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cns tnf signaling

Seok Roh Yoon, Cho Ara, Zhou Zixiong, Jeong Hyuneui, Park Jeong-Eun, Cha Youn-Soo, Oh Suk-Heung, Lim Chae-Woong, Kim Bumseok
<p>Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects...
October 17, 2016: Journal of Biomedical Research
Izhar Livne-Bar, Susy Lam, Darren Chan, Xiaoxin Guo, Idil Askar, Adrian Nahirnyj, John G Flanagan, Jeremy M Sivak
Reactive gliosis is an early pathological feature common to most neurodegenerative diseases, yet its regulation and impact remain poorly understood. Normally astrocytes maintain a critical homeostatic balance. After stress or injury they undergo rapid parainflammatory activation, characterized by hypertrophy, and increased polymerization of type III intermediate filaments (IFs), particularly glial fibrillary acidic protein and vimentin. However, the consequences of IF dynamics in the adult CNS remains unclear, and no pharmacologic tools have been available to target this mechanism in vivo...
2016: Cell Death & Disease
Denise Drago, Veronica Basso, Edoardo Gaude, Giulio Volpe, Luca Peruzzotti-Jametti, Angela Bachi, Giovanna Musco, Annapaola Andolfo, Christian Frezza, Anna Mondino, Stefano Pluchino
BACKGROUND: Neural stem cells (NSCs) display tissue trophic and immune modulatory therapeutic activities after transplantation in central nervous system disorders. The intercellular interplay between stem cells and target immune cells is increased in NSCs exposed to inflammatory cues. Here, we hypothesize that inflammatory cytokine signalling leads to metabolic reprogramming of NSCs regulating some of their immune modulatory effects. METHODS: NSC lines were prepared from the subventricular zone (SVZ) of 7-12-week-old mice...
2016: Journal of Neuroinflammation
Pau Gonzalez, Francisco Javier Rodríguez
Despite the essential functions of astrocytes and the emerging relevance of the Wnt family of proteins in the CNS under physiological and pathological conditions, the astroglial expression of this family of proteins and its potential modulatory role on astroglial activation is almost unknown. Thus, we have evaluated the expression of all Wnt ligands, receptors and regulators, and the activation state of Wnt-related signaling pathways in non-activated and differentially activated astroglial cultures. We found that numerous Wnt ligands, receptors and regulators were expressed in non-activated astrocytes, while the Wnt-dependent pathways were constitutively active...
August 22, 2016: Neuroscience Research
Martin Raasch, Knut Rennert, Tobias Jahn, Claudia Gärtner, Gilbert Schönfelder, Otmar Huber, Andrea E M Seiler, Alexander S Mosig
The development of therapeutic substances to treat diseases of the central nervous system is hampered by the tightness and selectivity of the blood-brain barrier. Moreover, testing of potential drugs is time-consuming and cost-intensive. Here, we established a new microfluidically supported, biochip-based model of the brain endothelial barrier in combination with brain cortical spheroids suitable to detect effects of neuroinflammation upon disruption of the endothelial layer in response to inflammatory signals...
July 2016: Biomicrofluidics
Michelle D Nemetchek, Andrea A Stierle, Donald B Stierle, Diana I Lurie
ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa monnieri (L) Wettst (common name, bacopa) is a medicinal plant used in Ayurveda, the traditional system of medicine of India, as a nootropic. It is considered to be a "medhya rasayana", an herb that sharpens the mind and the intellect. Bacopa is an important ingredient in many Ayurvedic herbal formulations designed to treat conditions such as memory loss, anxiety, poor cognition and loss of concentration. It has also been used in Ayurveda to treat inflammatory conditions such as arthritis...
July 26, 2016: Journal of Ethnopharmacology
Lori N Eidson, Kiyoshi Inoue, Larry J Young, Malu G Tansey, Anne Z Murphy
Opioid tolerance and the potential for addiction is a significant burden associated with pain management, yet its precise underlying mechanism and prevention remain elusive. Immune signaling contributes to the decreased efficacy of opioids, and we recently demonstrated that toll-like receptor 4 (TLR4)-mediated neuroinflammation in the periaqueductal gray (PAG) drives tolerance. Tumor necrosis factor (TNF), a product of TLR4 signaling, promotes inflammation and facilitates glutamatergic signaling, key components of opioid tolerance...
July 27, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Nitin B Gawali, Vipin D Bulani, Amrita A Chowdhury, Padmini S Deshpande, Dnyaneshwar M Nagmoti, Archana R Juvekar
Experimental and clinical evidence indicates that pro-inflammatory cytokines, oxidative stress and brain-derived neurotrophic factor (BDNF) signalling mechanisms play a role in the pathophysiology of depression. Agmatine is a neurotransmitter and/or neuromodulator that has emerged as a potential agent to manage diverse central nervous system disorders. Agmatine has been shown to exert antidepressant-like effect. The present study investigated ability of agmatine to abolish the depressive-like behaviour induced by the administration of the lipopolysaccharide (LPS) in mice...
October 2016: Pharmacology, Biochemistry, and Behavior
Priscila S Souza, Elaine D Gonçalves, Giulia S Pedroso, Hemelin R Farias, Stella C Junqueira, Rodrigo Marcon, Talita Tuon, Maíra Cola, Paulo C L Silveira, Adair R Santos, João B Calixto, Cláudio T Souza, Ricardo A de Pinho, Rafael C Dutra
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) caused by demyelination, immune cell infiltration, and axonal damage. Herein, we sought to investigate the influence of physical exercise on mice experimental autoimmune encephalomyelitis (EAE), a reported MS model. Data show that both strength and endurance training protocols consistently prevented clinical signs of EAE and decreased oxidative stress, an effect which was likely due to improving genomic antioxidant defense-nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response elements (ARE) pathway-in the CNS...
July 22, 2016: Molecular Neurobiology
Michael Willem
Neuregulin-1 (NRG1), known also as heregulin, acetylcholine receptor inducing activity (ARIA), glial growth factor (GGF), or sensory and motor neuron derived factor (SMDF), is a key factor for many developmental processes and in adult brain. All known splice variants contain an epidermal growth factor (EGF)-like domain, which is mediating signaling via receptors of the ErbB family. In particular, NRG1 acts as an essential signaling molecule expressed on the axonal surface, where it signals to Schwann cells throughout development and regulates the thickness of the myelin sheath...
July 5, 2016: Brain Research Bulletin
Yuichiro Takaoka, Moeka Takahashi, Yuki Kurauchi, Akinori Hisatsune, Takahiro Seki, Koichi Shudo, Hiroshi Katsuki
Accumulating lines of evidence suggest that retinoic acid receptor agonists such as Am80 exerts anti-inflammatory actions in the central nervous system, although detailed mechanisms of the action remain largely unknown. Our previous findings suggest that Am80 provides therapeutic effect on intracerebral hemorrhage in mice via suppression of expression of chemokine (C-X-C motif) ligand 2 (CXCL2). Here we investigated the mechanisms of inhibitory action of Am80 on expression of CXCL2 and other pro-inflammatory factors in microglial BV-2 cells...
September 2016: International Immunopharmacology
Rafael F O Franca, Renata S Costa, Jaqueline R Silva, Raphael S Peres, Leila R Mendonça, David F Colón, José Carlos Alves-Filho, Fernando Q Cunha
BACKGROUND: Viral encephalitis is a common cause of lethal infections in humans, and several different viruses are documented to be responsible. Rocio virus is a flavivirus that causes a severe lethal encephalitis syndrome in humans and also mice, providing an interesting model to study the CNS compartmentalized immune response. Interleukin 33 (IL-33), a member of the IL-1 family, is an immunomodulatory cytokine that is highly expressed in the CNS. However, the role of IL-33 on viral encephalitis remains unclear...
2016: Journal of Neuroinflammation
Felipe Schmitz, Paula Pierozan, André F Rodrigues, Helena Biasibetti, Matheus Grunevald, Letícia F Pettenuzzo, Giselli Scaini, Emilio L Streck, Carlos A Netto, Angela T S Wyse
Although the use, and misuse, of methylphenidate is increasing in childhood and adolescence, there is little information about the consequences of this psychostimulant chronic use on brain and behavior during development. The aim of the present study was to investigate hippocampus biochemical, histochemical, and behavioral effects of chronic methylphenidate treatment to juvenile rats. Wistar rats received intraperitoneal injections of methylphenidate (2.0 mg/kg) or an equivalent volume of 0.9 % saline solution (controls), once a day, from the 15th to the 45th day of age...
June 21, 2016: Molecular Neurobiology
Rodney M Ritzel, Sarah J Pan, Rajkumar Verma, John Wizeman, Joshua Crapser, Anita R Patel, Richard Lieberman, Royce Mohan, Louise D McCullough
PURPOSE: The transient middle cerebral artery occlusion (MCAO) model of stroke is one of the most commonly used models to study focal cerebral ischemia. This procedure also results in the simultaneous occlusion of the ophthalmic artery that supplies the retina. Retinal cell death is seen days after reperfusion and leads to functional deficits; however, the mechanism responsible for this injury has not been investigated. Given that the eye may have a unique ocular immune response to an ischemic challenge, this study examined the inflammatory response to retinal ischemia in the MCAO model...
2016: Molecular Vision
Xiang Zhang, Hongquan Dong, Nana Li, Susu Zhang, Jie Sun, Shu Zhang, Yanning Qian
BACKGROUND: Neuroinflammation plays a key role in the occurrence and development of postoperative cognitive dysfunction (POCD). Microglia, the resident immune cells in the brain, has been increasingly recognized to contribute to neuroinflammation. Although brain mast cells (MCs) are the "first responder" in the brain injury rather than microglia, little is known about the functional aspects of MCs-microglia interactions. METHODS: Male Sprague-Dawley (SD) rats were injected intracerebroventricular with MC stabilizer Cromolyn (100 μg/μl), MC stimulator C48/80 (1 μg/μl), or sterile saline 30 min before open tibial fracture surgery, and the levels of neuroinflammation and memory dysfunction were tested 1 and 3 days after surgery...
2016: Journal of Neuroinflammation
Aleksander R Zampronio, Denis M Soares, Glória E P Souza
Fever is a complex signal of inflammatory and infectious diseases. It is generally initiated when peripherally produced endogenous pyrogens reach areas that surround the hypothalamus. These peripheral endogenous pyrogens are cytokines that are produced by leukocytes and other cells, the most known of which are interleukin-1β, tumor necrosis factor-α, and interleukin-6. Because of the capacity of these molecules to induce their own synthesis and the synthesis of other cytokines, they can also be synthesized in the central nervous system...
October 2015: Temperature: Multidisciplinary Biomedical Journal
Song Yu, Xu Wang, Xingliang He, Yue Wang, Sujie Gao, Lu Ren, Yan Shi
Neuroinflammation is closely associated with the pathophysiology of neurodegenerative diseases including Parkinson's disease (PD). Recent evidence indicates that astrocytes also play pro-inflammatory roles in the central nervous system (CNS) by activation with toll-like receptor (TLR) ligands. Therefore, targeting anti-inflammation may provide a promising therapeutic strategy for PD. Curcumin, a polyphenolic compound isolated from Curcuma longa root, has been commonly used for the treatment of neurodegenerative diseases...
July 2016: Cell Stress & Chaperones
J-H Choi, J-B Lim, D D Wickramanayake, Y Wagley, J Kim, H-C Lee, H G Seo, T-H Kim, J-W Oh
MUDENG (Mu-2-related death-inducing gene, MuD) is revealed to be involved in cell death signaling. Astrocytes, the major glial cell type in the central nervous system, are a source of brain tumors. In this study, we examined MuD expression and function in human astroglioma cells. Stimulation of U251-MG cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resulted in a 40% decrease in cell viability and a 33% decrease in MuD protein levels, although not in MuD mRNA levels. To study the functional relevance of MuD expression, stable transfectants expressing high levels of MuD were generated...
2016: Oncogenesis
Tao Liu, Dong-xu Zhao, Hua Cui, Lei Chen, Ying-hui Bao, Yong Wang, Ji-yao Jiang
Necroptosis has been shown as an alternative form of cell death in many diseases, but the detailed mechanisms of the neuron loss after traumatic brain injury (TBI) in rodents remain unclear. To investigate whether necroptosis is induced after TBI and gets involved in the neuroprotecton of therapeutic hypothermia on the TBI, we observed the pathological and biochemical change of the necroptosis in the fluid percussion brain injury (FPI) model of the rats. We found that receptor-interacting protein (RIP) 1 and 3, and mixed lineage kinase domain-like protein (MLKL), the critical downstream mediators of necroptosis recently identified in vivo, as well as HMGB1 and the pro-inflammation cytokines TNF-α, IL-6 and IL-18, were increased at an early phase (6 h) in cortex after TBI...
2016: Scientific Reports
Hsin-Yi Huang, Hui-Fen Chang, Ming-Jen Tsai, Jhih-Si Chen, Mei-Jen Wang
BACKGROUND: The pathogenesis of several neurodegenerative diseases often involves the microglial activation and associated inflammatory processes. Activated microglia release pro-inflammatory factors that may be neurotoxic. 6-Mercaptopurine (6-MP) is a well-established immunosuppressive drug. Common understanding of their immunosuppressive properties is largely limited to peripheral immune cells. However, the effect of 6-MP in the central nervous system, especially in microglia in the context of neuroinflammation is, as yet, unclear...
2016: Journal of Neuroinflammation
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