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Peripherial nervous system

Riccardo Dore, Luka Levata, Hendrik Lehnert, Carla Schulz
Nesfatin-1 was identified in 2006 as a potent anorexigenic peptide involved in the regulation of homeostatic feeding. It is processed from the precursor-peptide NEFA/nucleobindin 2 (NUCB2) which is expressed both in the central nervous system as well as in the periphery, from where it can access the brain via non-saturable transmembrane diffusion. In hypothalamus and brainstem, nesfatin-1 recruits the oxytocin-, the melancortin- and other systems to relay its anorexigenic properties. NUCB2/nesfatin-1 peptide expression in reward-related areas suggests that nesfatin-1 might also be involved in hedonic feeding...
October 17, 2016: Journal of Endocrinology
João Casaca-Carreira, Yasin Temel, Iñaki Larrakoetxea, Ali Jahanshahi
Antisense oligonucleotide (AON) therapy is emerging as a potential treatment strategy for neurodegenerative diseases, such as spinal muscular atrophy, Huntington's disease, and amyotrophic lateral sclerosis. AONs function at the cellular level by, for example, direct interference with the expression of gene products or the molecular activation of neuroprotective pathways. However, AON therapy faces a major obstacle limiting its clinical application for central nervous system (CNS) disorders: the blood-brain barrier...
October 18, 2016: Nucleic Acid Therapeutics
Grace O'Neill, Christa Musto, George Gomez
Neuronal development and differentiation is modulated by activity-dependent mechanisms that stimulate endogenous neurogenesis and differentiation to promote adaptive survival of the organism. Studies on bird odor imprinting have shown how sensory stimuli or environmental influences can affect neonatal behavior, presumably by remodeling the developing nervous system. It is unclear whether these changes originate from the sensory neurons themselves or from the brain. Thus, we attempted to address this by using an in vitro system to separate the peripheral neurons from their central connections...
October 7, 2016: Journal of Neuroscience Research
Kirsten S Evonuk, Carson E Moseley, Ryan E Doyle, Casey T Weaver, Tara M DeSilva
A major hallmark of the autoimmune demyelinating disease multiple sclerosis (MS) is immune cell infiltration into the brain and spinal cord resulting in myelin destruction, which not only slows conduction of nerve impulses, but causes axonal injury resulting in motor and cognitive decline. Current treatments for MS focus on attenuating immune cell infiltration into the central nervous system (CNS). These treatments decrease the number of relapses, improving quality of life, but do not completely eliminate relapses so long-term disability is not improved...
2016: Journal of Visualized Experiments: JoVE
Eyal Asor, Dorit Ben-Shachar
It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages. The present article reviews the main theoretical and practical concepts in the research of gene environment interaction, emphasizing the need for models simulating real life complexity. We review a novel approach to study gene environment interaction in which a brief post-natal interference with the expression of multiple genes, by hindering the activity of the ubiquitous transcription factor specificity protein 1 (Sp1) is followed by later-in-life exposure of rats to stress...
September 22, 2016: World Journal of Psychiatry
Amanda K Huber, David A Giles, Benjamin M Segal, David N Irani
Eotaxins are C-C motif chemokines first identified as potent eosinophil chemoattractants. They facilitate eosinophil recruitment to sites of inflammation in response to parasitic infections as well as allergic and autoimmune diseases such as asthma, atopic dermatitis, and inflammatory bowel disease. The eotaxin family currently includes three members: eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26). Despite having only ~30% sequence homology to one another, each was identified based on its ability to bind the chemokine receptor, CCR3...
September 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Weihong Pan, Abba J Kastin
Here we summarize three aspects of our understanding of the interactions of cytokines and neurotrophic peptides/proteins with the blood-brain and blood-spinal cord barriers (BBB): (a) pharmacokinetic analysis that has been reported for native cytokines and neurotrophic peptides/proteins; (b) landmark work on conjugated proteins to enhance their delivery across the normal BBB; and (c) regulatory changes under pathophysiological conditions in rodents, particularly after spinal cord injury (SCI). First, though the BBB restricts the permeation of large proteins, some cytokines and neurotrophic peptides/proteins in the periphery can reach the central nervous system (CNS) by specific transport systems...
September 20, 2016: CNS & Neurological Disorders Drug Targets
Laura Mahoney-Sanchez, Abdel Ali Belaidi, Ashley I Bush, Scott Ayton
Apolipoprotein E (ApoE) plays a crucial role in the homeostatic control of lipids in both the periphery and the central nervous system (CNS). In humans, ApoE exists in three different isoforms: ε2, ε3 and ε4. ApoE ε3 is the most common isoform, while the ε4 isoform confers the greatest genetic risk for Alzheimer's disease (AD). However, the mechanisms underlying how ApoE contributes to the pathogenesis of AD are still debated. ApoE has been shown to impact amyloid β (Aβ) deposition and clearance in the brain...
November 2016: Journal of Molecular Neuroscience: MN
Miles Herkenham, Stacey L Kigar
Clinical and basic studies of functional interactions between adaptive immunity, affective states, and brain function are reviewed, and the neural, humoral, and cellular routes of bidirectional communication between the brain and the adaptive immune system are evaluated.In clinical studies of depressed populations, lymphocytes-the principal cells of the adaptive immune system-exhibit altered T cell subtype ratios and CD4(+) helper T cell polarization profiles.In basic studies using psychological stress to model depression, T cell profiles are altered as well, consistent with stress effects conveyed by the hypothalamic-pituitary-adrenal axis and sympathetic nervous system...
September 6, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Natalia P Rocha, Fabiola M Ribeiro, Erin Furr-Stimming, Antonio L Teixeira
Huntington's disease (HD) is a neurodegenerative disorder characterized by selective loss of neurons in the striatum and cortex, which leads to progressive motor dysfunction, cognitive decline, and psychiatric disorders. Although the cause of HD is well described-HD is a genetic disorder caused by a trinucleotide (CAG) repeat expansion in the gene encoding for huntingtin (HTT) on chromosome 4p16.3-the ultimate cause of neuronal death is still uncertain. Apart from impairment in systems for handling abnormal proteins, other metabolic pathways and mechanisms might contribute to neurodegeneration and progression of HD...
2016: Mediators of Inflammation
Bora Lee, Seunghee Lee, Soo-Kyung Lee, Jae W Lee
Neurons in the hypothalamic arcuate nucleus relay and translate important cues from the periphery into the central nervous system. However, the gene regulatory program directing their development remains poorly understood. Here we report that the LIM-homeodomain transcription factor Isl1 is expressed in several subpopulations of developing arcuate neurons and plays crucial roles in their fate specification. Mice with conditional deletion of the Isl1 gene in developing hypothalamus display severe deficits in both feeding and linear growth...
August 30, 2016: Development
Xi Feng, Timothy D Jopson, Maria Serena Paladini, Sharon Liu, Brian L West, Nalin Gupta, Susanna Rosi
BACKGROUND: Primary central nervous system (CNS) neoplasms and brain metastases are routinely treated with whole-brain radiation. Long-term survival occurs in many patients, but their quality of life is severely affected by the development of cognitive deficits, and there is no treatment to prevent these adverse effects. Neuroinflammation, associated with activation of brain-resident microglia and infiltrating monocytes, plays a pivotal role in loss of neurological function and has been shown to be associated with acute and long-term effects of brain irradiation...
2016: Journal of Neuroinflammation
M G Pavlatou, A T Remaley, P W Gold
Klotho is a hormone secreted into human cerebrospinal fluid (CSF), plasma and urine that promotes longevity and influences the onset of several premature senescent phenotypes in mice and humans, including atherosclerosis, cardiovascular disease, stroke and osteoporosis. Preliminary studies also suggest that Klotho possesses tumor suppressor properties. Klotho's roles in these phenomena were first suggested by studies demonstrating that a defect in the Klotho gene in mice results in a significant decrease in lifespan...
August 30, 2016: Translational Psychiatry
Owein Guillemot-Legris, Julien Masquelier, Amandine Everard, Patrice D Cani, Mireille Alhouayek, Giulio G Muccioli
BACKGROUND: Obesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the central nervous system with regard to the inflammatory tone. METHODS: We used a diet-induced obesity model and compared at several time-points (1, 2, 4, 6, 8, and 16 weeks) a group of mice fed a high-fat diet with its respective control group fed a standard diet...
2016: Journal of Neuroinflammation
Fernanda Marques, João Carlos Sousa, Alexandra Brito, Jens Pahnke, Cecilia Santos, Margarida Correia-Neves, Joana Almeida Palha
This article brings the choroid plexus into the context of health and disease. It is remarkable that the choroid plexus, composed by the monolayer of epithelial cells that lie in a highly vascularized stroma, floating within the brain ventricles, gets so little attention in major physiology and medicine text books and in the scientific literature in general. Consider that it is responsible for producing most of the about 150mL of cerebrospinal fluid that fills the brain ventricles and the subarachnoid space and surrounds the spinal cord in the adult human brain, which is renewed approximately 2-3 times daily...
August 18, 2016: Neurobiology of Disease
Giuseppe P Cortese, Corinna Burger
Alzheimer's disease (AD) is a progressive neurodegenerative disease that targets memory and cognition, and is the most common form of dementia among the elderly. Although AD itself has been extensively studied, very little is known about early-stage preclinical events and/or mechanisms that may underlie AD pathogenesis. Since the majority of AD cases are sporadic in nature, advancing age remains the greatest known risk factor for AD. However, additional environmental and epigenetic factors are thought to accompany increasing age to play a significant role in the pathogenesis of AD...
August 17, 2016: Behavioural Brain Research
Sara Breid, Maria E Bernis, Julius T Babila, Maria C Garza, Holger Wille, Gültekin Tamgüney
UNLABELLED: α-Synuclein is a soluble, cellular protein that in a number of neurodegenerative diseases, including Parkinson's disease and multiple system atrophy, forms pathological deposits of protein aggregates. Because misfolded α-synuclein has some characteristics that resemble those of prions, we investigated its potential to induce disease after intraperitoneal or intraglossal challenge injection into bigenic Tg(M83(+/-):Gfap-luc(+/-)) mice, which express the A53T mutant of human α-synuclein and firefly luciferase...
October 15, 2016: Journal of Virology
Luc Bertrand, Madhavan Nair, Michal Toborek
Recent decades mark a great progress in the treatment of HIV infection. What was once a deadly disease is now a chronic infection. However, HIV-infected patients are prone to develop comorbidities, which severely affect their daily functions. For example, a large population of patients develop a variety of neurological and cognitive complications, called HIV associated neurological disorders (HAND). Despite efficient repression of viral replication in the periphery, evidence shows that the virus can remain active in the central nervous system (CNS)...
July 26, 2016: Current Pharmaceutical Design
Danbee Ha, So Jin Bing, Ginnae Ahn, Jinhee Kim, Jinhee Cho, Areum Kim, Kalahe H I N M Herath, Hak Sun Yu, Sangmee Ahn Jo, Ik-Hyun Cho, Youngheun Jee
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in the murine central nervous system (CNS) and recapitulates the clinical and pathological features of human multiple sclerosis (MS). Glutamate carboxipeptidase II (GCPII), an enzyme expressed exclusively on astrocytes, is known to affect the disease progression of various neurological disorders by producing glutamate. Despite several findings indicating possible link between glutamate and MS/EAE, however, the involvement of astrocyte or GCPII on glutamate excitotoxicity has not received much attention in MS/EAE...
September 2016: FEBS Journal
D E Harper, A Schrepf, D J Clauw
Until recently, most clinicians and scientists believed that the experience of pain is perceptually proportional to the amount of incoming peripheral nociceptive drive due to injury or inflammation in the area perceived to be painful. However, many cases of chronic pain have defied this logic, leaving clinicians perplexed as to how patients are experiencing pain with no obvious signs of injury in the periphery. Conversely, there are patients who have a peripheral injury and/or inflammation but little or no pain...
September 2016: Journal of Dental Research
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