Home About us Contact
|
Home About us Contact | ||
|
|
||
Peripheral Nervous System (peripheral + nervous_system)
Terms modified by Peripheral Nervous System Selected AbstractsA 71-YEAR-OLD MALE WITH 4 DECADES OF SYMPTOMS REFERABLE TO BOTH CENTRAL AND PERIPHERAL NERVOUS SYSTEMBRAIN PATHOLOGY, Issue 4 2005Dianna Quan MD First page of article [source] Workshop 5: NAAG and NAALADase: Functional Properties in the Central and Peripheral Nervous SystemJOURNAL OF NEUROCHEMISTRY, Issue 2002D. Bacich Glutamate carboxypeptidase II (GCPII, also known as N-acetylated-alpha-linked acidic dipeptidase or NAALADase) knockout (KO) mice were generated by inserting a GCPII targeting cassette containing a PGK-Neo resistance marker and stop codons in exons 1 and 2, and removal of exons 1 and 2 intron/exon boundary sequence. Embryonic stem cells were injected into C57BL6 blastocysts, and chimeric offspring born. Germline transmission was confirmed by mating the chimeras to generate heterozygous KO mice. Crossing heterozygous mice generated F2 generation mice homozygous for the null mutant, as confirmed by loss of GCPII protein. NAAG hydrolyzing activity was minimal (0.07 pmol/mg/min) in KO tissue, with normal levels (4.82 pmol/mg/min) in wild types and intermediate levels (1.73 pmol/mg/min) in heterozygotes. Preliminary neuropathy experiments showed KO mice are less affected by nerve-crush and recover faster from the damage-induced neuropathy, as indicated by EMG recording and nerve morphology. Similarly, GCPII KO mice subjected to high dose vitamin B6 displayed less severe neuropathy than wild types, as indicated by reduced sensory nerve conduction velocity and morphological deficits. Also, in a transient middle cerebral artery occlusion model, GCPII KO mice were significantly more resistant to the effects of cerebral ischemia than their wildtype littermates. Findings support GCPII involvement in stroke and in mediating chronic neuropathic conditions and suggest GCPII inhibitors may be useful in treatment of brain ischemia as well as peripheral neuropathies. [source] 2007 impact factor for the Journal of the Peripheral Nervous System: 2.943JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2008David R. Cornblath Editor-in-Chief [source] Nogo A expression in the adult enteric nervous systemNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2004S. L. Osborne Abstract, Neuronal plasticity plays an important role in physiological and pathological processes within the gastrointestinal (GI) tract. Nogo A is a major contributor to the negative effect central nervous system (CNS) myelin has on neurite outgrowth after injury and may also play a role in maintaining synaptic connections in the healthy CNS. Nogo A is highly expressed during neuronal development but in the CNS declines postnatally concomitantly with a loss of regenerative potential while ganglia of the Peripheral Nervous System (PNS) retain Nogo A. The enteric nervous system shares a number of features in common with the CNS, thus the peripheral distribution of factors affecting plasticity is of interest. We have investigated the distribution of Nogo in the adult mammalian gastrointestinal tract. Nogo A mRNA and protein are detectable in the adult rat GI tract. Nogo A is expressed heterogeneously in enteric neurons throughout the GI tract though expression levels appear not to be correlated with neuronal sub-type. The pattern of expression is maintained in cultured myenteric plexus from the guinea-pig small intestine. As is seen in developing neurons of the CNS, enteric Nogo A is present in both neuronal cell bodies and axons. Our results point to a hitherto unsuspected role for Nogo A in enteric neuronal physiology. [source] A New Species of Myxozoa, Henneguya rondoni n. sp. (Myxozoa), from the Peripheral Nervous System of the Amazonian Fish, Gymnorhamphichthys rondoni (Teleostei)THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 3 2008CARLOS AZEVEDO ABSTRACT. Henneguya rondoni n. sp. found in the peripheral lateral nerves located below the two lateral lines of the fish Gymnorhamphichthys rondoni (Teleostei, Rhamphichthyidae) from the Amazon river is described using light and electron microscopy. Spherical to ellipsoid cysts measuring up to 110 ,m in length contained only immature and mature spores located in close contact with the myelin sheaths of the nervous fibres. Ellipsoidal spores measured 17.7 (16.9,18.1)-,m long, 3.6 (3.0,3.9)-,m wide, and 2.5 (2.2,2.8)-,m (n=25) thick. The spore body measuring 7.0 (6.8,7.3)-,m long was formed by two equal symmetric valves, each with an equal tapering tail 10.7 (10.3,11.0) ,m in length. The tails were composed of an internal dense material surrounded by an external homogeneous sheath of hyaline substance. The valves surrounded two equal pyriform polar capsules measuring 2.5 (2.2,2.8)-,m long and 0.85 (0.79,0.88)-,m (n=25) wide and a binucleated sporoplasm cell containing globular sporoplasmosomes 0.38 (0.33,0.42) ,m (n=25) in diam. with an internal eccentric dense structure with half-crescent section. Each polar capsule contains an anisofilar polar filament with 6,7 turns obliquely to the long axis. The matrix of the polar capsule was dense and the wall filled with a hyaline substance. The spores differed from those of previously described species. Based on the ultrastructural morphology of the spore and specificity to the host species, we propose a new species name H. rondoni n. sp. [source] Clinical, neuroimaging and neurophysiological features in addicts with manganese-ephedrone exposureACTA NEUROLOGICA SCANDINAVICA, Issue 4 2010K. Sikk Sikk K, Taba P, Haldre S, Bergquist J, Nyholm D, Askmark H, Danfors T, Sörensen J, Thurfjell L, Raininko R, Eriksson R, Flink R, Färnstrand C, Aquilonius S-M. Clinical, neuroimaging and neurophysiological features in addicts with manganese-ephedrone exposure. Acta Neurol Scand: 2010: 121: 237,243. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To identify biomarkers supporting the clinical diagnosis of manganism in patients several years after exposure to manganese (Mn). Methods,,, Neurophysiological examinations, magnetic resonance imaging (MRI), single-photon emission computed tomography and fluorodeoxyglycose (FDG) positron emission tomography were performed in four former ephedrone addicts with extrapyramidal symptoms. Results,,, Peripheral nervous system was not affected. No patients had reduced uptake of 123I Ioflupane in the striatum. MRI signal intensities were slightly changed in the basal ganglia. All patients showed a widespread, but not uniform, pathological pattern of FDG uptake with changes mainly located to the central part of the brain including the basal ganglia and the surrounding white matter. Conclusions,,, Presynaptic neurons in the nigrostriatal pathway are intact in Mn-induced parkinsonism after prolonged abstinence from ephedrone. The diagnosis is principally based on clinical signs and the history of drug abuse. [source] Clinical presentations of alopecia areataDERMATOLOGIC THERAPY, Issue 4 2001Maria K. Hordinsky Alopecia areata (AA) may can occur on any hair-bearing region. Patients can develop patchy nonscarring hair loss or extensive loss of all body hair. Hair loss may fluctuate. Some patients experience recurrent hair loss followed by hair regrowth, whereas others may only develop a single patch of hair loss, never to see the disease again. Still others experience extensive loss of body hair. The heterogeneity of clinical presentations has led investigators conducting clinical therapeutic trials to typically group patients into three major groups, those with extensive scalp hair loss [alopecia totalis (AT)], extensive body hair loss [alopecia universalis (AU)], or patchy disease (AA). Treatment outcomes have been correlated with disease duration and extent. Recently, guidelines were established for selecting and assessing subjects for both clinical and laboratory studies of AA, thereby facilitating collaboration, comparison of data, and the sharing of patient-derived tissue. For reporting purposes the terms AT and AU, though still used are defined very narrowly. AT is 100% terminal scalp hair loss without any body hair loss and AU is 100% terminal scalp hair and body loss. AT/AU is the term now recommended to define the presence of AT with variable amounts of body hair loss. In this report the term AA will be used broadly to encompass the many presentations of this disease. Development of AA may occur with changes in other ectodermal-derived structures such as fingernails and toenails. Some investigators have also suggested that other ectodermal-derived appendages as sebaceous glands and sweat glands may be affected in patients experiencing AA. Whether or not function of these glands is truly impaired remains to be confirmed. Many patients who develop patchy or extensive AA complain of changes in cutaneous sensation, that is, burning, itching, tingling, with the development of their disease. Similar symptoms may occur with hair regrowth. The potential involvement of the nervous system in AA has led to morphologic investigations of the peripheral nervous system as well as analysis of circulating neuropeptide levels. In this article the clinical presentations of AA are reviewed. The guidelines for conducting treatment studies of AA are presented and observations on changes in cutaneous innervation are introduced. Throughout the text, unless otherwise noted, AA will be used in a general way to denote the spectrum of this disease. [source] Sox genes regulate type 2 collagen expression in avian neural crest cellsDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 8 2006Takashi Suzuki Neural crest cells give rise to a wide variety of cell types, including cartilage cells in the cranium and neurons and glial cells in the peripheral nervous system. To examine the relationship of cartilage differentiation and neural crest differentiation, we examined the expression of Col2a1, which encodes type 2 collagen often used as a cartilage marker, and compared it with the expression of Sox transcription factor genes, which are involved in neural crest development and chondrogenesis. We found that Col2a1 is expressed in many neural crest-derived cell types along with combinations of Sox9, Sox10 and LSox5. Overexpression studies reveal the activation of Col2a1 expression by Sox9 and Sox10, and cross-regulation of these Sox genes. Luciferase assay indicates a direct activation of the Col2a1 enhancer/promoter both by Sox9 and Sox10, and this activation is further enhanced by cAMP-dependent kinase (PKA) signaling. Our study suggests that the regulatory mechanisms are similar in cartilage and neural crest differentiation. [source] Staying alive: Dalmatian mediated blocking of apoptosis is essential for tissue maintenanceDEVELOPMENTAL DYNAMICS, Issue 6 2010Bilal E. Kerman Abstract In an EMS screen for mutations disrupting tracheal development, we identified new alleles of the dalmation (dmt) gene, which had previously been shown to affect peripheral nervous system (PNS) development. Here, we demonstrate that dmt loss results in programmed cell death, disrupting PNS patterning and leading to large gaps in the salivary duct and trachea. Dmt loss results in increased expression of the proapoptotic regulator genes head involution defective (hid) and reaper (rpr), and deletion of these genes or tissue-specific expression of the baculoviral apoptotic inhibitor P35 rescues the dmt defects. dmt is also required to protect cells from irradiation induced expression of hid and rpr during the irradiation resistant stage, which begins as cells become irreversibly committed to their final fates. Thus, we propose that Dmt keeps cells alive by blocking activation of hid and rpr as cells become irreversibly committed. Developmental Dynamics 239:1609,1621, 2010. © 2010 Wiley-Liss, Inc. [source] Differential expression of sphingosine-1-phosphate receptors 1-5 in the developing nervous systemDEVELOPMENTAL DYNAMICS, Issue 2 2009H. Meng Abstract Sphingosine-1-phosphate (S1P) binds to G protein,coupled receptors and can regulate a wide range of cellular functions. In a previous study, we isolated two key enzymes in the S1P pathway that were expressed in migrating neural crest cells. To determine if S1P receptors are present in neural crest cells or peripheral nervous system, we examine the expression patterns of S1P receptors (S1pr1-5) in mouse, and s1pr1 and s1pr3 in chick embryos. Here, we present a comprehensive expression analysis of these receptors using in situ hybridizations, which provide spatiotemporal information. We showed that S1pr2 was expressed in migrating cranial neural crest cells and enteric neurons. S1pr1 was prominently expressed in the neuroepithelium whereas S1pr4 and S1pr5 were in neurons at later stages. On the contrary, S1pr3 was predominantly detected in non-neuronal cells within and surrounding neural structures. We also described novel expression sites for S1P receptors in the developing nervous system. Developmental Dynamics 238:487,500, 2009. © 2009 Wiley-Liss, Inc. [source] Identification of candidate secreted factors involved in trigeminal placode inductionDEVELOPMENTAL DYNAMICS, Issue 10 2007Kathryn L. McCabe Abstract Cranial ectodermal placodes are critical for normal development of the peripheral nervous system of the head. However, many aspects of the molecular and tissue interactions involved in their induction have yet to be elucidated. The trigeminal placode is induced by an unidentified secreted factor(s) from the dorsal neural tube. To determine candidates that may be involved in this induction process, we have performed reverse transcriptase-polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization to screen for receptors expressed by uninduced presumptive trigeminal level ectoderm. We have found that receptors for fibroblast growth factors, insulin-like growth factors, platelet-derived growth factors, Sonic hedgehog, the transforming growth factor-beta superfamily, and Wnts all are expressed in patterns consistent with a role in trigeminal placode formation. This RT-PCR screen for candidate receptors expressed in presumptive trigeminal ectoderm is the first systematic screen to identify potential interactions underlying induction of the trigeminal placode and represents a critical step for understanding this complex process. Developmental Dynamics 236:2925,2935, 2007. © 2007 Wiley-Liss, Inc. [source] Neural stem cells for the treatment of disorders of the enteric nervous system: Strategies and challengesDEVELOPMENTAL DYNAMICS, Issue 1 2007Maria-Adelaide Micci Abstract The main goal of this review is to summarize the status of the research in the field of stem cells transplantation, as it is applicable to the treatment of gastrointestinal motility. This field of research has advanced tremendously in the past 10 years, and recent data produced in our laboratories as well as others is contributing to the excitement on the use of neural stem cells (NSC) as a valuable therapeutic approach for disorders of the enteric nervous system characterized by a loss of critical neuronal subpopulations. There are several sources of NSC, and here we describe therapeutic strategies for NSC transplantation in the gut. These include using NSC as a relatively nonspecific cellular replacement strategy in conditions where large populations of neurons or their subsets are missing or destroyed. As with many other recent "breakthroughs" stem cell therapy may eventually prove to be overrated. However, at the present time, it does appear to provide the hope for a true cure for many currently intractable diseases of both the central and the peripheral nervous system. Certainly more extensive research is needed in this field. We hope that our review will encourage new investigators in entering this field of research ad contribute to our knowledge of the potentials of NSC and other cells for the treatment of gastrointestinal dysmotility. Developmental Dynamics 236:33,43, 2007. © 2006 Wiley-Liss, Inc. [source] cadherin-6 Message expression in the nervous system of developing zebrafishDEVELOPMENTAL DYNAMICS, Issue 1 2006Qin Liu Abstract Cadherins are cell surface adhesion molecules that play important roles in development of a variety of tissues including the nervous system. In this study, we analyzed expression pattern of cadherin-6, a member of the type II cadherin subfamily, in the embryonic zebrafish nervous system using in situ hybridization methods. cadherin-6 message is first expressed by the neural keel, then by restricted regions in the brain and spinal cord. cadherin-6 expression in the brain transiently delineates specific brain regions. In the peripheral nervous system, cadherin-6 message is expressed by the neurogenic placodes and the dorsal root ganglia. As development proceeds, cadherin-6 expression domain and/or expression levels increased in the embryonic nervous system. Our results show that cadherin-6 expression in the zebrafish developing nervous system is both spatially and temporally regulated, implicating a role for cadherin-6 in the formation of these nervous structures. Developmental Dynamics 235:272,278, 2006. © 2005 Wiley-Liss, Inc. [source] Fjx1: A notch-inducible secreted ligand with specific binding sites in developing mouse embryos and adult brainDEVELOPMENTAL DYNAMICS, Issue 3 2005Rebecca Rock Abstract The mouse fjx1 gene was identified as a homologue to the Drosophila gene four-jointed (fj). Fj encodes a transmembrane type II glycoprotein that is partially secreted. The gene was found to be a downstream target of the Notch signaling pathway in leg segmentation and planar cell polarity processes during eye development of Drosophila. Here, we show that fjx1 is not only conserved in vertebrates, but we also identified the murine fjx1 gene as a direct target of Notch signaling. In addition to the previously described expression of fjx1 in mouse brain, we show here that fjx1 is expressed in the peripheral nervous system, epithelial cells of multiple organs, and during limb development. The protein is processed and secreted as a presumptive ligand. Through the use of an fjx1-AP fusion protein, we could visualize fjx1 binding sites at complementary locations, supporting the notion that fjx1 may function as a novel signaling molecule. Developmental Dynamics 234:602,612, 2005. © 2005 Wiley-Liss, Inc. [source] Neuropathic pain and diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2003Dilip Kapur Abstract Neuropathic pain is a common phenomenon resulting from injury to the central or peripheral nervous system. The means by which diabetes results in nerve injury is unclear but the effect is to cause injury at all levels of the nervous system from the level of the peripheral nerves to the brain. Nerve injury causes pain through a cascade of mechanisms resulting in altered processing of sensory input into the nervous system. This alteration occurs through chemical and anatomical changes in the nervous system that are similar to some of the processes seen in central sensitisation following acute pain. Following nerve injury, neuropathic pain occurs not only when these mechanisms are activated but also when sensitisation is maintained. Other processes occurring in neuropathic pain appear to be a loss of normal inhibitory controls as seen by a reduction in local GABA-ergic and descending monoaminergic influences. There are also important changes mediated via glial cells that can maintain neuropathic pain. Diabetes affects all areas of the nervous system and the contribution of higher levels of the nervous system is often overlooked. Neurophysiological and MRI evidence strongly suggest that these may contribute to the pain of diabetic neuropathy. Psychological dysfunction in diabetic patients is an important factor in increasing the suffering associated with all aspects of the disease, but treatment and control of pain can greatly improve the quality of life. Copyright © 2003 John Wiley & Sons, Ltd. [source] High prevalence of vasomotor reflex impairment in newly diagnosed leprosy patientsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2005X. Illarramendi Abstract Background, Initial nerve damage in leprosy occurs in small myelinated and unmyelinated nerve fibers. Early detection of leprosy in the peripheral nervous system is challenging as extensive nerve damage may take place before clinical signs of leprosy become apparent. Patients and methods, In order to determine the prevalence of, and factors associated with, peripheral autonomic nerve dysfunction in newly diagnosed leprosy patients, 76 Brazilian patients were evaluated prior to treatment. Skin vasomotor reflex was tested by means of laser Doppler velocimetry. Blood perfusion and reflex vasoconstriction following an inspiratory gasp were registered on the second and fifth fingers. Results, Vasomotor reflex was impaired in at least one finger in 33/76 (43%) patients. The fifth fingers were more frequently impaired and suffered more frequent bilateral alterations than the second fingers. Multivariate regression analysis showed that leprosy reaction (adjusted odds ratio = 8·11, 95% confidence interval: 1·4,48·2) was associated with overall impaired vasomotor reflex (average of the four fingers). In addition, palmar erythrocyanosis and an abnormal upper limb sensory score were associated with vasomotor reflex impairment in the second fingers, whereas anti-phenolic glycolipid-I antibodies, ulnar somatic neuropathy and a low finger skin temperature were associated with impairment in the fifth fingers. Conclusions, A high prevalence of peripheral autonomic dysfunction as measured by laser Doppler velocimetry was observed in newly diagnosed leprosy patients, which is clinically evident late in the disease. Autonomic nerve lesion was more frequent than somatic lesions and was strongly related to the immune-inflammatory reaction against M. leprae. [source] The position of the neurologist in neuro-oncology1EUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2002W. Grisold Neuro-oncology is a growing new subspeciality with a strong interdisciplinary character. This position paper explains the role of neurology in the multidisciplinary field of neurosurgeons, radiotherapists and general oncologists, dealing with neuro-oncological patients. The paper delineates the varied spectrum of the field of neuro-oncology which expands from primary brain tumours, to metastatic and non-metastatic effects of systemic cancer on the central and peripheral nervous system, neurotoxicity due to cancer treatment and issues of quality of life. It has been written by the scientific neuro-oncology panel of the European Federation of Neurological Societies (EFNS) to delineate the situation of neuro-oncology in Europe, and facilitate the understanding and implementation of this subspeciality in the future. [source] Olfactory deficits in mice overexpressing human wildtype ,-synucleinEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2008Sheila M. Fleming Abstract Accumulation of ,-synuclein in neurons of the central and peripheral nervous system is a hallmark of sporadic Parkinson's disease (PD) and mutations that increase ,-synuclein levels cause familial PD. Transgenic mice overexpressing ,-synuclein under the Thy1 promoter (Thy1-aSyn) have high levels of ,-synuclein expression throughout the brain but no loss of nigrostriatal dopamine neurons up to 8 months, suggesting that they may be useful to model pre-clinical stages of PD. Olfactory dysfunction often precedes the onset of the cardinal motor symptoms of PD by several years and includes deficits in odor detection, discrimination and identification. In the present study, we measured olfactory function in 3- and 9-month-old male Thy1-aSyn mice with a buried pellet test based on latency to find an exposed or hidden odorant, a block test based on exposure to self and non-self odors, and a habituation/dishabituation test based on exposure to non-social odors. In a separate group of mice, ,-synuclein immunoreactivity was assessed in the olfactory bulb. Compared with wildtype littermates, Thy1-aSyn mice could still detect and habituate to odors but showed olfactory impairments in aspects of all three testing paradigms. Thy1-aSyn mice also displayed proteinase K-resistant ,-synuclein inclusions throughout the olfactory bulb. These data indicate that overexpression of ,-synuclein is sufficient to cause olfactory deficits in mice similar to that observed in patients with PD. Furthermore, the buried pellet and block tests provided sufficient power for the detection of a 50% drug effect, indicating their usefulness for testing novel neuroprotective therapies. [source] Impaired behavioural flexibility and memory in mice lacking GDNF family receptor ,2EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2004Vootele Võikar Abstract The glial cell line-derived neurotrophic factor (GDNF) family receptor GFR,2 is the binding receptor for neurturin (NRTN). The main biological responses of GFR,2 are mediated via the Ret receptor tyrosine kinase, although it may also signal independently of Ret via the neural cell adhesion molecule NCAM. GFR,2 is expressed in many neurons of both the central and peripheral nervous system. Mice lacking GFR,2 receptors do not exhibit any gross defects in the central nervous system structure. However, they display profound deficits in the parasympathetic and enteric nervous system, accompanied by significant reduction in body weight after weaning. Here we present the results of behavioural analysis of the GFR,2-knockout mice. The knockout mice did not differ from wild-type mice in basic tests of motor and exploratory activity. However, differences were established in several memory tasks. The knockout mice were not impaired in the acquisition of spatial escape strategy. However, the deficit in flexibility in establishing a new strategy was revealed during reversal learning with the platform in the opposite quadrant of the pool. Furthermore, the knockout mice displayed significant impairment in contextual fear conditioning and conditioned taste aversion tests of memory. The results suggest that GFR,2 signalling plays a role in the development or maintenance of cognitive abilities that help in solving complex learning tasks. [source] Differential sensitivity of sodium channels from the central and peripheral nervous system to the scorpion toxins Lqh-2 and Lqh-3EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002Haijun Chen Abstract The scorpion ,-toxins Lqh-2 and Lqh-3, isolated from the venom of the Israeli yellow scorpion Leiurus quinquestriatus hebraeus, were previously shown to be very potent in removing fast inactivation of rat skeletal muscle sodium channels (Chen et al., 2000). Here, we show that tetrodotoxin-sensitive neuronal channels NaV1.2 and NaV1.7, which are mainly expressed in mammalian central and peripheral nervous systems, respectively, are differentially sensitive to these two toxins. rNaV1.2 and hNaV1.7 channels were studied with patch-clamp methods upon expression in mammalian cells. While Lqh-3 was about 100-times more potent in removing inactivation in hNaV1.7 channels compared with rNaV1.2, Lqh-2 was about 20-times more active in the other direction. Site-directed mutagenesis showed that the differences in the putative binding sites for these toxins, the S3-4 linkers of domain 4, are of major importance for Lqh-3, but not for Lqh-2. [source] Migration of cells into and out of peripheral nerve isografts in the peripheral and central nervous systems of the adult mouseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2001Natalie A. Symons Abstract Peripheral nerve (PN) isografts provide a favourable environment for axon regeneration after peripheral and central nervous system (CNS) injury, but definitive information on the extent of cellular intermixing between donor and host tissues is lacking. We wished to compare migration patterns in fresh and predegenerate PN grafts, and also compare the extent of cell migration after transplantation to peripheral nervous system (PNS) versus CNS. To discern how host and donor cells interact after PN transplantation, sciatic nerve segments were transplanted from inbred adult mice into PN defects (PN,PN grafts) or into lesioned cerebral cortex of opposite gender siblings. Migrating male cells were identified using a Y-chromosome-specific probe and in situ hybridization methods, and characterized immunohistochemically. The extent of donor and host cellular intermixing was similar in fresh and predegenerate PN,PN isografts. There was substantial intermixing of donor and host cells by 8 days. Many host cells migrating into epineurial regions of grafts were immunopositive for F4/80 (macrophages). The endoneurium of grafted PN was also colonized by host cells; some were F4/80+ but many were immunostained with S-100 (Schwann cell marker). Donor S-100+ Schwann cells rapidly migrated out into proximal and distal host PN and by 12 weeks were found at least 2 mm from the grafts. Endoneurial microvessels in grafts were mostly donor-derived. By comparison, in male PN grafts to female CNS, even after 6 weeks few donor cells had migrated out into surrounding host cortex, despite the observation that almost all grafts contained regenerating axons and were thus attached to host CNS tissue. [source] Epidermal keratinocytes as the forefront of the sensory systemEXPERIMENTAL DERMATOLOGY, Issue 3 2007Mitsuhiro Denda Abstract, Various sensors that respond to physical or chemical environmental factors have been identified in the peripheral nervous system. Some of them, which respond to mechanical stress, osmotic pressure, temperature and chemical stimuli (such as pH), are also expressed in epidermal keratinocytes. Neurotransmitters and their receptors, as well as receptors that regulate the neuroendocrine system of the skin, are also present in keratinocytes. Thus, broadly speaking, epidermal keratinocytes appear to be equipped with sensing systems similar to those of the peripheral and central nervous systems. It had long been considered that only nerve C-terminals in the epidermis play a role in skin surface perception. However, building on earlier work on skin receptors and new findings introduced here, we present in this review a novel hypothesis of skin sensory perception, i.e. first, keratinocytes recognize various environmental factors, and then the information is processed and conveyed to the nervous system. [source] Stimulation of keratinocyte differentiation , a new role for the vanilloid receptor subtype 1 (VR1/TRPV1)?EXPERIMENTAL DERMATOLOGY, Issue 2 2005Sonja Ständer Vanilloids and endogenous cannabinoids mediate their actions via the vanilloid receptor subtype 1 (VR1/TRPV1), a non-selective cation channel, which is widely distributed in the central and peripheral nervous system. Only recently, VR1 has been shown to be expressed in keratinocytes in vitro and in vivo. However, a precise description of VR1 localization in epithelial cells was missing. To determine this, we investigated VR1-immunoreactivity as well as mRNA and protein expression in a series of biopsies from normal, diseased, and capsaicin-treated human skin. VR1 was found in epidermal keratinocytes, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands upon immunohistochemistry, RT-PCR and Western blot analysis. Interestingly, in diseased skin such as prurigo nodularis, psoriasis vulgaris, and atopic dermatitis, VR1 expression in keratinocytes correlated with the degree of epidermal differentiation. Enhanced VR1 immunoreactivity and protein content was found in prurigo nodularis in which epidermal keratinocytes are highly differentiated. Under effective capsaicin therapy of prurigo nodularis, the epidermis thinned and the distribution pattern of VR1 on epidermal keratinocytes normalized. In psoriasis vulgaris, a disease with disturbed epidermal differentiation, less intense immunostaining for VR1 was observed. This could be confirmed by western blot analysis showing less VR1 protein amount in comparison to prurigo nodularis although histologically both showed a thickened epidermis. In atopic dermatitis, which is characterized by a moderate epidermal hyperplasia only and regular differentiated keratinocytes, VR1 immunoreactivity was unchanged in comparison to normal skin. These findings suggest that VR1 may contribute to regular differentiation of keratinocytes. VR1 activation opens non-selective cation channels with high permeability to calcium, a ion that is crucially important for the synthesis of cornification proteins such as involucrin, fillagrin and loricrin. The role of VR1 in other epithelial cells of appendage structures remains to be determined. In summary, VR1 is widely distributed in the skin suggesting a central role for this receptor not only in nociception but also maturation and function of epithelial cells. [source] Monitoring of the internalization of neuropeptide Y on neuroblastoma cell line SK-N-MCFEBS JOURNAL, Issue 17 2000Marlies Fabry Neuropeptide Y (NPY) is an important neuromodulator in the central and peripheral nervous system. The peptide acts through different NPY receptor subtypes (Y1,Y5, y6) that belong to the family of G protein-coupled receptors. In general, cellular responses to prolonged exposure to agonists of G protein-coupled receptors are attenuated, often through internalization of the receptors and their bound ligands. In this study, a fluorescent labeled NPY derivative was synthesized and characterized to investigate the internalization of NPY in the human neuroblastoma cell line SK-N-MC. Internalization was proven by binding experiments and subsequent acidic washing as well as by direct visualization by means of confocal laser scanning microscopy. Approximately 20,30% of the fluorescent labeled NPY and a tritium-marked NPY were resistant to acid removal of cell surface-bound ligands indicating internalization. Extracellular fluorescent labeled NPY was found to be distributed heterogeneously in a clustered pattern, which suggests that the ligand-receptor complex is collected in pits and caveolae followed by endocytosis. [source] Matrix metalloproteinase-2 is involved in myelination of dorsal root ganglia neuronsGLIA, Issue 5 2009Helmar C. Lehmann Abstract Matrix metalloproteinases (MMPs) comprise a large family of endopeptidases that are capable of degrading all extracellular matrix components. There is increasing evidence that MMPs are not only involved in tissue destruction but may also exert beneficial effects during axonal regeneration and nerve remyelination. Here, we provide evidence that MMP-2 (gelatinase A) is associated with the physiological process of myelination in the peripheral nervous system (PNS). In a myelinating co-culture model of Schwann cells and dorsal root ganglia neurons, MMP-2 expression correlated with the degree of myelination as determined by immunocytochemistry, zymography, and immunosorbent assay. Modulation of MMP-2 activity by chemical inhibitors led to incomplete and aberrant myelin formation. In vivo MMP-2 expression was detected in the cerebrospinal fluid (CSF) of patients with Guillain-Barré syndrome as well as in CSF and sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy. Our findings suggest an important, previously unrecognized role for MMP-2 during myelination in the PNS. Endogenous or exogenous modulation of MMP-2 activity may be a relevant target to enhance regeneration in demyelinating diseases of the PNS. © 2008 Wiley-Liss, Inc. [source] Development of the Schwann cell lineage: From the neural crest to the myelinated nerveGLIA, Issue 14 2008Ashwin Woodhoo Abstract The myelinating and nonmyelinating Schwann cells in peripheral nerves are derived from the neural crest, which is a transient and multipotent embryonic structure that also generates the other main glial subtypes of the peripheral nervous system (PNS). Schwann cell development occurs through a series of transitional embryonic and postnatal phases, which are tightly regulated by a number of signals. During the early embryonic phases, neural crest cells are specified to give rise to Schwann cell precursors, which represent the first transitional stage in the Schwann cell lineage, and these then generate the immature Schwann cells. At birth, the immature Schwann cells differentiate into either the myelinating or nonmyelinating Schwann cells that populate the mature nerve trunks. In this review, we will discuss the biology of the transitional stages in embryonic and early postnatal Schwann cell development, including the phenotypic differences between them and the recently identified signaling pathways, which control their differentiation and maintenance. In addition, the role and importance of the microenvironment in which glial differentiation takes place will be discussed. © 2008 Wiley-Liss, Inc. [source] Myelin-phagocytosing macrophages in isolated sciatic and optic nerves reveal a unique reactive phenotypeGLIA, Issue 3 2008Denise van Rossum Abstract Macrophages are key effectors in demyelinating diseases of the central and peripheral nervous system by phagocytosing myelin and releasing immunoregulatory mediators. Here, we report on a distinct, a priori anti-inflammatory reaction of macrophages phagocytosing myelin upon contact with damaged nerve tissue. Macrophages rapidly invaded peripheral (sciatic) and central (optic) nerve tissues in vitro, readily incorporated myelin and expressed high levels of phagocytosis-associated molecules (e.g., Fc and scavenger receptors). In contrast, factors involved in antigen presentation (MHC class-II, CD80, CD86) revealed only a restricted expression. In parallel, a highly ordered appearance of cytokines and chemokines was detected. IL-10, IL-6, CCL22, and CXCL1 were immediately but transiently induced, whereas CCL2, CCL11, and TGF, revealed more persisting levels. Such a profile would attract neutrophils, monocytes/macrophages, and Th2 cells as well as bias for a Th2-supporting environment. Importantly, proinflammatory/Th1-supporting factors, such as TNF,, IL-12p70, CCL3, and CCL5, were not induced. Still the simultaneous presence of TGF, and IL-6 could assist Th17 development, further depending on yet not present IL-23. The release pattern was clearly distinct from reactive phenotypes induced in isolated macrophages and microglia upon treatment with IL-4, IL-13, bacterial lipopolysaccharide, IFN,, or purified myelin. Nerve-exposed macrophages thus commit to a unique functional orientation. © 2007 Wiley-Liss, Inc. [source] A mouse embryonic stem cell model of Schwann cell differentiation for studies of the role of neurofibromatosis type 1 in Schwann cell development and tumor formationGLIA, Issue 11 2007Therese M. Roth Abstract The neurofibromatosis Type 1 (NF1) gene functions as a tumor suppressor gene. One known function of neurofibromin, the NF1 protein product, is to accelerate the slow intrinsic GTPase activity of Ras to increase the production of inactive rasGDP, with wide-ranging effects on p21ras pathways. Loss of neurofibromin in the autosomal dominant disorder NF1 is associated with tumors of the peripheral nervous system, particularly neurofibromas, benign lesions in which the major affected cell type is the Schwann cell (SC). NF1 is the most common cancer predisposition syndrome affecting the nervous system. We have developed an in vitro system for differentiating mouse embryonic stem cells (mESC) that are NF1 wild type (+/+), heterozygous (+/,), or null (,/,) into SC-like cells to study the role of NF1 in SC development and tumor formation. These mES-generated SC-like cells, regardless of their NF1 status, express SC markers correlated with their stage of maturation, including myelin proteins. They also support and preferentially direct neurite outgrowth from primary neurons. NF1 null and heterozygous SC-like cells proliferate at an accelerated rate compared to NF1 wild type; this growth advantage can be reverted to wild type levels using an inhibitor of MAP kinase kinase (Mek). The mESC of all NF1 types can also be differentiated into neuron-like cells. This novel model system provides an ideal paradigm for studies of the role of NF1 in cell growth and differentiation of the different cell types affected by NF1 in cells with differing levels of neurofibromin that are neither transformed nor malignant. © 2007 Wiley-Liss, Inc. [source] Nodal protrusions, increased Schmidt-Lanterman incisures, and paranodal disorganization are characteristic features of sulfatide-deficient peripheral nervesGLIA, Issue 6 2007Tomiko Hoshi Abstract Galactocerebroside and sulfatide are two major glycolipids in myelin; however, their independent functions are not fully understood. The absence of these glycolipids causes disruption of paranodal junctions, which separate voltage-gated Na+ and Shaker -type K+ channels in the node and juxtaparanode, respectively. In contrast to glial cells in the central nervous system (CNS), myelinating Schwann cells in the peripheral nervous system (PNS) possess characteristic structures, including microvilli and Schmidt-Lanterman incisures, in addition to paranodal loops. All of these regions are involved in axo,glial interactions. In the present study, we examined cerebroside sulfotransferase-deficient mice to determine whether sulfatide is essential for axo,glial interactions in these PNS regions. Interestingly, marked axonal protrusions were observed in some of the nodal segments, which often contained abnormally enlarged vesicles, like degenerated mitochondria. Moreover, many transversely cut ends of microvilli surrounded the mutant nodes, suggesting that alignments of the microvilli were disordered. The mutant PNS showed mild elongation of nodal Na+ channel clusters. Even though Caspr and NF155 were completely absent in half of the paranodes, short clusters of these molecules remained in the rest of the paranodal regions. Ultrastructural analysis indicated the presence of transverse bands in some paranodal regions and detachment of the outermost several loops. Furthermore, the numbers of incisures were remarkably increased in the mutant internode. Therefore, these results indicate that sulfatide may play an important role in the PNS, especially in the regions where myelin,axon interactions occur. © 2007 Wiley-Liss, Inc. [source] Calponin is expressed by fibroblasts and meningeal cells but not olfactory ensheathing cells in the adult peripheral olfactory systemGLIA, Issue 2 2007Chrystelle Ibanez Abstract Olfactory ensheathing cells (OECs), the principal glial cells of the peripheral olfactory system, have many phenotypic similarities with Schwann cells of the peripheral nervous system. This makes reliably distinguishing these two cells types difficult, especially following transplantation into areas of injury in the central nervous system. In an attempt to identify markers by which these two cells types can be distinguished, a recent proteomic analysis of fetal OECs and adult Schwann cells identified the actin-binding protein calponin as a potential marker expressed by OECs but not Schwann cells. Since many studies designed with the translational goal of autologous transplantation in mind have used adult OECs, this study examined the expression of calponin by adult OECs, both in vivo within the peripheral olfactory system and in vitro. Calponin colocalized with strongly fibronectin positive fibroblasts in the olfactory mucosa (OM) and meningeal cells in the olfactory bulb (OB) but not with S100, or neuropeptide-Y positive OECs. In tissue culture, calponin was strongly expressed by fibronectin-expressing fibroblasts from OM, sciatic nerve and skin and by meningeal cells from the OB, but not by p75NTR - and S100,-expressing OECs. These data, supported by Western blotting, indicate that calponin can not be used to distinguish adult OECs and Schwann cells. © 2006 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||