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Peripherial nervous system

Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
Regulatory T cells (Tregs) are necessary for the maintenance of immune tolerance. Tregs are divided into two major populations: one is thymus derived and the other develops in the periphery. Among these Tregs, CD4+ CD25+ Tregs, which mainly originate in the thymus, have been extensively studied. Transcription factor Foxp3 is well known as a master regulatory gene for the development and function of CD4+ CD25+ Tregs. On the other hand, peripheral Tregs consist of distinct cell subsets including Foxp3-dependent extrathymically developed Tregs and interleukin (IL)-10-producing type I regulatory T (Tr1) cells...
2018: Frontiers in Immunology
Nicolas Diotel, Thierry D Charlier, Christian Lefebvre d'Hellencourt, David Couret, Vance L Trudeau, Joel C Nicolau, Olivier Meilhac, Olivier Kah, Elisabeth Pellegrini
Sex steroid hormones are synthesized from cholesterol and exert pleiotropic effects notably in the central nervous system. Pioneering studies from Baulieu and colleagues have suggested that steroids are also locally-synthesized in the brain. Such steroids, called neurosteroids, can rapidly modulate neuronal excitability and functions, brain plasticity, and behavior. Accumulating data obtained on a wide variety of species demonstrate that neurosteroidogenesis is an evolutionary conserved feature across fish, birds, and mammals...
2018: Frontiers in Neuroscience
Renan Aguilar-Valenzuela, Jason Netland, Young-Jin Seo, Michael J Bevan, Arash Grakoui, Mehul S Suthar
The mouse model of West Nile virus, which is a leading cause of mosquito-borne encephalitis worldwide, has provided fundamental insights into the host and viral factors that regulate viral pathogenesis and infection outcome. In particular, CD8+ T cells are critical for controlling WNV replication and promoting protection against infection. Here, we present the characterization of a T cell receptor (TCR) transgenic mouse with specificity to the immunodominant epitope in the WNV NS4B protein (herein referred to as transgenic WNV-I mice)...
March 7, 2018: Journal of Virology
Rebecca K Sheean, Fiona C McKay, Erika Cretney, Christopher R Bye, Nirma D Perera, Doris Tomas, Richard A Weston, Karlene J Scheller, Elvan Djouma, Parvathi Menon, Stephen D Schibeci, Najwa Marmash, Justin J Yerbury, Stephen L Nutt, David R Booth, Graeme J Stewart, Mathew C Kiernan, Steve Vucic, Bradley J Turner
Importance: Neuroinflammation appears to be a key modulator of disease progression in amyotrophic lateral sclerosis (ALS) and thereby a promising therapeutic target. The CD4+Foxp3+ regulatory T-cells (Tregs) infiltrating into the central nervous system suppress neuroinflammation and promote the activation of neuroprotective microglia in mouse models of ALS. To our knowledge, the therapeutic association of host Treg expansion with ALS progression has not been studied in vivo. Objective: To assess the role of Tregs in regulating the pathophysiology of ALS in humans and the therapeutic outcome of increasing Treg activity in a mouse model of the disease...
March 5, 2018: JAMA Neurology
Chih-Chun J Lin, Isaiah A A Neve, Meng C Wang
Aging is fundamental to life and reflects functional declines in different tissues at the organismal level. As a systematic process, aging can be influenced by the interplay between genetic and environmental factors, and the nervous system plays a crucial role in this regulation. Environmental inputs can be sensed by the nervous system, which consequently triggers signaling outputs toward peripheral tissues to regulate gene expression systematically. Thus, understanding the underlying molecular mechanisms behind environmentally triggered neuron-periphery cross-talk is crucial for the promotion of an organism's health and longevity...
February 1, 2018: Genes & Development
Mahsa Sadeghi, Andelain Erickson, Joel Castro, Annemie Deiteren, Andrea M Harrington, Luke Grundy, David J Adams, Stuart M Brierley
Irritable bowel syndrome and inflammatory bowel disease are major forms of chronic visceral pain, which affect over 15% of the global population. In order to identify new therapies, it is important to understand the underlying causes of chronic visceral pain. This review provides recent evidence demonstrating that inflammation or infection of the gastrointestinal tract triggers specific changes in the neuronal excitability of sensory pathways responsible for the transmission of nociceptive information from the periphery to the central nervous system...
February 22, 2018: International Journal of Biochemistry & Cell Biology
Jennifer Blaze, Jun Wang, Lap Ho, Natalia Mendelev, Fatemeh Haghighi, Giulio Maria Pasinetti
SCOPE: Stress is a known contributor to various forms of disease in humans and animals, although mechanisms are still unknown. In animals, psychosocial stress-induced depression/anxiety phenotypes are coincidental with increased inflammation in both brain and blood. We recently showed that a novel treatment with a select bioactive polyphenol preparation promotes resilience to stress-mediated depression/anxiety phenotypes mice. Moreover, we identified selective bioactive phenolic compounds within the polyphenol preparation that were effective in mitigating the behavioral effects of bone marrow transplantation from stressed mice...
February 22, 2018: Molecular Nutrition & Food Research
J Dai, L-J Xu, G-D Han, H-L Sun, G-T Zhu, H-T Jiang, G-Y Yu, X-M Tang
OBJECTIVE: Spinal cord injury (SCI) is a severe trauma to the central nervous system. Long non-coding RNAs have been reported to play essential roles in spinal cord injury. This study mainly explored the role of micro-125 in the regulation of spinal cord injury by regulating STAT3. MATERIALS AND METHODS: The stable mouse model of cervical spinal cord contusion was established by Infinite Horizon spinal cord striker, and the model mice' motor function was analyzed...
February 2018: European Review for Medical and Pharmacological Sciences
Otto Muzik, Kaice T Reilly, Vaibhav A Diwadkar
The defense of body temperature against environmental thermal challenges is a core objective of homeostatic regulation governed by the autonomic nervous system. Autonomous mechanisms of thermoregulation are only weakly affected by top-down modulation, allowing only transient tolerance for extreme cold. There is however, anecdotal evidence of a unique set of individuals known for extreme cold tolerance. Here we present a case study of a 57-year old Dutch national, Wim Hof, the so-called "Iceman", with the ability to withstand frequent prolonged periods of extreme cold exposure based on the practice of a self-developed technique involving a combination of forced breathing, cold exposure and meditation (collectively referred to as the Wim Hof Method, henceforth "WHM")...
February 10, 2018: NeuroImage
Karl Alexander Iwen, Rebecca Ölkrug, Georg Brabant
Thyroid hormones (TH) are of central importance for thermogenesis, energy homeostasis, and metabolism. Here we will discuss these aspects by focussing on the physiological aspects of TH-dependent regulation in response to cold exposure and fasting which will be compared to alterations in primary hyper- and hypothyroidism. In particular, we will summarise current knowledge on regional thyroid hormone status in the central nervous system (CNS) and in peripheral cells. In contrast to hyper- and hypothyroidism, where parallel changes are observed, local alterations in the CNS differ to peripheral compartments when induced by cold exposure or fasting...
February 6, 2018: Journal of Molecular Endocrinology
Tatyana Veremeyko, Amanda W Y Yung, Marina Dukhinova, Inna S Kuznetsova, Igor Pomytkin, Alexey Lyundup, Tatyana Strekalova, Natasha S Barteneva, Eugene D Ponomarev
Although it has been demonstrated that cAMP pathway affect both adaptive and innate cell functions, the role of this pathway in the regulation of T-cell-mediated central nervous system (CNS) autoimmune inflammation, such as in experimental autoimmune encephalomyelitis (EAE), remains unclear. It is also unclear how cAMP pathway affects the function of CD4 T cells in vivo at the site of inflammation. We found that adenylyl cyclase activator Forskolin besides inhibition of functions autoimmune CD4 T cells also upregulated microRNA (miR)-124 in the CNS during EAE, which is associated with M2 phenotype of microglia/macrophages...
2018: Frontiers in Immunology
Ilia D Vainchtein, Gregory Chin, Frances S Cho, Kevin W Kelley, John G Miller, Elliott C Chien, Shane A Liddelow, Phi T Nguyen, Hiromi Nakao-Inoue, Leah C Dorman, Omar Akil, Satoru Joshita, Ben A Barres, Jeanne T Paz, Ari B Molofsky, Anna V Molofsky
Neuronal synapse formation and remodeling is essential to central nervous system (CNS) development and is dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this impacts CNS synapses is largely unknown. Here, we show that the IL-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo...
February 1, 2018: Science
Alex James Clark, Guillermo Menendez, Mona AlQatari, Niral Patel, Erik Arstad, Giampietro Schiavo, Martin Koltzenburg
Primary afferent sensory neurons are incredibly long cells, often traversing distances of over one metre in humans. Cutaneous sensory stimuli are transduced in the periphery by specialised end-organs or free nerve endings which code the stimulus into electrical action potentials that propagate towards the central nervous system.Despite significant advances in our knowledge of sensory neuron physiology and ion channel expression, many commonly used techniques fail to accurately model the primary afferent neuron in its entirety...
February 6, 2018: Pain
Paul C Guest
Many diseases result from programming effects in utero. This chapter describes recent advances in proteomic studies which have improved our understanding of the underlying pathophysiological pathways in the major psychiatric disorders, resulting in the development of potential novel biomarker tests. Such tests should be based on measurement of blood-based proteins given the ease of accessibility of this medium and the known connections between the periphery and the central nervous system. Most importantly, emerging biomarker tests should be developed on lab-on-a-chip and other handheld devices to enable point-of-care use...
2018: Methods in Molecular Biology
Tim Regan, Andrew C Gill, Sara M Clohisey, Mark W Barnett, Carmine M Pariante, Neil A Harrison, David A Hume, Edward T Bullmore, Tom C Freeman
Several lines of evidence link macrophage activation and inflammation with (monoaminergic) nervous systems in the etiology of depression. IFN treatment is associated with depressive symptoms, whereas anti-TNFα therapies elicit positive mood. This study describes the actions of 2 monoaminergic antidepressants (escitalopram, nortriptyline) and 3 anti-inflammatory drugs (indomethacin, prednisolone, and anti-TNFα antibody) on the response of human monocyte-derived macrophages (MDMs) from 6 individuals to LPS or IFN-α...
January 26, 2018: Journal of Leukocyte Biology
Mahendra Pratap Kashyap, Callie Roberts, Mohammad Waseem, Pradeep Tyagi
Neurotrophins are a family of proteins that play an important role in the regulation of the growth, survival, and differentiation of neurons in the central and peripheral nervous system. Neurotrophins were earlier characterized by their role in early development, growth, maintenance, and the plasticity of the nervous system during development, but recent findings also indicate their complex role during normal physiology in both neuronal and non-neuronal tissues. Therefore, it is important to recognize a deficiency in the expression of neurotrophins, a major factor driving the debilitating features of several neurologic and psychiatric diseases/disorders...
January 25, 2018: Molecular Neurobiology
Claudia Rivetti, Bruno Campos, Benjamín Piña, Demetrio Raldúa, Yasuhiko Kato, Hajime Watanabe, Carlos Barata
Tryptophan hydroxylase (TRH) is the rate limiting enzyme in the serotonin synthesis. CRISPR-Cas9 technology was used to generate seven indel TRH mutants in Daphnia magna. Mono-allelic indel TRH-/+ clones showed normal levels of serotonin, measured by both immunohistochemistry and mass spectrometry (LC-MS/MS), whereas bi-allelic indel TRH-/- clones showed no detectable levels of serotonin. Life history and behavioral responses of TRH-/- clones showed the anti-phenotype of those exposed to selective serotonin reuptake inhibitors (SSRI)...
January 24, 2018: Scientific Reports
Tao Wang, Olivia Hurwitz, Steven G Shimada, Daofeng Tian, Feng Dai, Jiangbing Zhou, Chao Ma, Robert H LaMotte
Bupivacaine is a commonly used local anesthetic in postoperative pain management. We evaluated the effects of a prolonged, local delivery of bupivacaine on pain behavior accompanying a chronic compression of the dorsal root ganglion (CCD) - an animal model of radicular pain. Poly(lactide-coglycolide) (PLGA) nanoparticles encapsulating bupivacaine were injected unilaterally into the L3 and L4 DRGs of mice just before producing CCD by implanting a stainless-steel rod in the intervertebral foramen of each ganglion...
January 17, 2018: Neuroscience Letters
Chelsea M Griffith, Tore Eid, Gregory M Rose, Peter R Patrylo
Epidemiological data have shown that metabolic disease can increase the propensity for developing cognitive decline and dementia, particularly Alzheimer's disease (AD). While this interaction is not completely understood, clinical studies suggest that both hyper- and hypoinsulinemia are associated with an increased risk for developing AD. Indeed, insulin signaling is altered in post-mortem brain tissue from AD patients and treatments known to enhance insulin signaling, can improve cognitive function. Further, clinical evidence has shown that AD patients and mouse models of AD often display alterations in peripheral metabolism...
January 15, 2018: Neuropharmacology
Fredric P Manfredsson, Kelvin C Luk, Matthew J Benskey, Aysegul Guezer, Joanna Garcia, Nathan C Kuhn, Ivette M Sandoval, Joseph R Patterson, Alana O'Mara, Reid Yonkers, Jeffrey H Kordower
Alpha-Synuclein (α-syn) is by far the most highly vetted pathogenic and therapeutic target in Parkinson's disease. Aggregated α-syn is present in sporadic Parkinson's disease, both in the central nervous system (CNS) and peripheral nervous system (PNS). The enteric division of the PNS is of particular interest because 1) gastric dysfunction is a key clinical manifestation of Parkinson's disease, and 2) Lewy pathology in myenteric and submucosal neurons of the enteric nervous system (ENS) has been referred to as stage zero in the Braak pathological staging of Parkinson's disease...
January 13, 2018: Neurobiology of Disease
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