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Locus Coeruleus AND immunity

Krishna L Bharani, Rebecca Derex, Ann-Charlotte Granholm, Aurélie Ledreux
Neuroinflammation is potentiated by early degeneration of the locus coeruleus noradrenergic pathway (LC-NE) commonly seen in aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In animal models, lipopolysaccharide (LPS) induces strong peripheral immune responses that can cause cognitive changes secondary to neuroinflammation. The influence of the peripheral immune response on cognition might be exacerbated by LC-NE degeneration, but this has not been well characterized previously...
2017: PloS One
Gabriel Shimizu Bassi, Daniel Penteado Martins Dias, Marcelo Franchin, Jhimmy Talbot, Daniel Gustavo Reis, Gustavo Batista Menezes, Jaci Airton Castania, Norberto Garcia-Cairasco, Leonardo Barbosa Moraes Resstel, Helio Cesar Salgado, Fernando Queiróz Cunha, Thiago Mattar Cunha, Luis Ulloa, Alexandre Kanashiro
Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera...
April 6, 2017: Brain, Behavior, and Immunity
Lin Kooi Ong, Erin A Fuller, Luba Sominsky, Deborah M Hodgson, Peter R Dunkley, Phillip W Dickson
Neonatal immune challenge with the bacterial mimetic lipopolysaccharide has the capacity to generate long-term changes in the brain. Neonatal rats were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg) on postnatal day (PND) 3 and again on PND 5. The activation state of tyrosine hydroxylase (TH) was measured in the locus coeruleus, ventral tegmental area and substantia nigra on PND 85. In the locus coeruleus there was an approximately four-fold increase in TH activity. This was accompanied by a significant increase in TH protein together with increased phosphorylation of all three serine residues in the N-terminal region of TH...
January 10, 2017: Scientific Reports
Hu Long, Yan Wang, Fan Jian, Li-Na Liao, Xin Yang, Wen-Li Lai
Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory and immune cells, and the release of neurogenic and pro-inflammatory mediators. Ultimately, endogenous analgesic mechanisms check the inflammatory response and the sensation of pain subsides. The orthodontic pain signal, once received by periodontal sensory endings, reaches the sensory cortex for pain perception through three-order neurons: the trigeminal neuron at the trigeminal ganglia, the trigeminal nucleus caudalis at the medulla oblongata and the ventroposterior nucleus at the thalamus...
June 30, 2016: International Journal of Oral Science
Hyun-ju Lee, Hyun-Jung Park, Angela Starkweather, Kyungeh An, Insop Shim
It has been demonstrated that immobilization (IMO) stress affects neuroimmune systems followed by alterations of physiology and behavior. Interleukin-4 (IL-4), an anti-inflammatory cytokine, is known to regulate inflammation caused by immune challenge but the effect of IMO on modulation of IL-4 expression in the brain has not been assessed yet. Here, it was demonstrated that IL-4 was produced by noradrenergic neurons in the locus coeruleus (LC) of the brain and release of IL-4 was reduced in response to IMO...
2016: Mediators of Inflammation
Chris Rudyk, Darcy Litteljohn, Shuaib Syed, Zach Dwyer, Shawn Hayley
A number of epidemiological and experimental studies have implicated the non-selective herbicide, paraquat, in the development of sporadic Parkinson's disease (PD). While preclinical research has focused mainly on elucidating the nigrostriatal effects of paraquat, relatively little data are available concerning non-motor brain systems and inflammatory immune processes (which have been implicated in PD). Hence, in the present study, we sought to take a multi-system approach to characterize the influence of paraquat upon extra-nigrostriatal brain regions, as well ascertain whether the impact of the pesticide might be enhanced in the context of chronic intermittent stressor exposure...
2015: Neurobiology of Stress
Boris Mravec, Katarina Lejavova, Peter Vargovic, Katarina Ondicova, Lubica Horvathova, Petr Novak, Georg Manz, Peter Filipcik, Michal Novak, Richard Kvetnansky
BACKGROUND: Brain norepinephrine (NE) plays an important role in the modulation of stress response and neuroinflammation. Recent studies indicate that in Alzheimer's disease (AD), the tau neuropathology begins in the locus coeruleus (LC) which is the main source of brain NE. Therefore, we investigated the changes in brain NE system and also the immune status under basal and stress conditions in transgenic rats over-expressing the human truncated tau protein. METHODS: Brainstem catecholaminergic cell groups (LC, A1, and A2) and forebrain subcortical (nucleus basalis of Meynert), hippocampal (cornu ammonis, dentate gyrus), and neocortical areas (frontal and temporal association cortices) were analyzed for NE and interleukin 6 (IL-6) mRNA levels in unstressed rats and also in rats exposed to single or repeated immobilization...
January 20, 2016: Journal of Neuroinflammation
Michael T Heneka, Monica J Carson, Joseph El Khoury, Gary E Landreth, Frederic Brosseron, Douglas L Feinstein, Andreas H Jacobs, Tony Wyss-Coray, Javier Vitorica, Richard M Ransohoff, Karl Herrup, Sally A Frautschy, Bente Finsen, Guy C Brown, Alexei Verkhratsky, Koji Yamanaka, Jari Koistinaho, Eicke Latz, Annett Halle, Gabor C Petzold, Terrence Town, Dave Morgan, Mari L Shinohara, V Hugh Perry, Clive Holmes, Nicolas G Bazan, David J Brooks, Stéphane Hunot, Bertrand Joseph, Nikolaus Deigendesch, Olga Garaschuk, Erik Boddeke, Charles A Dinarello, John C Breitner, Greg M Cole, Douglas T Golenbock, Markus P Kummer
Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction...
April 2015: Lancet Neurology
Michael D De Bellis, Abigail Zisk
Trauma in childhood is a psychosocial, medical, and public policy problem with serious consequences for its victims and for society. Chronic interpersonal violence in children is common worldwide. Developmental traumatology, the systemic investigation of the psychiatric and psychobiological effects of chronic overwhelming stress on the developing child, provides a framework and principles when empirically examining the neurobiological effects of pediatric trauma. This article focuses on peer-reviewed literature on the neurobiological sequelae of childhood trauma in children and in adults with histories of childhood trauma...
April 2014: Child and Adolescent Psychiatric Clinics of North America
Joaquim Cerejeira, Luísa Lagarto, Elizabeta B Mukaetova-Ladinska
Delirium is an acute neuropsychiatric syndrome characterized by acute-onset global cognitive deficits, perceptual and behavioural disturbances affecting mainly elderly subjects with underlying medical or surgical conditions. The pathophysiology of delirium is complex and inflammation is a relevant precipitant factor of this syndrome, although it remains unclear how acute systemic inflammation induces the clinical picture of delirium. The central nervous system is able to detect peripheral infection or tissue destruction through circulating immune mediators and neural ascending signs...
2014: Neuroimmunomodulation
Miriam Goebel-Stengel, Lixin Wang
Nesfatin-1 is the N-terminal fragment of nucleobindin-2 (NUCB2). The antibody against nesfatin-1 recognizes both full length of NUCB2 and nesfatin-1, thus the immunolabeling represents NUCB2/nesfatin-1. It has been found that NUCB2/nesfatin-1 is widely distributed in the rodent central nervous system. The immunoreactivity is more intensive in the brain autonomic centers that regulate feeding, neuroendocrine and cardiovascular functions, such as the hypothalamic paraventricular nucleus, supraoptic nucleus, lateral hypothalamic area, Edinger-Westphal nucleus, locus coeruleus, dorsal vagal complex and medullary raphe nuclei...
2013: Current Pharmaceutical Design
Teresa Botta-Orfila, Alex Sànchez-Pla, Manel Fernández, Francesc Carmona, Mario Ezquerra, Eduard Tolosa
LRRK2 mutations are the most common genetic cause of Parkinson's disease (PD). We performed a whole-genome RNA profiling of locus coeruleus post-mortem tissue, a histopathologically affected brain tissue in PD, from idiopathic PD (IPD) and LRRK2-associated PD patients. The differentially expressed genes found in IPD and LRRK2-associated PD are involved in the gene ontology terms of synaptic transmission and neuron projection. In addition, differentially expressed genes in the IPD group are associated with immune system related pathways...
July 23, 2012: Brain Research
Paul E Polak, Sergey Kalinin, David Braun, Anthony Sharp, Shao X Lin, Douglas L Feinstein
The endogenous neurotransmitter noradrenaline (NA) plays several roles in maintaining brain homeostasis, including exerting anti-inflammatory and neuroprotective effects. The primary source of NA in the CNS are tyrosine hydroxylase (TH)-positive neurons located in the Locus coeruleus (LC) which send projections throughout the brain and spinal cord. We recently demonstrated that dysregulation of the LC:Noradrenergic system occurs in experimental autoimmune encephalomyelitis as well as in MS patients, associated with damage occurring to LC neurons...
April 2012: Journal of Neurochemistry
Mak Adam Daulatzai
The pathophysiological mechanism(s) underlying Alzheimer's disease (AD) still remain unclear, and no disease-modifying or prophylactic therapies are currently available. Unraveling the fundamental neuropathogenesis of AD is an important challenge. Several studies on AD have suggested lesions in a number of CNS areas including the basal forebrain, hippocampus, entorhinal cortex, amygdale/insula, and the locus coeruleus. However, plausible unifying studies on the upstream factors that involve these heterogeneous regions and herald the onset of AD pathogenesis are not available...
April 2012: Neurochemical Research
Dona Lee Wong, T C Tai, David C Wong-Faull, Robert Claycomb, Edward G Meloni, Karyn M Myers, William A Carlezon, Richard Kvetnansky
Epinephrine (Epi), which initiates short-term responses to cope with stress, is, in part, stress-regulated via genetic control of its biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT). In rats, immobilization (IMMO) stress activates the PNMT gene in the adrenal medulla via Egr-1 and Sp1 induction. Yet, elevated Epi induced by acute and chronic stress is associated with stress induced, chronic illnesses of cardiovascular, immune, cancerous, and behavioral etiologies. Major sources of Epi include the adrenal medulla and brainstem...
July 2012: Cellular and Molecular Neurobiology
Paul E Polak, Sergey Kalinin, Douglas L Feinstein
The endogenous neurotransmitter noradrenaline exerts anti-inflammatory and neuroprotective effects in vitro and in vivo. Several studies report that noradrenaline levels are altered in the central nervous system of patients with multiple sclerosis and rodents with experimental autoimmune encephalomyelitis, which could contribute to pathology. Since the major source of noradrenaline are neurons in the locus coeruleus, we hypothesized that alterations in noradrenaline levels are a consequence of stress or damage to locus coeruleus neurons...
March 2011: Brain: a Journal of Neurology
Harald Engler, Raphael Doenlen, Carsten Riether, Andrea Engler, Hugo O Besedovsky, Adriana Del Rey, Gustavo Pacheco-López, Manfred Schedlowski
The neurotransmitter noradrenaline (NA) plays a pivotal role in immune regulation. Here we used the selective neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to investigate the impact of central NA depletion on cytokine production by splenic monocytes/macrophages and T cells. Intraperitoneal administration of DSP-4 in adult rats induced a substantial reduction of noradrenergic neurons in the locus coeruleus and the A5 cell group. The degeneration of brainstem noradrenergic neurons was accompanied by a significant decrease in the production of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha by lipopolysaccharide-stimulated splenocytes...
February 26, 2010: Journal of Neuroimmunology
Jung-Won Shin, Joel C Geerling, Arthur D Loewy
The ventrolateral bed nucleus of the stria terminalis (BSTvl) receives direct input from two specific subpopulations of neurons in the nucleus tractus solitarius (NTS). It is heavily innervated by aldosterone-sensitive NTS neurons, which are selectively activated by sodium depletion, and by the A2 noradrenergic neurons, which are activated by visceral and immune- and stress-related stimuli. Here, we used a retrograde neuronal tracer to identify other brain sites that innervate the BSTvl. Five general brain regions contained retrogradely labeled neurons: cerebral cortex (infralimbic and insular regions), rostral forebrain structures (subfornical organ, organum vasculosum of the lamina terminalis, taenia tecta, nucleus accumbens, lateral septum, endopiriform nucleus, dorsal BST, substantia innominata, and, most prominently the amygdala--primarily its basomedial and central subnuclei), thalamus (central medial, intermediodorsal, reuniens, and, most prominently the paraventricular thalamic nucleus), hypothalamus (medial preoptic area, perifornical, arcuate, dorsomedial, parasubthalamic, and posterior hypothalamic nuclei), and brainstem (periaqueductal gray matter, dorsal and central superior raphe nuclei, parabrachial nucleus, pre-locus coeruleus region, NTS, and A1 noradrenergic neurons in the caudal ventrolateral medulla)...
December 10, 2008: Journal of Comparative Neurology
Seo-Yeon Yoon, Young-Bae Kwon, Hyun-Woo Kim, Dae-Hyun Roh, Hyoung-Sig Seo, Ho-Jae Han, Hye-Jung Lee, Alvin J Beitz, Sun-Wook Hwang, Jang-Hern Lee
There are several reports indicating that the locus coeruleus (LC) is capable of altering immune responses. Moreover, it is well established that the LC is the major source of descending noradrenergic system. Recently we have demonstrated that subcutaneous bee venom (BV) injection dramatically suppressed peripheral inflammation through activation of sympathetic preganglionic neurons (SPNs) leading to release of adreno-medullary catecholamines. Importantly, this 'BV-induced anti-inflammatory effect' (BVAI) is also associated with an increase of the activity of LC...
September 2007: Neuroscience Research
C Tsatsanis, E Dermitzaki, M Venihaki, E Chatzaki, V Minas, A Gravanis, A N Margioris
Corticotropin-releasing factor (CRF), also termed corticotropin-releasing hormone (CRH) or corticoliberin, is the major regulator of the adaptive response to internal or external stresses. An essential component of the adaptation mechanism is the adrenal gland. CRF regulates adrenal function indirectly through the central nervous system (CNS) via the hypothalamic-pituitary-adrenal (HPA) axis and via the autonomic nervous system by way of locus coeruleus (LC) in the brain stem. Accumulating evidence suggests that CRF and its related peptides also affect the adrenals directly, i...
July 2007: Cellular and Molecular Life Sciences: CMLS
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