization of the deuterostome nervous system predates chordates.

    PubMed

    Nomaksteinsky, Marc; Röttinger, Eric; Dufour, Héloïse D; Chettouh, Zoubida; Lowe, Chris J; Martindale, Mark Q; Brunet, Jean-François

    2009-08-11

    The origin of the chordate central nervous system (CNS) is unknown. One theory is that a CNS was present in the first bilaterian and that it gave rise to both the ventral cord of protostomes and the dorsal cord of deuterostomes. Another theory proposes that the chordate CNS arose by a dramatic process of dorsalization and internalization from a diffuse nerve net coextensive with the skin of the animal, such as enteropneust worms (Hemichordata, Ambulacraria) are supposed to have. We show here that juvenile and adult enteropneust worms in fact have a bona fide CNS, i.e., dense agglomerations of neurons associated with a neuropil, forming two cords, ventral and dorsal. The latter is internalized in the collar as a chordate-like neural tube. Contrary to previous assumptions, the greater part of the adult enteropneust skin is nonneural, although elements of the peripheral nervous system (PNS) are found there. We use molecular markers to show that several neuronal types are anatomically segregated in the CNS and PNS. These neuroanatomical features, whatever their homologies with the chordate CNS, imply that nervous system centralization predates the evolutionary separation of chordate and hemichordate lineages.

  1. Epigenetics, Nervous System Tumors, and Cancer Stem Cells

    PubMed Central

    Qureshi, Irfan A.; Mehler, Mark F.

    2011-01-01

    Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors. PMID:24212967

  2. What Health-Related Functions Are Regulated by the Nervous System?

    MedlinePlus

    ... Research Planning Scientific Resources Research A-Z Topics Neuroscience Overview Condition Information Parts of the nervous system ... functions does the nervous system control? Why study neuroscience? What are the areas of neuroscience? NICHD Research ...

  3. Proton magnetic resonance spectroscopy of leech muscle and nervous system.

    PubMed

    Petroff, O A; Hogan, E; Johansen, J; Kleinhaus, A L

    1987-01-01

    1. Proton nuclear magnetic resonance spectroscopy (1H NMR) was used to measure the major intracellular metabolites in perchloric acid extracts of the Macrobdella decora muscle and nervous systems and the Oryctolagus cuniculus cerebrum. 2. Acetate, alanine, choline, glutamate, inositol, and lactate were assigned in the spectrum of leech ventral cord, leech muscle, and rabbit cerebrum. 3. Hirudonine and propionate were clearly observed only in the spectrum of leech muscle. 4. Creatine, N-acetyl aspartate, gamma aminobutyric acid, aspartate, and taurine, distinctive components of spectra of the mammalian cerebrum, were not seen in the invertebrate spectra. 5. 1H NMR spectroscopy provides a simple and rapid means of characterizing the major organic metabolites found in leech muscle and nervous tissues.

  4. Effect of myelination on the conduction velocity of optic nerve fibres.

    PubMed

    Tolhurst, D J; Lewis, P R

    1992-04-01

    It was proposed by Rushton in 1951, from theoretical considerations, that myelinated fibres less than 1 micron in diameter would conduct more slowly than unmyelinated fibres of the same size and that myelinated fibres below about 0.7 micron would not conduct at all. The experimental data on which he based his theory are all from the peripheral nervous system where small myelinated fibres are rare, and no experimental verification of Rushton's hypothesis has been attempted. In mammalian optic nerve, nearly all the fibres are myelinated; yet half have diameters below 1 micron, with many below 0.7 micron. The many studies of conduction velocities in the visual system enable a test of Rushton's hypothesis to be made. We have examined the correlations between conduction velocity and fibre diameter from a wide range of published studies of the mammalian visual system. The results of our analysis suggest that the small myelinated fibres of the optic nerve and optic tract conduct action potentials more rapidly than is predicted by Rushton's hypothesis, while the unmyelinated axons within the retina actually conduct more slowly than predicted. There is no reason to believe, in this case, that myelination of a small axon will reduce its conduction velocity.

  5. Fourier domain OCT imaging of American cockroach nervous system

    NASA Astrophysics Data System (ADS)

    Wyszkowska, Joanna; Gorczynska, Iwona; Ruminski, Daniel; Karnowski, Karol; Kowalczyk, Andrzej; Stankiewicz, Maria; Wojtkowski, Maciej

    2012-01-01

    In this pilot study we demonstrate results of structural Fourier domain OCT imaging of the nervous system of Periplaneta americana L. (American cockroach). The purpose of this research is to develop an OCT apparatus enabling structural imaging of insect neural system. Secondary purpose of the presented research is to develop methods of the sample preparation and handling during the OCT imaging experiments. We have performed imaging in the abdominal nerve cord excised from the American cockroach. For this purpose we have developed a Fourier domain / spectral OCT system operating at 820 nm wavelength range.

  6. Structure and stability of internodal myelin in mouse models of hereditary neuropathy.

    PubMed

    Avila, Robin L; Inouye, Hideyo; Baek, Rena C; Yin, Xinghua; Trapp, Bruce D; Feltri, M Laura; Wrabetz, Lawrence; Kirschner, Daniel A

    2005-11-01

    Peripheral neuropathies often result in abnormalities in the structure of internodal myelin, including changes in period and membrane packing, as observed by electron microscopy (EM). Mutations in the gene that encodes the major adhesive structural protein of internodal myelin in the peripheral nervous system of humans and mice--P0 glycoprotein--correlate with these defects. The mechanisms by which P0 mutations interfere with myelin packing and stability are not well understood and cannot be provided by EM studies that give static and qualitative information on fixed material. To gain insights into the pathogenesis of mutant P0, we used x-ray diffraction, which can detect more subtle and dynamic changes in native myelin, to investigate myelin structure in sciatic nerves from murine models of hereditary neuropathies. We used mice with disruption of one or both copies of the P0 gene (models of Charcot-Marie-Tooth-like neuropathy [CMT1B] or Dejerine-Sottas-like neuropathy) and mice with a CMT1B resulting from a transgene encoding P0 with an amino terminal myc-tag. To directly test the structural role of P0, we also examined a mouse that expresses P0 instead of proteolipid protein in central nervous system myelin. To link our findings on unfixed nerves with EM results, we analyzed x-ray patterns from unembedded, aldehyde-fixed nerves and from plastic-embedded nerves. From the x-ray patterns recorded from whole nerves, we assessed the amount of myelin and its quality (i.e. relative thickness and regularity). Among sciatic nerves having different levels of P0, we found that unfixed nerves and, to a lesser extent, fixed but unembedded nerves gave diffraction patterns of sufficient quality to distinguish periods, sometimes differing by a few Angstroms. Certain packing abnormalities were preserved qualitatively by aldehyde fixation, and the relative amount and structural integrity of myelin among nerves could be distinguished. Measurements from the same nerve over time

  7. Myelin basic protein accumulation is impaired in a model of protein deficiency during development.

    PubMed

    Montanha-Rojas, E A; Ferreira, A A; Tenório, F; Barradas, P C

    2005-02-01

    During the development of the central nervous system (CNS) there is a great possibility of permanent effects in consequence of environmental disturbances. Nutritional deficiency is one of the factors that impair the normal CNS formation. In general, the protein deficiency evokes, beyond the damages in the maturation of nervous system, several consequences in body growth, biochemical maturation, motor function and the major cognitive functions. These effects were observed in undernourished children all over the world. Even in a restricted period, the malnutrition status may evoke permanent impairments in feeding behavior and in metabolism. Rats submitted to malnutrition during development, showed a marked decrease in the number of myelinated fibers. This condition may reflect a failure in the beginning of the wrapping of axons by oligodendroglial processes and/or a delay in the myelin synthesis. Myelin basic protein (MBP) is an intracellular oligodendrocyte protein that is directly related to the formation of the myelin sheath. In this study we verified the temporal pattern of MBP expression, by immunohistochemical and immunoblotting analyses, in a model of protein malnutrition induced during the first half of the lactation period. We showed that MBP expression was impaired in our malnutrition model and that some of the effects were maintained in adulthood, with possible consequences in the maturation of myelin sheath.

  8. The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining.

    PubMed

    Guo, Zhi-Bao; Su, Ying-Ying; Wang, Yi-Hui; Wang, Wei; Guo, Da-Zhi

    2016-09-01

    ADAM10 (a disintegrin and metalloprotease 10) is a member of the ADAMs family, which is key in the development of the nervous system, by regulating proliferation, migration, differentiation and survival of various cells, including axonal growth and myelination. Previous studies have investigated the embryonic or postnatal expression of ADAM10, however, detailed information regarding its cellular distribution in the adult stage, to the best of our knowledge, is not available. The present study investigated the expression pattern of the ADAM10 gene in the adult mouse central nervous system (CNS) using an ADAM10 complementary RNA probe for in situ hybridization (ISH). Immunohistochemical staining was used to identify the type of the ISH staining‑positive cells with neuron‑ or astrocyte‑specific antibodies. The results of the current study demonstrated that the ADAM10 gene was predominantly expressed in the neurons of the cerebral cortex, hippocampus, thalamus and cerebellar granular cells in adult mouse CNS. PMID:27431484

  9. The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining

    PubMed Central

    Guo, Zhi-Bao; Su, Ying-Ying; Wang, Yi-Hui; Wang, Wei; Guo, Da-Zhi

    2016-01-01

    ADAM10 (a disintegrin and metalloprotease 10) is a member of the ADAMs family, which is key in the development of the nervous system, by regulating proliferation, migration, differentiation and survival of various cells, including axonal growth and myelination. Previous studies have investigated the embryonic or postnatal expression of ADAM10, however, detailed information regarding its cellular distribution in the adult stage, to the best of our knowledge, is not available. The present study investigated the expression pattern of the ADAM10 gene in the adult mouse central nervous system (CNS) using an ADAM10 complementary RNA probe for in situ hybridization (ISH). Immunohistochemical staining was used to identify the type of the ISH staining-positive cells with neuron- or astrocyte-specific antibodies. The results of the current study demonstrated that the ADAM10 gene was predominantly expressed in the neurons of the cerebral cortex, hippocampus, thalamus and cerebellar granular cells in adult mouse CNS. PMID:27431484

  10. Towards a 'systems'-level understanding of the nervous system and its disorders.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2013-11-01

    It is becoming clear that nervous system development and adult functioning are highly coupled with other physiological systems. Accordingly, neurological and psychiatric disorders are increasingly being associated with a range of systemic comorbidities including, most prominently, impairments in immunological and bioenergetic parameters as well as in the gut microbiome. Here, we discuss various aspects of the dynamic crosstalk between these systems that underlies nervous system development, homeostasis, and plasticity. We believe a better definition of this underappreciated systems physiology will yield important insights into how nervous system diseases with systemic comorbidities arise and potentially identify novel diagnostic and therapeutic strategies.

  11. School reentry for children with acquired central nervous systems injuries.

    PubMed

    Carney, Joan; Porter, Patricia

    2009-01-01

    Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special education is not necessarily a special classroom, but an individualized set of educational needs, determined by a multidisciplinary school team, to promote educational success. The purpose of this article is to inform those pediatricians and pediatric allied health professionals treating children with CNS injury of the systems in place to support successful school reentry and their role in contributing to developing an appropriate educational plan. PMID:19489086

  12. Role of the autonomic nervous system in tumorigenesis and metastasis

    PubMed Central

    Magnon, Claire

    2015-01-01

    Convergence of multiple stromal cell types is required to develop a tumorigenic niche that nurtures the initial development of cancer and its dissemination. Although the immune and vascular systems have been shown to have strong influences on cancer, a growing body of evidence points to a role of the nervous system in promoting cancer development. This review discusses past and current research that shows the intriguing role of autonomic nerves, aided by neurotrophic growth factors and axon cues, in creating a favorable environment for the promotion of tumor formation and metastasis. PMID:27308436

  13. Genomics and the evolutionary origins of nervous system complexity.

    PubMed

    Oakley, Todd H; Rivera, Ajna S

    2008-12-01

    Advances in genomics are leading to increased understanding of the evolution of complexity, especially by beginning to bridge genotype and phenotype. Here, using examples from nervous system evolution, we define general patterns of increased complexity seen across levels of biological organization. We also explore specific evolutionary mechanisms that increase complexity, namely those that increase the number of biological units (parts) in a system. We provide specific neurobiological examples of increased complexity in genes, gene networks, cell types, and tissues/organs. These examples illustrate that while a variety of different mechanisms increase biological complexity, they can be understood in a generalized comparative framework. PMID:19152785

  14. Histophysiology of the vegetative peripheral nervous system of skin.

    PubMed

    Förster, F J; Heine, H; Schaeg, G

    1975-12-31

    Preterminal nerve fibers of the peripheral vegetative nervous system make inmediate contact (neuro-effector-areas) to interstitial cells (I.C.). This connection is characterized through a common glycocalyx with the nerve fiber. The I.C. are specific innervated cells and differ morphologically from Schwann-cells, fibrocytes, and histiocytes. The I.C. are able to come into morphologically different contacts with neighbouring cells by microvilli-like cell protrusions. These neighbouring cells then are able to contact other cells by themselves. The results are interpreted in the sense of electro-mechanical feed-back system of information processing in the vegetative periphery.

  15. Acrolein-mediated injury in nervous system trauma and diseases

    PubMed Central

    Shi, Riyi; Rickett, Todd; Sun, Wenjing

    2012-01-01

    Acrolein, an α,β-unsaturated aldehyde, is a ubiquitous pollutant that is also produced endogenously through lipid peroxidation. This compound is hundreds of times more reactive than other aldehydes such as 4-hydroxynonenal, is produced at much higher concentrations, and persists in solution for much longer than better known free radicals. It has been implicated in disease states known to involve chronic oxidative stress, particularly spinal cord injury and multiple sclerosis. Acrolein may overwhelm the anti-oxidative systems of any cell by depleting glutathione reserves, preventing glutathione regeneration, and inactivating protective enzymes. On the cellular level, acrolein exposure can cause membrane damage, mitochondrial dysfunction, and myelin disruption. Such pathologies can be exacerbated by increased concentrations or duration of exposure, and can occur in normal tissue incubated with injured spinal cord, showing that acrolein can act as a diffusive agent, spreading secondary injury. Several chemical species are capable of binding and inactivating acrolein. Hydralazine in particular can reduce acrolein concentrations and inhibit acrolein-mediated pathologies in vivo. Acrolein scavenging appears to be a novel effective treatment which is primed for rapid translation to the clinic. PMID:21823221

  16. Epizootic vacuolar myelinopathy of the central nervous system of bald eagles (Haliaeetus leucocephalus) and American coots (Fulica americana).

    PubMed

    Thomas, N J; Meteyer, C U; Sileo, L

    1998-11-01

    Unprecedented mortality occurred in bald eagles (Haliaeetus leucocephalus) at DeGray Lake, Arkansas, during the winters of 1994-1995 and 1996-1997. The first eagles were found dead during November, soon after arrival from fall migration, and deaths continued into January during both episodes. In total, 29 eagles died at or near DeGray Lake in the winter of 1994-1995 and 26 died in the winter of 1996-1997; no eagle mortality was noted during the same months of the intervening winter or in the earlier history of the lake. During the mortality events, sick eagles were observed overflying perches or colliding with rock walls. Signs of incoordination and limb paresis were also observed in American coots (Fulica americana) during the episodes of eagle mortality, but mortality in coots was minimal. No consistent abnormalities were seen on gross necropsy of either species. No microscopic findings in organs other than the central nervous system (CNS) could explain the cause of death. By light microscopy, all 26 eagles examined and 62/77 (81%) coots had striking, diffuse, spongy degeneration of the white matter of the CNS. Vacuolation occurred in all myelinated CNS tissue, including the cerebellar folia and medulla oblongata, but was most prominent in the optic tectum. In the spinal cord, vacuoles were concentrated near the gray matter, and occasional swollen axons were seen. Vacuoles were uniformly present in optic nerves but were not evident in the retina or peripheral or autonomic nerves. Cellular inflammatory response to the lesion was distinctly lacking. Vacuoles were 8-50 microns in diameter and occurred individually, in clusters, or in rows. In sections stained by luxol fast blue/periodic acid-Schiff stain, the vacuoles were delimited and transected by myelin strands. Transmission electron microscopy revealed intramyelinic vacuoles formed in the myelin sheaths by splitting of one or more myelin lamellae at the intraperiodic line. This lesion is characteristic of

  17. Epizootic vacuolar myelinopathy of the central nervous system of bald eagles (Haliaeetus leucocephalus) and American coots (Fulica americana)

    USGS Publications Warehouse

    Thomas, N.J.; Meteyer, C.U.; Sileo, L.

    1998-01-01

    Unprecedented mortality occurred in bald eagles (Haliaeetus leucocephalus) at DeGray Lake, Arkansas, during the winters of 1994-1995 and 1996-1997. The first eagles were found dead during November, soon after arrival from fall migration, and deaths continued into January during both episodes. In total, 29 eagles died at or near DeGray Lake in the winter of 1994-1995 and 26 died in the winter of 1996-1997; no eagle mortality was noted during the same months of the intervening winter or in the earlier history of the lake. During the mortality events, sick eagles were observed overflying perches or colliding with rock walls. Signs of incoordination and limb paresis were also observed in American coots (Fulica americana) during the episodes of eagle mortality, but mortality in coots was minimal. No consistent abnormalities were seen on gross necropsy of either species. No microscopic findings in organs other than the central nervous system (CNS) could explain the cause of death. By light microscopy, all 26 eagles examined and 62/77 (81%) coots had striking, diffuse, spongy degeneration of the white matter of the CNS. Vacuolation occurred in all myelinated CNS tissue, including the cerebellar folia and medulla oblongata, but was most prominent in the optic tectum. In the spinal cord, vacuoles were concentrated near the gray matter, and occasional swollen axons were seen. Vacuoles were uniformly present in optic nerves but were not evident in the retina or peripheral or autonomic nerves. Cellular inflammatory response to the lesion was distinctly lacking. Vacuoles were 8-50 microns in diameter and occurred individually, in clusters, or in rows. In sections stained by luxol fast blue/periodic acid-Schiff stain, the vacuoles were delimited and transected by myelin strands. Transmission electron microscopy revealed intramyelinic vacuoles formed in the myelin sheaths by splitting of one or more myelin lamellae at the intraperiodic line. This lesion is characteristic of

  18. Effect of Artificial Gravity: Central Nervous System Neurochemical Studies

    NASA Technical Reports Server (NTRS)

    Fox, Robert A.; D'Amelio, Fernando; Eng, Lawrence F.

    1997-01-01

    The major objective of this project was to assess chemical and morphological modifications occurring in muscle receptors and the central nervous system of animals subjected to altered gravity (2 x Earth gravity produced by centrifugation and simulated micro gravity produced by hindlimb suspension). The underlying hypothesis for the studies was that afferent (sensory) information sent to the central nervous system by muscle receptors would be changed in conditions of altered gravity and that these changes, in turn, would instigate a process of adaptation involving altered chemical activity of neurons and glial cells of the projection areas of the cerebral cortex that are related to inputs from those muscle receptors (e.g., cells in the limb projection areas). The central objective of this research was to expand understanding of how chronic exposure to altered gravity, through effects on the vestibular system, influences neuromuscular systems that control posture and gait. The project used an approach in which molecular changes in the neuromuscular system were related to the development of effective motor control by characterizing neurochemical changes in sensory and motor systems and relating those changes to motor behavior as animals adapted to altered gravity. Thus, the objective was to identify changes in central and peripheral neuromuscular mechanisms that are associated with the re-establishment of motor control which is disrupted by chronic exposure to altered gravity.

  19. Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulates Myelination in Zebrafish.

    PubMed

    Ashikawa, Yoshifumi; Nishimura, Yuhei; Okabe, Shiko; Sasagawa, Shota; Murakami, Soichiro; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Tanaka, Toshio

    2016-01-01

    Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS), and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs). Of the genes differentially expressed in both miconazole- and clobetasol-treated mouse OPCs compared with untreated cells, we identified differentially expressed genes (DEGs) common to both drug treatments. Gene ontology analysis revealed that these DEGs are significantly associated with the sterol biosynthetic pathway, and further bioinformatics analysis suggested that sterol regulatory element binding factors (SREBFs) might be key upstream regulators of the DEGs. In silico screening of a public database for chemicals associated with SREBF activation identified fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, as a drug that increases the expression of known SREBF targets, raising the possibility that fenofibrate may also stimulate myelination. To test this, we performed in vivo imaging of zebrafish expressing a fluorescent reporter protein under the control of the myelin basic protein (mbp) promoter. Treatment of zebrafish with fenofibrate significantly increased expression of the fluorescent reporter compared with untreated zebrafish. This increase was attenuated by co-treatment with fatostatin, a specific inhibitor of SREBFs, confirming that the fenofibrate effect was mediated via SREBFs. Furthermore, incubation of zebrafish

  20. Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulates Myelination in Zebrafish

    PubMed Central

    Ashikawa, Yoshifumi; Nishimura, Yuhei; Okabe, Shiko; Sasagawa, Shota; Murakami, Soichiro; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Tanaka, Toshio

    2016-01-01

    Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS), and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs). Of the genes differentially expressed in both miconazole- and clobetasol-treated mouse OPCs compared with untreated cells, we identified differentially expressed genes (DEGs) common to both drug treatments. Gene ontology analysis revealed that these DEGs are significantly associated with the sterol biosynthetic pathway, and further bioinformatics analysis suggested that sterol regulatory element binding factors (SREBFs) might be key upstream regulators of the DEGs. In silico screening of a public database for chemicals associated with SREBF activation identified fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, as a drug that increases the expression of known SREBF targets, raising the possibility that fenofibrate may also stimulate myelination. To test this, we performed in vivo imaging of zebrafish expressing a fluorescent reporter protein under the control of the myelin basic protein (mbp) promoter. Treatment of zebrafish with fenofibrate significantly increased expression of the fluorescent reporter compared with untreated zebrafish. This increase was attenuated by co-treatment with fatostatin, a specific inhibitor of SREBFs, confirming that the fenofibrate effect was mediated via SREBFs. Furthermore, incubation of zebrafish

  1. Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulates Myelination in Zebrafish.

    PubMed

    Ashikawa, Yoshifumi; Nishimura, Yuhei; Okabe, Shiko; Sasagawa, Shota; Murakami, Soichiro; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Tanaka, Toshio

    2016-01-01

    Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS), and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs). Of the genes differentially expressed in both miconazole- and clobetasol-treated mouse OPCs compared with untreated cells, we identified differentially expressed genes (DEGs) common to both drug treatments. Gene ontology analysis revealed that these DEGs are significantly associated with the sterol biosynthetic pathway, and further bioinformatics analysis suggested that sterol regulatory element binding factors (SREBFs) might be key upstream regulators of the DEGs. In silico screening of a public database for chemicals associated with SREBF activation identified fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, as a drug that increases the expression of known SREBF targets, raising the possibility that fenofibrate may also stimulate myelination. To test this, we performed in vivo imaging of zebrafish expressing a fluorescent reporter protein under the control of the myelin basic protein (mbp) promoter. Treatment of zebrafish with fenofibrate significantly increased expression of the fluorescent reporter compared with untreated zebrafish. This increase was attenuated by co-treatment with fatostatin, a specific inhibitor of SREBFs, confirming that the fenofibrate effect was mediated via SREBFs. Furthermore, incubation of zebrafish

  2. Measuring Cardiac Autonomic Nervous System (ANS) Activity in Children

    PubMed Central

    van Eijsden, Manon; Gemke, Reinoud J. B. J.; Vrijkotte, Tanja G. M.; de Geus, Eco J.

    2013-01-01

    The autonomic nervous system (ANS) controls mainly automatic bodily functions that are engaged in homeostasis, like heart rate, digestion, respiratory rate, salivation, perspiration and renal function. The ANS has two main branches: the sympathetic nervous system, preparing the human body for action in times of danger and stress, and the parasympathetic nervous system, which regulates the resting state of the body. ANS activity can be measured invasively, for instance by radiotracer techniques or microelectrode recording from superficial nerves, or it can be measured non-invasively by using changes in an organ's response as a proxy for changes in ANS activity, for instance of the sweat glands or the heart. Invasive measurements have the highest validity but are very poorly feasible in large scale samples where non-invasive measures are the preferred approach. Autonomic effects on the heart can be reliably quantified by the recording of the electrocardiogram (ECG) in combination with the impedance cardiogram (ICG), which reflects the changes in thorax impedance in response to respiration and the ejection of blood from the ventricle into the aorta. From the respiration and ECG signals, respiratory sinus arrhythmia can be extracted as a measure of cardiac parasympathetic control. From the ECG and the left ventricular ejection signals, the preejection period can be extracted as a measure of cardiac sympathetic control. ECG and ICG recording is mostly done in laboratory settings. However, having the subjects report to a laboratory greatly reduces ecological validity, is not always doable in large scale epidemiological studies, and can be intimidating for young children. An ambulatory device for ECG and ICG simultaneously resolves these three problems. Here, we present a study design for a minimally invasive and rapid assessment of cardiac autonomic control in children, using a validated ambulatory device 1-5, the VU University Ambulatory Monitoring System (VU

  3. EGFR Activation Mediates Inhibition of Axon Regeneration by Myelin and Chondroitin Sulfate Proteoglycans

    NASA Astrophysics Data System (ADS)

    Koprivica, Vuk; Cho, Kin-Sang; Park, Jong Bae; Yiu, Glenn; Atwal, Jasvinder; Gore, Bryan; Kim, Jieun A.; Lin, Estelle; Tessier-Lavigne, Marc; Chen, Dong Feng; He, Zhigang

    2005-10-01

    Inhibitory molecules associated with myelin and the glial scar limit axon regeneration in the adult central nervous system (CNS), but the underlying signaling mechanisms of regeneration inhibition are not fully understood. Here, we show that suppressing the kinase function of the epidermal growth factor receptor (EGFR) blocks the activities of both myelin inhibitors and chondroitin sulfate proteoglycans in inhibiting neurite outgrowth. In addition, regeneration inhibitors trigger the phosphorylation of EGFR in a calcium-dependent manner. Local administration of EGFR inhibitors promotes significant regeneration of injured optic nerve fibers, pointing to a promising therapeutic avenue for enhancing axon regeneration after CNS injury.

  4. Myelin basic protein synthesis is regulated by small non-coding RNA 715.

    PubMed

    Bauer, Nina M; Moos, Christina; van Horssen, Jack; Witte, Maarten; van der Valk, Paul; Altenhein, Benjamin; Luhmann, Heiko J; White, Robin

    2012-09-01

    Oligodendroglial Myelin Basic Protein (MBP) synthesis is essential for myelin formation in the central nervous system. During oligodendrocyte differentiation, MBP mRNA is kept in a translationally silenced state while intracellularly transported, until neuron-derived signals initiate localized MBP translation. Here we identify the small non-coding RNA 715 (sncRNA715) as an inhibitor of MBP translation. SncRNA715 localizes to cytoplasmic granular structures and associates with MBP mRNA transport granule components. We also detect increased levels of sncRNA715 in demyelinated chronic human multiple sclerosis lesions, which contain MBP mRNA but lack MBP protein.

  5. The Adverse Effects of Air Pollution on the Nervous System

    PubMed Central

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  6. N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content

    SciTech Connect

    Viquez, Olga M.; Lai, Barry; Ahn, Jae Hee; Does, Mark D.; Valentine, Holly L.; Valentine, William M.

    2009-08-15

    dithiocarbamate-mediated inhibition of proteasome function and inhibition of cuproenzyme activity to neurotoxicity, and also to assess the potential of dithiocarbamates to promote oxidative stress and injury within the central nervous system. These evaluations were performed using an established model for dithiocarbamate-mediated demyelination in the rat utilizing sciatic nerve, spinal cord and brain samples obtained from rats exposed to N,N-diethyldithiocarbamate (DEDC) by intra-abdominal pumps for periods of 2, 4, and 8 weeks and from non exposed controls. The data supported the ability of DEDC to increase copper within myelin and to enhance oxidative stress prior to structural changes detectable by MET{sub 2}. Evidence was also obtained that the excess copper produced by DEDC in the central nervous system is redox active and promotes oxidative injury.

  7. Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous system.

    PubMed

    Zonta, Barbara; Tait, Steven; Melrose, Shona; Anderson, Heather; Harroch, Sheila; Higginson, Jennifer; Sherman, Diane L; Brophy, Peter J

    2008-06-30

    Rapid nerve impulse conduction in myelinated axons requires the concentration of voltage-gated sodium channels at nodes of Ranvier. Myelin-forming oligodendrocytes in the central nervous system (CNS) induce the clustering of sodium channels into nodal complexes flanked by paranodal axoglial junctions. However, the molecular mechanisms for nodal complex assembly in the CNS are unknown. Two isoforms of Neurofascin, neuronal Nfasc186 and glial Nfasc155, are components of the nodal and paranodal complexes, respectively. Neurofascin-null mice have disrupted nodal and paranodal complexes. We show that transgenic Nfasc186 can rescue the nodal complex when expressed in Nfasc(-/-) mice in the absence of the Nfasc155-Caspr-Contactin adhesion complex. Reconstitution of the axoglial adhesion complex by expressing transgenic Nfasc155 in oligodendrocytes also rescues the nodal complex independently of Nfasc186. Furthermore, the Nfasc155 adhesion complex has an additional function in promoting the migration of myelinating processes along CNS axons. We propose that glial and neuronal Neurofascins have distinct functions in the assembly of the CNS node of Ranvier. PMID:18573915

  8. Sox4 participates in the modulation of Schwann cell myelination.

    PubMed

    Bartesaghi, Luca; Arnaud Gouttenoire, Estelle; Prunotto, Andrea; Médard, Jean-Jacques; Bergmann, Sven; Chrast, Roman

    2015-07-01

    In order to identify new regulators of Schwann cell myelination potentially playing a role in peripheral nervous system (PNS) pathologies, we analysed gene expression profiling data from three mouse models of demyelinating neuropathies and from the developing PNS. This analysis revealed that Sox4, which encodes a member of the Sry-related high-mobility group box protein family, was consistently upregulated in all three analysed models of neuropathy. Moreover, Sox4 showed a peak in its expression during development that corresponded with the onset of myelination. To gain further insights into the role of Sox4 in PNS development, we generated a transgenic mouse that specifically overexpresses Sox4 in Schwann cells. Sox4 overexpression led to a temporary delay in PNS myelination without affecting axonal sorting. Importantly, we observed that, whereas Sox4 mRNA could be efficiently overexpressed, Sox4 protein expression in Schwann cells was strictly regulated. Finally, our data showed that enforced expression of Sox4 in the mouse model for Charcot-Marie-Tooth 4C aggravated its neuropathic phenotype. Together, these observations reveal that Sox4 contributes to the regulation of Schwann cell myelination, and also indicates its involvement in the pathophysiology of peripheral neuropathies.

  9. Applications of Nanotechnology to the Central Nervous System

    NASA Astrophysics Data System (ADS)

    Blumling, James P., II

    Nanotechnology and nanomaterials, in general, have become prominent areas of academic research. The ability to engineer at the nano scale is critical to the advancement of the physical and medical sciences. In the realm of physical sciences, the applications are clear: smaller circuitry, more powerful computers, higher resolution intruments. However, the potential impact in the fields of biology and medicine are perhaps even grander. The implementation of novel nanodevices is of paramount importance to the advancement of drug delivery, molecular detection, and cellular manipulation. The work presented in this thesis focuses on the development of nanotechnology for applications in neuroscience. The nervous system provides unique challenges and opportunities for nanoscale research. This thesis discusses some background in nanotechnological applications to the central nervous system and details: (1) The development of a novel calcium nanosenser for use in neurons and astrocytes. We implemented the calcium responsive component of Dr. Roger Tsien's Cameleon sensor, a calmodulin-M13 fusion, in the first quantum dot-based calcium sensor. (2) The exploration of cell-penetrating peptides as a delivery mechanism for nanoparticles to cells of the nervous system. We investigated the application of polyarginine sequences to rat primary cortical astrocytes in order to assess their efficacy in a terminally differentiated neural cell line. (3) The development of a cheap, biocompatible alternative to quantum dots for nanosensor and imaging applications. We utilized a positively charged co-matrix to promote the encapsulation of free sulforhodamine B in silica nanoparticles, a departure from conventional reactive dye coupling to silica matrices. While other methods have been invoked to trap dye not directly coupled to silica, they rely on positively charged dyes that typically have a low quantum yield and are not extensively tested biologically, or they implement reactive dyes bound

  10. Characterization of dendritic spines in the Drosophila central nervous system.

    PubMed

    Leiss, Florian; Koper, Ewa; Hein, Irina; Fouquet, Wernher; Lindner, Jana; Sigrist, Stephan; Tavosanis, Gaia

    2009-03-01

    Dendritic spines are a characteristic feature of a number of neurons in the vertebrate nervous system and have been implicated in processes that include learning and memory. In spite of this, there has been no comprehensive analysis of the presence of spines in a classical genetic system, such as Drosophila, so far. Here, we demonstrate that a subset of processes along the dendrites of visual system interneurons in the adult fly central nervous system, called LPTCs, closely resemble vertebrate spines, based on a number of criteria. First, the morphology, size, and density of these processes are very similar to those of vertebrate spines. Second, they are enriched in actin and devoid of tubulin. Third, they are sites of synaptic connections based on confocal and electron microscopy. Importantly, they represent a preferential site of localization of an acetylcholine receptor subunit, suggesting that they are sites of excitatory synaptic input. Finally, their number is modulated by the level of the small GTPase dRac1. Our results provide a basis to dissect the genetics of dendritic spine formation and maintenance and the functional role of spines.

  11. Attack of the nervous system by Clostridium perfringens Epsilon toxin: from disease to mode of action on neural cells.

    PubMed

    Wioland, Laetitia; Dupont, Jean-Luc; Bossu, Jean-Louis; Popoff, Michel R; Poulain, Bernard

    2013-12-01

    Epsilon toxin (ET), produced by Clostridium perfringens types B and D, ranks among the four most potent poisonous substances known so far. ET-intoxication is responsible for enterotoxaemia in animals, mainly sheep and goats. This disease comprises several manifestations indicating the attack of the nervous system. This review aims to summarize the effects of ET on central nervous system. ET binds to endothelial cells of brain capillary vessels before passing through the blood-brain barrier. Therefore, it induces perivascular oedema and accumulates into brain. ET binding to different brain structures and to different component in the brain indicates regional susceptibility to the toxin. Histological examination has revealed nerve tissue and cellular lesions, which may be directly or indirectly caused by ET. The naturally occurring disease caused by ET-intoxication can be reproduced experimentally in rodents. In mice and rats, ET recognizes receptor at the surface of different neural cell types, including certain neurons (e.g. the granule cells in cerebellum) as well as oligodendrocytes, which are the glial cells responsible for the axons myelination. Moreover, ET induces release of glutamate and other transmitters, leading to firing of neural network. The precise mode of action of ET on neural cells remains to be determined.

  12. Structure and expression of a novel compact myelin protein – Small VCP-interacting protein (SVIP)

    SciTech Connect

    Wu, Jiawen; Peng, Dungeng; Voehler, Markus; Sanders, Charles R.; Li, Jun

    2013-10-11

    Highlights: •SVIP (small p97/VCP-interacting protein) co-localizes with myelin basic protein (MBP) in compact myelin. •We determined that SVIP is an intrinsically disordered protein (IDP). •The helical content of SVIP increases dramatically during its interaction with negatively charged lipid membrane. •This study provides structural insight into interactions between SVIP and myelin membranes. -- Abstract: SVIP (small p97/VCP-interacting protein) was initially identified as one of many cofactors regulating the valosin containing protein (VCP), an AAA+ ATPase involved in endoplasmic-reticulum-associated protein degradation (ERAD). Our previous study showed that SVIP is expressed exclusively in the nervous system. In the present study, SVIP and VCP were seen to be co-localized in neuronal cell bodies. Interestingly, we also observed that SVIP co-localizes with myelin basic protein (MBP) in compact myelin, where VCP was absent. Furthermore, using nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopic measurements, we determined that SVIP is an intrinsically disordered protein (IDP). However, upon binding to the surface of membranes containing a net negative charge, the helical content of SVIP increases dramatically. These findings provide structural insight into interactions between SVIP and myelin membranes.

  13. Polarization-dependent responses of fluorescent indicators partitioned into myelinated axons

    NASA Astrophysics Data System (ADS)

    Micu, Ileana; Brideau, Craig; Stys, Peter K.

    2012-02-01

    Myelination, i.e. the wrapping of axons in multiple layers of lipid-rich membrane, is a unique phenomenon in the nervous systems of both vertebrates and invertebrates, that greatly increases the speed and efficiency of signal transmission. In turn, disruption of axo-myelinic integrity underlies disability in numerous clinical disorders. The dependence of myelin physiology on nanometric organization of its lamellae makes it difficult to accurately study this structure in the living state. We expected that fluorescent probes might become highly oriented when partitioned into the myelin sheath, and in turn, this anisotropy could be interrogated by controlling the polarization state of the exciting laser field used for 2-photon excited fluorescence (TPEF). Live ex vivo myelinated rodent axons were labeled with a series of lipohilic and hydrophilic fluorescenct probes, and TPEF images acquired while laser polarization was varied at the sample over a broad range of ellipticities and orientations of the major angle [see Brideau, Micu & Stys, abstract this meeting]. We found that most probes exhibited strong dependence on both the major angle of polarization, and perhaps more surprisingly, on ellipticity as well. Lipophilic vs. hydrophilic probes exhibited distinctly different behavior. We propose that polarization-dependent TPEF microscopy represents a powerful tool for probing the nanostructural architecture of both myelin and axonal cytoskeleton in a domain far below the resolution limit of visible light microscopy. By selecting probes with different sizes and physicochemical properties, distinct aspects of cellular nanoarchitecture can be accurately interrogated in real-time in living tissue.

  14. Tricarboxylic acid cycle-sustained oxidative phosphorylation in isolated myelin vesicles.

    PubMed

    Ravera, Silvia; Bartolucci, Martina; Calzia, Daniela; Aluigi, Maria Grazia; Ramoino, Paola; Morelli, Alessandro; Panfoli, Isabella

    2013-11-01

    The Central Nervous System (CNS) function was shown to be fueled exclusively by oxidative phosphorylation (OXPHOS). This is in line with the sensitivity of brain to hypoxia, but less with the scarcity of the mitochondria in CNS. Consistently with the ectopic expression of FoF1-ATP synthase and the electron transfer chain in myelin, we have reported data demonstrating that isolated myelin vesicles (IMV) conduct OXPHOS. It may suggest that myelin sheath could be a site for the whole aerobic degradation of glucose. In this paper, we assayed the functionality of glycolysis and of TCA cycle enzymes in IMV purified from bovine forebrain. We found the presence and activity of all of the glycolytic and TCA cycle enzymes, comparable to those in mitochondria-enriched fractions, in the same experimental conditions. IMV also contain consistent carbonic anhydrase activity. These data suggest that myelin may be a contributor in energy supply for the axon, performing an extra-mitochondrial aerobic OXPHOS. The vision of myelin as the site of aerobic metabolism may shed a new light on many demyelinating pathologies, that cause an a yet unresolved axonal degeneration and whose clinical onset coincides with myelin development completion.

  15. [Metastasis tumors of the central nervous system: molecular biology].

    PubMed

    Bello, M Josefa; González-Gómez, P; Rey, J A

    2004-12-01

    Metastases in the nervous system represent an important and growing problem in the clinical practice, being the cause of a great mortality in the developed countries. This article reviews the few data available on the molecular mechanisms involved in the pathogenesis of these tumours, leading to oncogene activation, inactivation of tumour suppressor genes, not only by the classical mechanisms, but also by the tumour cell epigenetic balance alteration. We conclude that all this knowledge will lead in the future to a better diagnosis, treatment and clinic evolution of these patients.

  16. Do dental infections really cause central nervous system infections?

    PubMed

    Lazow, Stewart K; Izzo, Steven R; Vazquez, David

    2011-11-01

    In the post-World War I antibiotic era, the prevalence of central nervous system (CNS) infections is estimated to be 1 per 100,000 population. The literature is replete with anecdotal case reports of CNS infections of apparent dental etiology. Conversely, it is widely cited that the incidence of CNS infection of dental etiology is only in the range of 1% to 2%. We seek to answer the question if dental infections really cause CNS infections. In this article, we focus on septic cavernous sinus thrombosis and brain abscess and if it is a diagnosis of exclusion or evidence-based.

  17. Imagery and the autonomic nervous system: some methodological issues.

    PubMed

    Di Giusto, E L; Bond, N W

    1979-04-01

    The present paper is concerned with the role played by image content in the mediation of autonomic nervous system (ANS) arousal. The minimum methodological requirements of such studies are described including controls for imaging, image content, and expectancy effects. Studies meeting these requirements are then reviewed. It is concluded that image content can be a significant modifier of ANS arousal and that this property is not restricted to images containing affective, e.g., phobic, content. These conclusions have relevance to research into techniques such as biofeedback, Transcendental Meditation, and progressive relaxation, where imagery many have a profound influence but where it has received little direct empirical attentiol.

  18. Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair

    PubMed Central

    Siebert, Justin R.; Conta Steencken, Amanda; Osterhout, Donna J.

    2014-01-01

    Chondroitin sulfate proteoglycans (CSPGs) are widely expressed in the normal central nervous system, serving as guidance cues during development and modulating synaptic connections in the adult. With injury or disease, an increase in CSPG expression is commonly observed close to lesioned areas. However, these CSPG deposits form a substantial barrier to regeneration and are largely responsible for the inability to repair damage in the brain and spinal cord. This review discusses the role of CSPGs as inhibitors, the role of inflammation in stimulating CSPG expression near site of injury, and therapeutic strategies for overcoming the inhibitory effects of CSPGs and creating an environment conducive to nerve regeneration. PMID:25309928

  19. West Nile Virus Infection in the Central Nervous System

    PubMed Central

    Winkelmann, Evandro R.; Luo, Huanle; Wang, Tian

    2016-01-01

    West Nile virus (WNV), a neurotropic single-stranded flavivirus has been the leading cause of arboviral encephalitis worldwide.  Up to 50% of WNV convalescent patients in the United States were reported to have long-term neurological sequelae.  Neither antiviral drugs nor vaccines are available for humans.  Animal models have been used to investigate WNV pathogenesis and host immune response in humans.  In this review, we will discuss recent findings from studies in animal models of WNV infection, and provide new insights on WNV pathogenesis and WNV-induced host immunity in the central nervous system. PMID:26918172

  20. Nonviral Gene Therapy of the Nervous System: Electroporation.

    PubMed

    Ding, Xue-Feng; Fan, Ming

    2016-01-01

    Electroporation has been widely used to efficiently transfer foreign genes into the mammalian central nervous system (CNS), and thus plays an important role in gene therapeutic studies on some brain disorders. A lot of work concerning electroporation is focused on gene transfer into rodent brains. This technique involves an injection of nucleic acids into the brain ventricle or specific area and then applying appropriate electrical field to the injected area. Here, we briefly introduced the advantages and the basic procedures of gene transfer into the rodent brain using electroporation. Better understanding of electroporation in rodent brain may further facilitate gene therapeutic studies on brain disorders.

  1. Neuroactive steroids and the peripheral nervous system: An update.

    PubMed

    Giatti, Silvia; Romano, Simone; Pesaresi, Marzia; Cermenati, Gaia; Mitro, Nico; Caruso, Donatella; Tetel, Marc J; Garcia-Segura, Luis Miguel; Melcangi, Roberto C

    2015-11-01

    In the present review we summarize observations to date supporting the concept that neuroactive steroids are synthesized in the peripheral nervous system, regulate the physiology of peripheral nerves and exert notable neuroprotective actions. Indeed, neuroactive steroids have been recently proposed as therapies for different types of peripheral neuropathy, like for instance those occurring during aging, chemotherapy, physical injury and diabetes. Moreover, pharmacological tools able to increase the synthesis of neuroactive steroids might represent new interesting therapeutic strategy to be applied in case of peripheral neuropathy.

  2. Area 51: How do Acanthamoeba invade the central nervous system?

    PubMed

    Siddiqui, Ruqaiyyah; Emes, Richard; Elsheikha, Hany; Khan, Naveed Ahmed

    2011-05-01

    Acanthamoeba granulomatous encephalitis generally develops as a result of haematogenous spread, but it is unclear how circulating amoebae enter the central nervous system (CNS) and cause inflammation. At present, the mechanisms which Acanthamoeba use to invade this incredibly well-protected area of the CNS and produce infection are not well understood. In this paper, we propose two key virulence factors: mannose-binding protein and extracellular serine proteases as key players in Acanthamoeba traversal of the blood-brain barrier leading to neuronal injury. Both molecules should provide excellent opportunities as potential targets in the rational development of therapeutic interventions against Acanthamoeba encephalitis.

  3. Herpesvirus Transport to the Nervous System and Back Again

    PubMed Central

    Smith, Gregory

    2013-01-01

    Herpes simplex virus, varicella zoster virus, and pseudorabies virus are neurotropic pathogens of the Alphaherpesvirinae subfamily of the Herpesviridae. These viruses efficiently invade the peripheral nervous system and establish lifelong latency in neurons resident in peripheral ganglia. Primary and recurrent infections cycle virus particles between neurons and the peripheral tissues they innervate. This remarkable cycle of infection is the topic of this review. In addition, some of the distinguishing hallmarks of the infections caused by these viruses are evaluated in terms of their underlying similarities. PMID:22726218

  4. Imaging of cancer therapy-induced central nervous system toxicity.

    PubMed

    Dietrich, Jörg; Klein, Joshua P

    2014-02-01

    Cancer therapy, including radiation and chemotherapy, can be associated with harmful effects to the central nervous system. Recognition of classical neurotoxic syndromes is critical to appropriately guide and optimize patient management. As a result of cancer therapy-induced toxicity, patients may present with acute, subacute, and chronic neurologic symptoms that can be misinterpreted as tumor recurrence, infection, or paraneoplastic syndromes. In this review the advantages and limitations of various neuroimaging modalities such as computed tomography, magnetic resonance imaging, and positron emission tomography, frequently used in patients with cancer who present with diverse neurotoxic syndromes, are highlighted. PMID:24287388

  5. The effect of octopamine on the locust stomatogastric nervous system.

    PubMed

    Rand, David; Knebel, Daniel; Ayali, Amir

    2012-01-01

    Octopamine (OA) is a prominent neuromodulator of invertebrate nervous systems, influencing multiple physiological processes. Among its many roles in insects are the initiation and maintenance of various rhythmic behaviors. Here, the neuromodulatory effects of OA on the components of the locust stomatogastric nervous system were studied, and one putative source of OA modulation of the system was identified. Bath application of OA was found to abolish the endogenous rhythmic output of the fully isolated frontal ganglion (FG), while stimulating motor activity of the fully isolated hypocerebral ganglion (HG). OA also induced rhythmic movements in a foregut preparation with intact HG innervation. Complex dose-dependent effects of OA on interconnected FG-HG preparations were seen: 10(-5) M OA accelerated the rhythmic activity of both the HG and FG in a synchronized manner, while 10(-4) M OA decreased both rhythms. Intracellular stimulation of an identified octopaminergic dorsal unpaired median neuron in the subesophageal ganglion was found to exert a similar effect on the FG motor output as that of OA application. Our findings suggest a mechanism of regulation of insect gut patterns and feeding-related behavior during stress and times of high energy demand. PMID:22934040

  6. Ion Channels as Drug Targets in Central Nervous System Disorders

    PubMed Central

    Waszkielewicz, A.M; Gunia, A; Szkaradek, N; Słoczyńska, K; Krupińska, S; Marona, H

    2013-01-01

    Ion channel targeted drugs have always been related with either the central nervous system (CNS), the peripheral nervous system, or the cardiovascular system. Within the CNS, basic indications of drugs are: sleep disorders, anxiety, epilepsy, pain, etc. However, traditional channel blockers have multiple adverse events, mainly due to low specificity of mechanism of action. Lately, novel ion channel subtypes have been discovered, which gives premises to drug discovery process led towards specific channel subtypes. An example is Na+ channels, whose subtypes 1.3 and 1.7-1.9 are responsible for pain, and 1.1 and 1.2 – for epilepsy. Moreover, new drug candidates have been recognized. This review is focusing on ion channels subtypes, which play a significant role in current drug discovery and development process. The knowledge on channel subtypes has developed rapidly, giving new nomenclatures of ion channels. For example, Ca2+ channels are not any more divided to T, L, N, P/Q, and R, but they are described as Cav1.1-Cav3.3, with even newer nomenclature α1A-α1I and α1S. Moreover, new channels such as P2X1-P2X7, as well as TRPA1-TRPV1 have been discovered, giving premises for new types of analgesic drugs. PMID:23409712

  7. Gut commensalism, cytokines, and central nervous system demyelination.

    PubMed

    Telesford, Kiel; Ochoa-Repáraz, Javier; Kasper, Lloyd H

    2014-08-01

    There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination.

  8. Gut commensalism, cytokines, and central nervous system demyelination.

    PubMed

    Telesford, Kiel; Ochoa-Repáraz, Javier; Kasper, Lloyd H

    2014-08-01

    There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination. PMID:25084177

  9. Distribution of paired immunoglobulin-like receptor B in the nervous system related to regeneration difficulties after unilateral lumbar spinal cord injury

    PubMed Central

    Peng, Wan-shu; Qi, Chao; Zhang, Hong; Gao, Mei-ling; Wang, Hong; Ren, Fei; Li, Xia-qing

    2015-01-01

    Paired immunoglobulin-like receptor B (PirB) is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of PirB on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of PirB (via immunofluorescence) in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for PirB increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, PirB was mainly distributed along neuronal and axonal membranes. PirB was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunoreactivity for PirB was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the findings suggest a pattern of PirB immunoreactivity in the nervous system after unilateral spinal transection injury, and also indicate that PirB may suppress repair after injury. PMID:26330840

  10. Adaptation of the ammoniacal silver reaction to cytochemical demonstration of myelin basic protein.

    PubMed

    Staykova, M; Jordanov, J; Goranov, I

    1978-01-01

    A modification of Black and Ansley's ammoniacal silver reaction (ASR) for histones is proposed for visualizing myelin basic protien (MBP) in the nervous system. The reaction is performed on histological sections of tissues fixed in neutralized formalin-alcohol and delipidized in the course of the routine paraffin embedding. The deparaffinized sections are again treated with formalin in order to make the "unmasked" by the delipidization basic groups of MBP reactive to ammoniacal silver. After treatment with this reagent MBP of the myelin sheaths of the nerve fibres is impregnated brownish-black. Deparaffinized sections subjected to an extraction of MBP with hydrochloric acid exhibit a negative reaction at the level of the myelin sheaths the same reaction being preserved at the level of the nuclear histones. The reaction is positive in paper spots of nervous tissue extracts obtained with the same acid. These assays indicate the specificity of the modified ASR. The method can be used for studies on the processes of myelination and demylination in normal histogenesis and in pathology of the nervous tissue.

  11. Development of Myelination and Cholinergic Innervation in the Central Auditory System of a Prosimian Primate (Otolemur garnetti)

    PubMed Central

    Miller, Daniel J.; Lackey, Elizabeth P.; Hackett, Troy A.; Kaas, Jon H.

    2014-01-01

    Change in the timeline of neurobiological growth is an important source of biological variation, and thus phenotypic evolution. However, no study has to date investigated sensory system development in any of the prosimian primates that are thought to most closely resemble our earliest primate ancestors. Acetylcholine (ACh) is a neurotransmitter critical to normal brain function by regulating synaptic plasticity associated with attention and learning. Myelination is an important structural component of the brain because it facilitates rapid neuronal communication. In this work we investigated the expression of acetylcholinesterase (AChE) and the density of myelinated axons throughout post-natal development in the inferior colliculus (IC), medial geniculate complex (MGC), and auditory cortex (auditory core, belt, and parabelt) in Garnett’s greater galago (Otolemur garnetti). We found that the IC and MGC exhibit relatively high myelinated fiber length density (MFLD) values at birth and attain adult-like values by the species-typical age at weaning. In contrast, neocort-ical auditory fields are relatively unmyelinated at birth and only attain adult-like MFLD values by the species-typical age at puberty. Analysis of AChE expression indicated that, in contrast to evidence from rodent samples, the adult-like distribution of AChE in the core area of auditory cortex, dense bands in layers I, IIIb/IV, and Vb/VI, is present at birth. These data indicate the differential developmental trajectory of central auditory system structures and demonstrate the early onset of adult-like AChE expression in primary auditory cortex in O. garnetti, suggesting the auditory system is more developed at birth in primates compared to rodents. PMID:23749337

  12. Age-related decline of myelin proteins is highly correlated with activation of astrocytes and microglia in the rat CNS.

    PubMed

    Xie, Fang; Zhang, Jiu-Cong; Fu, Han; Chen, Jun

    2013-11-01

    It has been shown that aging can greatly influence the integrity and ultrastructure of white matter and the myelin sheath; however, studies regarding the effects of aging on the expression of myelin proteins are still limited. In the present study, immunohistochemical mapping was used to investigate the overall expression of myelin basic protein (Mbp) and myelin oligodendrocyte glycoprotein (Mog) in the central nervous system (CNS) of rats in postnatal months 2, 5, 18 and 26. Astrocyte and microglia activation was also detected by glial fibrillary acidic protein (GFAP) or ionized calcium-binding adaptor molecule 1 (Iba1) staining and western blotting. A significant decline of Mbp and Mog was identified as a universal alteration in the CNS of aged rats. Aging also induced significant astrocyte and microglial activation. Correlation analysis indicated a negative correlation between the reduction of age‑related myelin proteins and glial activation in aging. This correlation of myelin breakdown and glial activation in aging may reveal new evidence in connecting the inflammation and myelin breakdown mechanism of age‑related neurodegenerative diseases.

  13. The origin and evolution of chordate nervous systems.

    PubMed

    Holland, Linda Z

    2015-12-19

    In the past 40 years, comparisons of developmental gene expression and mechanisms of development (evodevo) joined comparative morphology as tools for reconstructing long-extinct ancestral forms. Unfortunately, both approaches typically give congruent answers only with closely related organisms. Chordate nervous systems are good examples. Classical studies alone left open whether the vertebrate brain was a new structure or evolved from the anterior end of an ancestral nerve cord like that of modern amphioxus. Evodevo plus electron microscopy showed that the amphioxus brain has a diencephalic forebrain, small midbrain, hindbrain and spinal cord with parts of the genetic mechanisms for the midbrain/hindbrain boundary, zona limitans intrathalamica and neural crest. Evodevo also showed how extra genes resulting from whole-genome duplications in vertebrates facilitated evolution of new structures like neural crest. Understanding how the chordate central nervous system (CNS) evolved from that of the ancestral deuterostome has been truly challenging. The majority view is that this ancestor had a CNS with a brain that gave rise to the chordate CNS and, with loss of a discrete brain, to one of the two hemichordate nerve cords. The minority view is that this ancestor had no nerve cord; those in chordates and hemichordates evolved independently. New techniques such as phylostratigraphy may help resolve this conundrum.

  14. Central nervous system effects of local anaesthetic agents.

    PubMed

    Englesson, S; Matousek, M

    1975-02-01

    A review is given of an experimental study on cats where the influence of acid-base changes on central nervous system toxicity of local anaesthetic agents was studied. The conclusion of this study was that a respiratory acidosis increased the central nervous system toxicity of local anaesthetics and that the underlying metabolic conditions modified this increase. Thus a respiratory acidosis increased this toxicity more if it was based on a metabolic acidosis than on a metabolic alkalosis (Englesson, 1974; Englesson and Grevsten, 1974). An extended analysis is presented where automatic frequency analysis was performed on the e.e.g. recordings performed during the i.v. infusion of lignocaine, bupivacaine, L 134, HS 37 and its optical isomers. The preliminary results show that the electrical changes appearing in the e.e.g. from the start of the i.v. infusion until seizure activity were the same if this time interval was as short as 1 min or as long as 8 min. It also revealed remarkable individual differences between agents, for instance lignocaine displaying marked electrical changes already in the first third of this time period where bupivacaine showed no changes until shortly before seizures. PMID:238556

  15. TrkB/BDNF signalling patterns the sympathetic nervous system.

    PubMed

    Kasemeier-Kulesa, Jennifer C; Morrison, Jason A; Lefcort, Frances; Kulesa, Paul M

    2015-01-01

    The sympathetic nervous system is essential for maintaining mammalian homeostasis. How this intricately connected network, composed of preganglionic neurons that reside in the spinal cord and post-ganglionic neurons that comprise a chain of vertebral sympathetic ganglia, arises developmentally is incompletely understood. This problem is especially complex given the vertebral chain of sympathetic ganglia derive secondarily from the dorsal migration of 'primary' sympathetic ganglia that are initially located several hundred microns ventrally from their future pre-synaptic partners. Here we report that the dorsal migration of discrete ganglia is not a simple migration of individual cells but a much more carefully choreographed process that is mediated by extensive interactions of pre-and post-ganglionic neurons. Dorsal migration does not occur in the absence of contact with preganglionic axons, and this is mediated by BDNF/TrkB signalling. Thus BDNF released by preganglionic axons acts chemotactically on TrkB-positive sympathetic neurons, to pattern the developing peripheral nervous system. PMID:26404565

  16. [Components of plastic disrupt the function of the nervous system].

    PubMed

    Szychowski, Konrad Andrzej; Wójtowicz, Anna Katarzyna

    2013-05-27

    Development of the chemical industry leads to the development of new chemical compounds, which naturally do not exist in the environment. These chemicals are used to reduce flammability, increase plasticity, or improve solubility of other substances. Many of these compounds, which are components of plastic, the new generation of cosmetics, medical devices, food packaging and other everyday products, are easily released into the environment. Many studies have shown that a major lipophilicity characterizes substances such as phthalates, BPA, TBBPA and PCBs. This feature allows them to easily penetrate into living cells, accumulate in the tissues and the organs, and affect human and animal health. Due to the chemical structures, these compounds are able to mimic some endogenous hormones such as estradiol and to disrupt the hormone homeostasis. They can also easily pass the placental barrier and the blood-brain barrier. As numerous studies have shown, these chemicals disturb the proper functions of the nervous system from the earliest moments of life. It has been proven that these compounds affect neurogenesis as well as the synaptic transmission process. As a consequence, they interfere with the formation of the sex of the brain, as well as with the learning processes, memory and behavior. Additionally, the cytotoxic and pro-apoptotic effect may cause neurodegenerative diseases. This article presents the current state of knowledge about the effects of phthalates, BPA, TBBPA, and PCBs on the nervous system.

  17. Spectral Mixing in Nervous Systems: Experimental Evidenceand Biologically Plausible Circuits

    NASA Astrophysics Data System (ADS)

    Kleinfeld, D.; Mehta, S. B.

    The ability to compute the difference frequency for two periodic signals depends on a nonlinear operation that mixes those signals. Behavioral and psychophysical evidence suggest that such mixing is likely to occur in the vertebrate nervous system as a means to compare rhythmic sensory signals, such as occurs in human audition, and as a means to lock an intrinsic rhythm to a sensory input. Electrophysiological data from electroreceptors in the immobilized electric fish and somatosensory cortex in the anesthetized rat yield direct evidence for such mixing, providing a neurological substrate for the modulation and demodulation of rhythmic neuronal signals. We consider an analytical model of spectral mixing that makes use of the threshold characteristics of neuronal firing and which has features consistent with the experimental observations. This model serves as a guide for constructing circuits that isolate given mixture components. In particular, such circuits can generate nearly pure difference tones from sinusoidal inputs without the use of band-pass filters, in analogy to an image-reject mixer in communications engineering. We speculate that such computations may play a role in coding of sensory input and feedback stabilization of motor output in nervous systems.

  18. Glycosaminoglycans and glycomimetics in the central nervous system.

    PubMed

    Rowlands, Dáire; Sugahara, Kazuyuki; Kwok, Jessica C F

    2015-02-19

    With recent advances in the construction of synthetic glycans, selective targeting of the extracellular matrix (ECM) as a potential treatment for a wide range of diseases has become increasingly popular. The use of compounds that mimic the structure or bioactive function of carbohydrate structures has been termed glycomimetics. These compounds are mostly synthetic glycans or glycan-binding constructs which manipulate cellular interactions. Glycosaminoglycans (GAGs) are major components of the ECM and exist as a diverse array of differentially sulphated disaccharide units. In the central nervous system (CNS), they are expressed by both neurons and glia and are crucial for brain development and brain homeostasis. The inherent diversity of GAGs make them an essential biological tool for regulating a complex range of cellular processes such as plasticity, cell interactions and inflammation. They are also involved in the pathologies of various neurological disorders, such as glial scar formation and psychiatric illnesses. It is this diversity of functions and potential for selective interventions which makes GAGs a tempting target. In this review, we shall describe the molecular make-up of GAGs and their incorporation into the ECM of the CNS. We shall highlight the different glycomimetic strategies that are currently being used in the nervous system. Finally, we shall discuss some possible targets in neurological disorders that may be addressed using glycomimetics.

  19. Probing disorders of the nervous system using reprogramming approaches

    PubMed Central

    Ichida, Justin K; Kiskinis, Evangelos

    2015-01-01

    The groundbreaking technologies of induced pluripotency and lineage conversion have generated a genuine opportunity to address fundamental aspects of the diseases that affect the nervous system. These approaches have granted us unrestricted access to the brain and spinal cord of patients and have allowed for the study of disease in the context of human cells, expressing physiological levels of proteins and under each patient's unique genetic constellation. Along with this unprecedented opportunity have come significant challenges, particularly in relation to patient variability, experimental design and data interpretation. Nevertheless, significant progress has been achieved over the past few years both in our ability to create the various neural subtypes that comprise the nervous system and in our efforts to develop cellular models of disease that recapitulate clinical findings identified in patients. In this Review, we present tables listing the various human neural cell types that can be generated and the neurological disease modeling studies that have been reported, describe the current state of the field, highlight important breakthroughs and discuss the next steps and future challenges. PMID:25925386

  20. Sequelae of central-nervous-system enterovirus infections.

    PubMed

    Sells, C J; Carpenter, R L; Ray, C G

    1975-07-01

    The long-term effects of central-nervous-system enterovirus infections were examined in a controlled follow-up study of 19 children 2 1/2 to eight years of age who had been hospitalized with documented enterovirus infection 17 to 67 months before evaluation. Assessment included medical history, physical and neurologic examination, psychologic testing, and speech and hearing evaluation. Three children (16 per cent) had definite neurologic impairment, five (26 per cent) had possible impairment, and 11 (58 per cent) were free of detectable abnormalities. Children whose illness occurred during the first year of life, when compared to controls, were found to have significantly smaller mean head circumference (50.6 vs. 51.6 cm, P less than 0.033), significantly lower mean I.Q. (97 vs 115, P less than 0.007), and depressed languange and speech skills. Children whose illness occurred after the first year of life were not different from their controls. Children whith central-nervous-system enterovirus infection may have neurologic impairment when infection occurs in the first year of life.

  1. Role of the autonomic nervous system in modulating cardiac arrhythmias.

    PubMed

    Shen, Mark J; Zipes, Douglas P

    2014-03-14

    The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.

  2. Methanol intoxication: pathological changes of central nervous system (17 cases).

    PubMed

    Karayel, Ferah; Turan, Arzu A; Sav, Aydin; Pakis, Isil; Akyildiz, Elif U; Ersoy, Gokhan

    2010-03-01

    The nervous system has increased susceptibility for methanol intoxication. The aim of this study is to investigate various central nervous system lesions of methanol intoxication in 17 cases autopsied in the mortuary department of the Council of Forensic Medicine in Istanbul, Turkey. The reasons of methanol intoxication in the cases was likely the unwitting ingestion of methanol while drinking illegal alcohol. Survival times ranged from several hours to days. In 8 cases (47%), cerebral edema and in 9 cases (53%) at occipital, temporal and parietal cortex, basal ganglia and pons, petechial bleeding was observed. In addition to these findings, hemorrhagic necrosis were observed in thalamus, putamen, and globus pallidus in 5 cases (29.4%) and, in cerebral cortex in another 3 cases (17.6%). In 3 of the cases (17.6%) in which cerebral edema was found, herniation findings accompanied to the situation and in 2 cases (11.7%), pons bleeding was observed. Around the basal ganglia, in 2 of the cases with hemorrhagic necrosis, the situation ended with a ventricular compression. In 7 cases (41%), the associated findings of chronic ischemic changes in cortical neurons, lacunae formation, degeneration of granular cell layer of the cerebellum, and reactive gliosis were considered as the results of chronic alcoholism.

  3. Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

    PubMed Central

    Campbell, Preston; Ma, Yun

    2013-01-01

    The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the kidney and possibly the pancreas and gonads. It is thus becoming widely recognized that it is by nature an endocrine organ, in addition to a structural organ and site of mineral storage and hematopoiesis. Consequently and by definition, bone homeostasis must be tightly regulated and integrated with the biology of other organs to maintain whole body homeostasis, and data uncovering the involvement of the central nervous system (CNS) in the control of bone remodeling support this concept. The sympathetic nervous system (SNS) represents one of the main links between the CNS and the skeleton, based on a number of anatomic, pharmacologic, and genetic studies focused on β-adrenergic receptor (βAR) signaling in bone cells. The goal of this report was to review the data supporting the role of the SNS and βAR signaling in the regulation of skeletal homeostasis. PMID:23765388

  4. Astrocyte scar formation aids central nervous system axon regeneration.

    PubMed

    Anderson, Mark A; Burda, Joshua E; Ren, Yilong; Ao, Yan; O'Shea, Timothy M; Kawaguchi, Riki; Coppola, Giovanni; Khakh, Baljit S; Deming, Timothy J; Sofroniew, Michael V

    2016-04-14

    Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration. PMID:27027288

  5. Fine structure of synaptogenesis in the vertebrate central nervous system.

    PubMed

    Vaughn, J E

    1989-01-01

    This article reviews studies of the formation of synaptic junctions in the vertebrate central nervous system. It is focused on electron microscopic investigations of synaptogenesis, although insights from other disciplines are interwoven where appropriate, as are findings from developing peripheral and invertebrate nervous systems. The first part of the review is concerned with the morphological maturation of synapses as described from both qualitative and quantitative perspectives. Next, epigenetic influences on synaptogenesis are examined, and later in the article the concept of epigenesis is integrated with that of hierarchy. It is suggested that the formation of synaptic junctions may take place as an ordered progression of epigenetically modulated events wherein each level of cellular affinity becomes subordinate to the one that follows. The ultimate determination of whether a synapse is maintained, modified or dissolved would be made by the changing molecular fabric of its junctional membranes. In closing, a hypothetical model of synaptogenesis is proposed, and an hierarchial order of events is associated with a speculative synaptogenic sequence. Key elements of this hypothesis are 1) epigenetic factors that facilitate generally appropriate interactions between neurites; 2) independent expression of surface specializations that contain sufficient information for establishing threshold recognition between interacting neurites; 3) exchange of molecular information that biases the course of subsequent junctional differentiation and ultimately results in 4) the stabilization of synaptic junctions into functional connectivity patterns. PMID:2655146

  6. Neurotrophic effects of neudesin in the central nervous system

    PubMed Central

    Kimura, Ikuo; Nakayama, Yoshiaki; Zhao, Ying; Konishi, Morichika; Itoh, Nobuyuki

    2013-01-01

    Neudesin (neuron-derived neurotrophic factor; NENF) was identified as a neurotrophic factor that is involved in neuronal differentiation and survival. It is abundantly expressed in the central nervous system, and its neurotrophic activity is exerted via the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. Neudesin is also an anorexigenic factor that suppresses food intake in the hypothalamus. It is a member of the membrane-associated progesterone receptor (MAPR) family and shares key structural motifs with the cytochrome b5-like heme/steroid-binding domain. Progesterone receptor membrane component 1 (PGRMC1), the first to be discovered among the MAPR family, binds progesterone to induce “rapid non-genomic effects” in biological responses that are unrelated to the nuclear progesterone receptors (PRs). Hence, neudesin may also be involved in the rapid non-genomic actions of progesterone. In this review, we summarize the identification, structure, and activity of neudesin in the central nervous system, and present an essential overview of the current understanding of its physiological roles and the prospect of elucidating its non-genomic progesterone effects. PMID:23805070

  7. Engineering Biomaterial Properties for Central Nervous System Applications

    NASA Astrophysics Data System (ADS)

    Rivet, Christopher John

    Biomaterials offer unique properties that are intrinsic to the chemistry of the material itself or occur as a result of the fabrication process; iron oxide nanoparticles are superparamagnetic, which enables controlled heating in the presence of an alternating magnetic field, and a hydrogel and electrospun fiber hybrid material provides minimally invasive placement of a fibrous, artificial extracellular matrix for tissue regeneration. Utilization of these unique properties towards central nervous system disease and dysfunction requires a thorough definition of the properties in concert with full biological assessment. This enables development of material-specific features to elicit unique cellular responses. Iron oxide nanoparticles are first investigated for material-dependent, cortical neuron cytotoxicity in vitro and subsequently evaluated for alternating magnetic field stimulation induced hyperthermia, emulating the clinical application for enhanced chemotherapy efficacy in glioblastoma treatment. A hydrogel and electrospun fiber hybrid material is first applied to a rat brain to evaluate biomaterial interface astrocyte accumulation as a function of hybrid material composition. The hybrid material is then utilized towards increasing functional engraftment of dopaminergic progenitor neural stem cells in a mouse model of Parkinson's disease. Taken together, these two scenarios display the role of material property characterization in development of biomaterial strategies for central nervous system repair and regeneration.

  8. Targeted Temperature Management in Pediatric Central Nervous System Disease

    PubMed Central

    Newmyer, Robert; Mendelson, Jenny; Pang, Diana; Fink, Ericka L.

    2015-01-01

    Opinion Statement Acute central nervous system conditions due to hypoxic-ischemic encephalopathy, traumatic brain injury (TBI), status epilepticus, and central nervous system infection/inflammation, are a leading cause of death and disability in childhood. There is a critical need for effective neuroprotective therapies to improve outcome targeting distinct disease pathology. Fever, defined as patient temperature > 38°C, has been clearly shown to exacerbate brain injury. Therapeutic hypothermia (HT) is an intervention using targeted temperature management that has multiple mechanisms of action and robust evidence of efficacy in multiple experimental models of brain injury. Prospective clinical evidence for its neuroprotective efficacy exists in narrowly-defined populations with hypoxic-ischemic injury outside of the pediatric age range while trials comparing hypothermia to normothermia after TBI have failed to demonstrate a benefit on outcome but consistently demonstrate potential use in decreasing refractory intracranial pressure. Data in children from prospective, randomized controlled trials using different strategies of targeted temperature management for various outcomes are few but a large study examining HT versus controlled normothermia to improve neurological outcome in cardiac arrest is underway. PMID:26042193

  9. Does the Sympathetic Nervous System Adapt to Chronic Altitude Exposure?

    PubMed

    Sander, Mikael

    2016-01-01

    During continued exposure to hypobaric hypoxia in acclimatizing lowlanders increasing norepinephrine levels indirectly indicate sympathoexcitation, and in a few subjects serial measurements have suggested some adaptation over time. A few studies have provided direct microneurographic evidence for markedly increased muscle sympathetic nervous activity (MSNA) after 1-50 days of exposure of lowlanders to altitudes of 4100-5260 m above sea level. Only one study has provided two MSNA-measurements over time (10 and 50 days) in altitude (4100 m above sea level) and continued robust sympathoexcitation without adaptation was found in acclimatizing lowlanders. In this study, norepinephrine levels during rest and exercise also remained highly elevated over time. In comparison, acute exposure to hypoxic breathing (FiO2 0.126) at sea level caused no change in sympathetic nervous activity, although the same oxygen saturation in arterial blood (around 90 %) was present during acute (FiO2 0.126) and chronic hypoxic exposure (4100 m above sea level). These findings strongly suggest that the chemoreflex-mechanisms underlying acute hypoxia-induced increases in MSNA are sensitized over time. Collectively, the MSNA data suggests that sensitization of the sympathoexcitatory chemoreflex is evident but not complete within the first 24 h, but is complete after 10 days of altitude exposure. After return from high altitude to sea level the MSNA remains significantly elevated for at least 5 days but completely normalized after 3 months. The few MSNA measurements in high altitude natives have documented high sympathetic activity in all subjects studied. Because serial measurements of MSNA in high altitude natives during sea level exposure are lacking, it is unclear whether the sympathetic nervous system have somehow adapted to lifelong altitude exposure. PMID:27343109

  10. MYELIN, COPPER, AND THE CUPRIZONE MODEL OF SCHIZOPHRENIA

    PubMed Central

    Herring, Nicole R.; Konradi, Christine

    2010-01-01

    In recent years increasing evidence is pointing toward white matter abnormalities in schizophrenia and other psychiatric disorders. The present paper will provide an overview over the role of myelin in cognition and brain function, and its potential involvement in brain disorders. Furthermore, we will examine one particular experimental model for the study of dysmyelination, created by the administration of the toxin cuprizone. Cuprizone, a copper chelator, causes white matter abnormalities in rodents. The administration of cuprizone during specific developmental periods allows for the targeting of specific brain areas for dysmyelination. Thus, cuprizone can be used to study the pathogenesis and pathophysiology of myelin deficiencies in the central nervous system, and its effect on behaviors relevant to psychiatric disorders. PMID:21196354

  11. Breast Cancer Metastasis to the Central Nervous System

    PubMed Central

    Weil, Robert J.; Palmieri, Diane C.; Bronder, Julie L.; Stark, Andreas M.; Steeg, Patricia S.

    2005-01-01

    Clinically symptomatic metastases to the central nervous system (CNS) occur in ∼10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding. PMID:16192626

  12. Breast cancer metastasis to the central nervous system.

    PubMed

    Weil, Robert J; Palmieri, Diane C; Bronder, Julie L; Stark, Andreas M; Steeg, Patricia S

    2005-10-01

    Clinically symptomatic metastases to the central nervous system (CNS) occur in approximately 10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding. PMID:16192626

  13. Multifaceted interactions between adaptive immunity and the central nervous system.

    PubMed

    Kipnis, Jonathan

    2016-08-19

    Neuroimmunologists seek to understand the interactions between the central nervous system (CNS) and the immune system, both under homeostatic conditions and in diseases. Unanswered questions include those relating to the diversity and specificity of the meningeal T cell repertoire; the routes taken by immune cells that patrol the meninges under healthy conditions and invade the parenchyma during pathology; the opposing effects (beneficial or detrimental) of these cells on CNS function; the role of immune cells after CNS injury; and the evolutionary link between the two systems, resulting in their tight interaction and interdependence. This Review summarizes the current standing of and challenging questions related to interactions between adaptive immunity and the CNS and considers the possible directions in which these aspects of neuroimmunology will be heading over the next decade. PMID:27540163

  14. The border between the central and the peripheral nervous system in the cat cochlear nerve: a light and scanning electron microscopical study.

    PubMed

    Osen, Kirsten K; Furness, David N; Hackney, Carole M

    2011-07-01

    The transition between the central (CNS) and peripheral nervous system (PNS) in cranial and spinal nerve roots, referred to here as the CNS-PNS border, is of relevance to nerve root disorders and factors that affect peripheral-central regeneration. Here, this border is described in the cat cochlear nerve using light microscopical sections, and scanning electron microscopy of the CNS-PNS interfaces exposed by fracture of the nerve either prior to or following critical point drying. The CNS-PNS border represents an abrupt change in type of myelin, supporting elements, and vascularization. Because central myelin is formed by oligodendrocytes and peripheral myelin by Schwann cells, the myelinated fibers are as a rule equipped with a node of Ranvier at the border passage. The border is shallower and smoother in cat cochlear nerve than expected from other nerves, and the borderline nodes are largely in register. The loose endoneurial connective tissue of the PNS compartment is closed at the border by a compact glial membrane, the mantle zone, of the CNS compartment. The mantle zone is penetrated by the nerve fibers, but is otherwise composed of astrocytes and their interwoven processes like the external limiting membrane of the brain surface with which it is continuous. The distal surface of the mantle zone is covered by a fenestrated basal lamina. Only occasional vessels traverse the border. From an anatomical point of view, the border might be expected to be a weak point along the cochlear nerve and thus vulnerable to trauma. In mature animals, the CNS-PNS border presents a barrier to regrowth of regenerating nerve fibers and to invasion of the CNS by Schwann cells. An understanding of this region in the cochlear nerve is therefore relevant to head injuries that lead to hearing loss, to surgery on acoustic Schwannomas, and to the possibility of cochlear nerve regeneration.

  15. Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

    PubMed

    Kornfeld, Samantha F; Lynch-Godrei, Anisha; Bonin, Sawyer R; Gibeault, Sabrina; De Repentigny, Yves; Kothary, Rashmi

    2016-01-01

    Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as was myelin basic

  16. Bisphenol-A impairs myelination potential during development in the hippocampus of the rat brain.

    PubMed

    Tiwari, Shashi Kant; Agarwal, Swati; Chauhan, Lalit Kumar Singh; Mishra, Vijay Nath; Chaturvedi, Rajnish Kumar

    2015-01-01

    Myelin is the functional implication of oligodendrocytes (OLs), which is involved in insulation of axons and promoting rapid propagation of action potential in the brain. OLs are derived from oligodendrocyte progenitor cells (OPCs), which proliferate, differentiate, and migrate throughout the central nervous system. Defects in myelination process lead to the onset of several neurological and neurodegenerative disorders. Exposure to synthetic xenoestrogen bisphenol-A (BPA) causes cognitive dysfunction, impairs hippocampal neurogenesis, and causes onset of neurodevelopmental disorders. However, the effects of BPA on OPC proliferation, differentiation and myelination, and associated cellular and molecular mechanism(s) in the hippocampus of the rat brain are still largely unknown. We found that BPA significantly decreased bromodeoxyuridine (BrdU)-positive cell proliferation and number and size of oligospheres. We observed reduced co-localization of BrdU with myelination markers CNPase and platelet-derived growth factor receptor-α (PDGFR-α), suggesting impaired proliferation and differentiation of OPCs by BPA in culture. We studied the effects of BPA exposure during prenatal and postnatal periods on cellular and molecular alteration(s) in the myelination process in the hippocampus region of the rat brain at postnatal day 21 and 90. BPA exposure both in vitro and in vivo altered proliferation and differentiation potential of OPCs and decreased the expression of genes and levels of proteins that are involved in myelination. Ultrastructural electron microscopy analysis revealed that BPA exposure caused decompaction of myelinated axons and altered g-ratio at both the developmental periods as compared to control. These results suggest that BPA exposure both during prenatal and postnatal periods alters myelination in the hippocampus of the rat brain leading to cognitive deficits.

  17. Gestational nicotine exposure modifies myelin gene expression in the brains of adolescent rats with sex differences.

    PubMed

    Cao, J; Wang, J; Dwyer, J B; Gautier, N M; Wang, S; Leslie, F M; Li, M D

    2013-04-16

    Myelination defects in the central nervous system (CNS) are associated with various psychiatric disorders, including drug addiction. As these disorders are often observed in individuals prenatally exposed to cigarette smoking, we tested the hypothesis that such exposure impairs central myelination in adolescence, an important period of brain development and the peak age of onset of psychiatric disorders. Pregnant Sprague Dawley rats were treated with nicotine (3 mg kg(-1) per day; gestational nicotine (GN)) or gestational saline via osmotic mini pumps from gestational days 4-18. Both male and female offsprings were killed on postnatal day 35 or 36, and three limbic brain regions, the prefrontal cortex (PFC), caudate putamen and nucleus accumbens, were removed for measurement of gene expression and determination of morphological changes using quantitative real-time PCR (qRT-PCR) array, western blotting and immunohistochemical staining. GN altered myelin gene expression at both the mRNA and protein levels, with striking sex differences. Aberrant expression of myelin-related transcription and trophic factors was seen in GN animals, which correlated highly with the alterations in the myelin gene expression. These correlations suggest that these factors contribute to GN-induced alterations in myelin gene expression and also indicate abnormal function of oligodendrocytes (OLGs), the myelin-producing cells in the CNS. It is unlikely that these changes are attributable solely to an alteration in the number of OLGs, as the cell number was changed only in the PFC of GN males. Together, our findings suggest that abnormal brain myelination underlies various psychiatric disorders and drug abuse associated with prenatal exposure to cigarette smoke.

  18. Nav1.8 expression is not restricted to nociceptors in mouse peripheral nervous system.

    PubMed

    Shields, Shannon D; Ahn, Hye-Sook; Yang, Yang; Han, Chongyang; Seal, Rebecca P; Wood, John N; Waxman, Stephen G; Dib-Hajj, Sulayman D

    2012-10-01

    A vast diversity of salient cues is sensed by numerous classes of primary sensory neurons, defined by specific neuropeptides, ion channels, or cytoskeletal proteins. Recent evidence has demonstrated a correlation between the expression of some of these molecular markers and transmission of signals related to distinct sensory modalities (eg, heat, cold, pressure). Voltage-gated sodium channel Na(v)1.8 has been reported to be preferentially expressed in small-diameter unmyelinated sensory afferents specialized for the detection of noxious stimuli (nociceptors), and Na(v)1.8-Cre mice have been widely used to investigate gene function in nociceptors. However, the identity of neurons in which Cre-mediated recombination occurs in these animals has not been resolved, and whether expression of Na(v)1.8 in these neurons is dynamic during development is not known, rendering interpretation of conditional knockout mouse phenotypes problematic. Here, we used genetics, immunohistochemistry, electrophysiology, and calcium imaging to precisely characterize the expression of Na(v)1.8 in the peripheral nervous system. We demonstrate that 75% of dorsal root ganglion (DRG) neurons express Na(v)1.8-Cre, including >90% of neurons expressing markers of nociceptors and, unexpectedly, a large population (∼40%) of neurons with myelinated A fibers. Furthermore, analysis of DRG neurons' central and peripheral projections revealed that Na(v)1.8-Cre is not restricted to nociceptors but is also expressed by at least 2 types of low-threshold mechanoreceptors essential for touch sensation, including those with C and Aβ fibers. Our results indicate that Na(v)1.8 underlies electrical activity of sensory neurons subserving multiple functional modalities, and call for cautious interpretation of the phenotypes of Na(v)1.8-Cre-driven conditional knockout mice. PMID:22703890

  19. Nonlinear optical techniques for imaging and manipulating the mouse central nervous system

    NASA Astrophysics Data System (ADS)

    Farrar, Matthew John

    The spinal cord of vertebrates serves as the conduit for somatosensory information and motor control, as well as being the locus of neural circuits that govern fast reflexes and patterned behaviors, such as walking in mammals or swimming in fish. Consequently, pathologies of the spinal cord -such as spinal cord injury (SCI)- lead to loss of motor control and sensory perception, with accompanying decline in life expectancy and quality of life. Despite the devastating effects of these diseases, few therapies exist to substantially ameliorate patient outcome. In part, studies of spinal cord pathology have been limited by the inability to perform in vivo imaging at the level of cellular processes. The focus of this thesis is to present the underlying theory for and demonstration of novel multi-photon microscopy (MPM) and optica