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Peripherial nervous system

Joanna Kisała, Kinga I Heclik, Krzysztof Pogocki, Dariusz Pogocki
The blood-brain barrier (BBB) is a complex system controlling two-way substances traffic between circulatory (cardiovascular) system and central nervous system (CNS). It is almost perfectly crafted to regulate brain homeostasis and to permit selective transport of molecules that are essential for brain function. For potential drug candidates, the CNS-oriented neuropharmaceuticals as well as for those of primary targets in the periphery, the extent to which a substance in the circulation gains access to the CNS seems crucial...
May 16, 2018: Current Medicinal Chemistry
Mariah L Hoye, Angela S Archambault, Taylor M Gordon, Landon K Oetjen, Matthew D Cain, Robyn S Klein, Seth D Crosby, Brian S Kim, Timothy M Miller, Gregory F Wu
Innate immune cells are integral to the pathogenesis of several diseases of the central nervous system (CNS), including multiple sclerosis (MS). Dendritic cells (DCs) are potent CD11c+ antigen-presenting cells that are critical regulators of adaptive immune responses, particularly in autoimmune diseases such as MS. The regulation of DC function in both the periphery and CNS compartment has not been fully elucidated. One limitation to studying the role of CD11c+ DCs in the CNS is that microglia can upregulate CD11c during inflammation, making it challenging to distinguish bone marrow-derived DCs (BMDCs) from microglia...
May 10, 2018: Immunology
A Trost, C Runge, D Bruckner, A Kaser-Eichberger, B Bogner, C Strohmaier, H A Reitsamer, F Schroedl
Tissues of the central nervous system (CNS), including the optic nerve (ON), are considered a-lymphatic. However, lymphatic structures have been described in the dura mater of human ON sheaths. Since it is known that lymphatic markers are also expressed by single non-lymphatic cells, these results need confirmation according to the consensus statement for the use of lymphatic markers in ophthalmologic research. The aim of this study was to screen for the presence of lymphatic structures in the adult human ON using a combination of four lymphatic markers...
May 7, 2018: Experimental Eye Research
Alex Kalyuzhny
Two processes are known to take place during neuroinflammation: (i) resident immune cells are activated and (ii) inflammatory leukocytes in the periphery begin to infiltrate the central nervous system (CNS).[…].
May 8, 2018: Cells
Rejane Rua, Dorian B McGavern
The central nervous system (CNS) is an immunologically specialized tissue protected by a blood-brain barrier. The CNS parenchyma is enveloped by a series of overlapping membranes that are collectively referred to as the meninges. The meninges provide an additional CNS barrier, harbor a diverse array of resident immune cells, and serve as a crucial interface with the periphery. Recent studies have significantly advanced our understanding of meningeal immunity, demonstrating how a complex immune landscape influences CNS functions under steady-state and inflammatory conditions...
May 3, 2018: Trends in Molecular Medicine
Allan Barrea, Benoit P Delhaye, Philippe Lefèvre, Jean-Louis Thonnard
During tactile exploration, partial slips occur systematically at the periphery of fingertip-object contact prior to full slip. Although the mechanics of partial slips are well characterized, the perception of such events is unclear. Here, we performed psychophysical experiments to assess partial slip detection ability on smooth transparent surfaces. In these experiments, the index fingertip of human subjects was stroked passively by a smooth, transparent glass plate while we imaged the contact slipping against the glass...
May 4, 2018: Scientific Reports
Xintong Dong, Xinzhong Dong
Itch is a unique sensory experience that is encoded by genetically distinguishable neurons both in the peripheral nervous system (PNS) and central nervous system (CNS) to elicit a characteristic behavioral response (scratching). Itch interacts with the other sensory modalities at multiple locations, from its initiation in a particular dermatome to its transmission to the brain where it is finally perceived. In this review, we summarize the current understanding of the molecular and neural mechanisms of itch by starting in the periphery, where itch is initiated, and discussing the circuits involved in itch processing in the CNS...
May 2, 2018: Neuron
Tyler J Wildes, Adam Grippin, Kyle A Dyson, Brandon M Wummer, David J Damiani, Rebecca S Abraham, Catherine Flores, Duane A Mitchell
PURPOSE: Adoptive T cell immunotherapy (ACT) has emerged as a viable therapeutic for peripheral and central nervous system (CNS) tumors. In peripheral cancers, optimal efficacy of ACT is reliant on dendritic cells (DCs) in the tumor microenvironment. However, the CNS is largely devoid of resident migratory DCs to function as antigen-presenting cells during immunotherapy. Herein, we demonstrate that cellular interactions between adoptively-transferred tumor-reactive T cells and bone marrow-derived HSPCs lead to the generation of potent intratumoral DCs within the CNS compartment...
April 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Christoforos Tsantoulas, Franziska Denk, Massimo Signore, Mohammed A Nassar, Kensuke Futai, Stephen B McMahon
Voltage-gated potassium (Kv) channels are increasingly recognised as key regulators of nociceptive excitability. Kcns1 is one of the first potassium channels to be associated with neuronal hyperexcitability and mechanical sensitivity in the rat, as well as pain intensity and risk of developing chronic pain in humans. Here, we show that in mice Kcns1 is predominantly expressed in the cell body and axons of myelinated sensory neurons positive for neurofilament-200, including Aδ-fiber nociceptors and low-threshold Aβ mechanoreceptors...
April 24, 2018: Pain
Wei-Na Jin, Rayna Gonzales, Yan Feng, Kristofer Wood, Zhi Chai, Jing-Fei Dong, Antonio La Cava, Fu-Dong Shi, Qiang Liu
BACKGROUND AND PURPOSE: Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury. METHODS: Using a mouse strain that harbors a transgenic T-cell receptor to a central nervous system antigen, MOG35-55 (myelin oligodendrocyte glycoprotein) epitope (2D2), we determined the anatomic location and involvement of antigen-presenting cells in the development of T-cell reactivity after brain ischemia and how T-cell reactivity impacts stroke outcome...
April 25, 2018: Stroke; a Journal of Cerebral Circulation
Tatsuya Ishikawa, Kei Eto, Sun Kwang Kim, Hiroaki Wake, Ikuko Takeda, Hiroshi Horiuchi, Andrew J Moorhouse, Hitoshi Ishibashi, Junichi Nabekura
Peripheral nerve injury causes maladaptive plasticity in the central nervous system and induces chronic pain. In addition to the injured limb, abnormal pain sensation can appear in the limb contralateral to the injury, called mirror image pain. Since synaptic remodeling in the primary somatosensory cortex (S1) has critical roles in the induction of chronic pain, cortical reorganization in the S1 ipsilateral to the injured limb may also accompany mirror image pain. To elucidate this, we conducted in vivo two-photon calcium imaging of neuron and astrocyte activity in the ipsilateral S1 following a peripheral nerve injury...
April 16, 2018: Pain
Martine Gehin, Richard W D Welford, Marco Garzotti, Magali Vercauteren, Peter M A Groenen, Oliver Nayler, Patricia N Sidharta, Jasper Dingemanse
Serotonin (5-HT) is synthesized from dietary tryptophan (Trp) and plays an important role in numerous diseases of the central nervous system and periphery. Stable isotope tracers enable safe monitoring of metabolic rates. Here we demonstrate measurement of peripheral 5-HT synthesis in healthy subjects by monitoring the produced [13 C10 ]-5-HT (h-5-HT) in EDTA-whole blood from 3 doses of orally administered [13 C11 ]-Trp (h-Trp) tracer. h-Trp was rapidly absorbed and distributed in a multiphasic manner, followed by a slower terminal elimination phase...
April 16, 2018: Clinical Pharmacology and Therapeutics
Rui Li, Amit Bar-Or
Increasing evidence has suggested that both antibody-dependent and antibody-independent functions of B cells are involved in multiple sclerosis (MS). The contrasting results of distinct B-cell targeting therapies in MS patients underscores the importance of elucidating these multiple B-cell functions. In this review, we discuss the generation of autoreactive B cells, migration of B cells into the central nervous system (CNS), and how different functions of B cells may contribute to MS disease activity and potentially mitigation in both the periphery and CNS compartments...
April 16, 2018: Cold Spring Harbor Perspectives in Medicine
Atsushi Takazawa, Naosuke Kamei, Nobuo Adachi, Mitsuo Ochi
Old astrocyte specifically induced substance (OASIS) is an endoplasmic reticulum (ER) stress transducer specifically expressed in astrocytes and osteoblasts. OASIS regulates the differentiation of neural precursor cells into astrocytes in the central nervous system. This study aimed to elucidate the involvement of ER stress responses stimulated via OASIS in astrogliosis following spinal cord injury. In a mouse model of spinal cord contusion injury, OASIS mRNA and protein expression were evaluated at days 7 and 14...
March 2018: Neural Regeneration Research
Chan Lek Tan, Zachary A Knight
The regulation of body temperature is one of the most critical functions of the nervous system. Here we review our current understanding of thermoregulation in mammals. We outline the molecules and cells that measure body temperature in the periphery, the neural pathways that communicate this information to the brain, and the central circuits that coordinate the homeostatic response. We also discuss some of the key unresolved issues in this field, including the following: the role of temperature sensing in the brain, the molecular identity of the warm sensor, the central representation of the labeled line for cold, and the neural substrates of thermoregulatory behavior...
April 4, 2018: Neuron
Adwitia Dey, Joselyn N Allen, James W Fraser, Lindsay M Snyder, Yuan Tian, Limin Zhang, Robert F Paulson, Andrew Patterson, Margherita T Cantorna, Pamela A Hankey-Giblin
Neurodegeneration is a critical problem in aging populations and is characterized by severe central nervous system (CNS) inflammation. Macrophages closely regulate inflammation in the CNS and periphery by taking on different activation states. The source of inflammation in many neurodegenerative diseases has been preliminarily linked to a decrease in the CNS M2 macrophage population and a subsequent increase in M1-mediated neuroinflammation. The Recepteur D'Origine Nantais (Ron) is a receptor tyrosine kinase expressed on tissue-resident macrophages including microglia...
2018: Frontiers in Immunology
Sara Bachiller, María Angustias Roca-Ceballos, Irene García-Domínguez, Eva María Pérez-Villegas, David Martos-Carmona, Miguel Ángel Pérez-Castro, Luis Miguel Real, José Luis Rosa, Lucía Tabares, José Luis Venero, José Ángel Armengol, Ángel Manuel Carrión, Rocío Ruiz
A missense mutation in HERC1 provokes loss of cerebellar Purkinje cells, tremor, and unstable gait in tambaleante (tbl) mice. Recently, we have shown that before cerebellar degeneration takes place, the tbl mouse suffers from a reduction in the number of vesicles available for release at the neuromuscular junction (NMJ). The aim of the present work was to study to which extent the alteration in HERC1 may affect other cells in the nervous system and how this may influence the motor dysfunction observed in these mice...
March 30, 2018: Molecular Neurobiology
Alessandra Berry, Veronica Bellisario, Pamela Panetta, Carla Raggi, Maria C Magnifico, Marzia Arese, Francesca Cirulli
A growing body of evidence suggests the consumption of high-fat diet (HFD) during pregnancy to model maternal obesity and the associated increase in oxidative stress (OS), might act as powerful prenatal stressors, leading to adult stress-related metabolic or behavioral disorders. We hypothesized that administration of antioxidants throughout gestation might counteract the negative effects of prenatal exposure to metabolic challenges (maternal HFD feeding during pregnancy) on the developing fetus. In this study, female C57BL/6J mice were fed HFD for 13 weeks (from 5-weeks of age until delivery) and were exposed to the N-acetyl-cysteine (NAC) antioxidant from 10-weeks of age until right before delivery...
2018: Frontiers in Behavioral Neuroscience
Chunxue Zhou, Suraj B Teegala, Bilal A Khan, Christina Gonzalez, Vanessa H Routh
Hypoglycemia is a profound threat to the brain since glucose is its primary fuel. As a result, glucose sensors are widely located in the central nervous system and periphery. In this perspective we will focus on the role of hypothalamic glucose-inhibited (GI) neurons in sensing and correcting hypoglycemia. In particular, we will discuss GI neurons in the ventromedial hypothalamus (VMH) which express neuronal nitric oxide synthase (nNOS) and in the perifornical hypothalamus (PFH) which express orexin. The ability of VMH nNOS-GI neurons to depolarize in low glucose closely parallels the hormonal response to hypoglycemia which stimulates gluconeogenesis...
2018: Frontiers in Physiology
Kristen A Davenport, Jeffrey R Christiansen, Jifeng Bian, Michael Young, Joseph Gallegos, Sehun Kim, Aru Balachandran, Candace K Mathiason, Edward A Hoover, Glenn C Telling
The prevalence, host range and geographical bounds of chronic wasting disease (CWD), the prion disease of cervids, are expanding. Horizontal transmission likely contributes the majority of new CWD cases, but the mechanism by which prions are transmitted among CWD-affected cervids remains unclear. To address the extent to which prion amplification in peripheral tissues contributes to contagious transmission, we assessed the prion levels in central nervous and lymphoreticular system tissues in white-tailed deer (Odocoileus virginianus), red deer (Cervus elaphus elaphus) and elk (Cervus canadensis)...
March 26, 2018: Journal of General Virology
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