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https://www.readbyqxmd.com/read/28521881/acute-fasting-inhibits-central-caspase-1-activity-reducing-anxiety-like-behavior-and-increasing-novel-object-and-object-location-recognition
#1
Albert E Towers, Maci L Oelschlager, Jay Patel, Stephen J Gainey, Robert H McCusker, Gregory G Freund
BACKGROUND: Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. METHODS: Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28503575/association-between-nlpr1-nlpr3-and-p2x7r-gene-polymorphisms-with-partial-seizures
#2
Haidong Wang, Pengfei Xu, Dehua Liao, Ruili Dang, Xin He, Yujin Guo, Pei Jiang
Objectives. Clinical and experimental evidence has clarified that the inflammatory processes within the brain play a pivotal role in the pathophysiology of seizures and epilepsy. Inflammasomes and P2X7 purinergic receptor (P2X7R) are important mediators during the inflammatory process. Therefore, we investigated the possible association between partial seizures and inflammasomes NLPR1, NLRP3, and P2X7R gene polymorphisms in the present study. Method. A total of 163 patients and 201 health controls were enrolled in this study and polymorphisms of NLPR1, NLRP3, and P2X7R genes were detected using polymerase chain reaction- (PCR-) ligase detection reaction method...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28477436/brain-inflammasomes-in-stroke-and-depressive-disorders-regulation-by-estrogen
#3
REVIEW
Alexander Slowik, Leoni Lammerding, Stefanie Hoffmann, Cordian Beyer
Neuroinflammation is a devastating pathophysiological process which ends up in brain damage and neuronal death. Pathogens, cell fragments and cellular dysfunction trigger inflammatory responses. Irrespective of the cause, inflammasomes are key intracellular multiprotein signaling platforms which sense neuropathological conditions. The activation of inflammasomes leads to the auto-proteolytic cleavage of caspase-1, resulting in the proteolysis of the pro-inflammatory cytokines interleukin (IL)1beta and IL18 into their bioactive forms...
May 6, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28475625/plasmodium-falciparum-histidine-rich-protein-ii-causes-vascular-leakage-and-exacerbates-experimental-cerebral-malaria-in-mice
#4
Priya Pal, Amanda E Balaban, Michael S Diamond, Photini Sinnis, Robyn S Klein, Daniel E Goldberg
A devastating complication of Plasmodium falciparum infection is cerebral malaria, in which vascular leakage and cerebral swelling lead to coma and often death. P. falciparum produces a protein called histidine-rich protein II (HRPII) that accumulates to high levels in the bloodstream of patients and serves as a diagnostic and prognostic marker for falciparum malaria. Using a human cerebral microvascular endothelial barrier model, we previously found that HRPII activates the endothelial cell inflammasome, resulting in decreased integrity of tight junctions and increased endothelial barrier permeability...
2017: PloS One
https://www.readbyqxmd.com/read/28470485/biomarkers-of-suicide-attempt-behavior-towards-a-biological-model-of-risk
#5
REVIEW
Katherin Sudol, J John Mann
PURPOSE OF REVIEW: The rising suicide rate in the USA will not be reversed without improved risk assessment and prevention practices. To date, the best method for clinicians to assess a patient's risk for suicide is screening for past suicide attempts in the patient and their family. However, neuroimaging, genomic, and biochemical studies have generated a body of findings that allow description of an initial heuristic biological model for suicidal behavior that may have predictive value...
June 2017: Current Psychiatry Reports
https://www.readbyqxmd.com/read/28455230/mangiferin-attenuates-blast-induced-traumatic-brain-injury-via-inhibiting-nlrp3-inflammasome
#6
Kaihua Fan, Jie Ma, Wenjing Xiao, Jingmin Chen, Juan Wu, Jiandong Ren, Jun Hou, Yonghe Hu, Jianwen Gu, Botao Yu
There is growing evidence that Mangiferin possess therapeutic benefit during neuroinflammation on various brain injury models due to its anti-inflammatory properties. It is reported that inflammatory plays a crucial role in the pathogenesis of secondary injury induced by the blast-induced traumatic brain injury (bTBI). However, the role of mangiferin in bTBI is yet to be studied. In our study, the potential effect of mangiferin in the duration of bTBI was examined first. Fortunately, the amelioration of cerebral cortex damage was found in rats suffering bTBI after mangiferin administration...
April 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28432035/expression-of-pattern-recognition-receptors-and-activation-of-the-non-canonical-inflammasome-pathway-in-brain-pericytes
#7
Ádám Nyúl-Tóth, Mihály Kozma, Péter Nagyőszi, Krisztina Nagy, Csilla Fazakas, János Haskó, Kinga Molnár, Attila E Farkas, Attila G Végh, György Váró, Péter Galajda, Imola Wilhelm, István A Krizbai
Cerebral pericytes are mural cells embedded in the basement membrane of capillaries. Increasing evidence suggests that they play important role in controlling neurovascular functions, i.e. cerebral blood flow, angiogenesis and permeability of the blood-brain barrier. These cells can also influence neuroinflammation which is highly regulated by the innate immune system. Therefore, we systematically tested the pattern recognition receptor expression of brain pericytes. We detected expression of NOD1, NOD2, NLRC5, NLRP1-3, NLRP5, NLRP9, NLRP10 and NLRX mRNA in non-treated cells...
April 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28427559/stress-induced-nlrp3-inflammasome-in-human-diseases
#8
Elísabet Alcocer-Gómez, Beatriz Castejón-Vega, Mario D Cordero
Stress is a complex event that induces disturbances to physiological and psychological homeostasis, and it may have a detrimental impact on certain brain and physiological functions. In the last years, a dual role of the stress effect has been studied in order to elucidate the molecular mechanism by which can induce physiological symptoms after psychological stress exposition and vice versa. In this sense, inflammation has been proposed as an important starring. And in the same line, the inflammasome complex has emerged to give responses because of its role of stress sensor...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28414101/autophagy-in-hemorrhagic-stroke-mechanisms-and-clinical-implications
#9
REVIEW
Haiying Li, Jiang Wu, Haitao Shen, Xiyang Yao, Chenglin Liu, S Pianta, J Han, C V Borlongan, Gang Chen
Accumulating evidence advances the critical role of autophagy in brain pathology after stroke. Investigations employing autophagy induction or inhibition using pharmacological tools or autophagy-related gene knockout mice have recently revealed the biological significance of intact and functional autophagy in stroke. Most of the reported cases attest to a pro-survival role for autophagy in stroke, by facilitating removal of damaged proteins and organelles, which can be recycled for energy generation and cellular defenses...
April 13, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28404595/nlr-members-nlrc4-and-nlrp3-mediate-sterile-inflammasome-activation-in-microglia-and-astrocytes
#10
Leslie Freeman, Haitao Guo, Clément N David, W June Brickey, Sushmita Jha, Jenny P-Y Ting
Inflammation in the brain accompanies several high-impact neurological diseases including multiple sclerosis (MS), stroke, and Alzheimer's disease. Neuroinflammation is sterile, as damage-associated molecular patterns rather than microbial pathogens elicit the response. The inflammasome, which leads to caspase-1 activation, is implicated in neuroinflammation. In this study, we reveal that lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and demyelination, elicits NLRP3 and NLRC4 inflammasome activation in microglia and astrocytes, which are central players in neuroinflammation...
May 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28401906/acrolein-acts-as-a-neurotoxin-in-the-nigrostriatal-dopaminergic-system-of-rat-involvement-of-%C3%AE-synuclein-aggregation-and-programmed-cell-death
#11
Yi-Ting Wang, Hui-Ching Lin, Wei-Zhong Zhao, Hui-Ju Huang, Yu-Li Lo, Hsiang-Tsui Wang, Anya Maan-Yuh Lin
Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson's disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150 nmoles/0.5 μl) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons in the infused SN as well as in striatal dopamine content...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28401330/cordycepin-confers-neuroprotection-in-mice-models-of-intracerebral-hemorrhage-via-suppressing-nlrp3-inflammasome-activation
#12
Yijun Cheng, Yongxu Wei, Wenlei Yang, Yaying Song, Hanbing Shang, Yu Cai, Zhebao Wu, Weiguo Zhao
Neuroinflammation has been recognized as a major contributor to brain injury caused by intracerebral hemorrhage (ICH). Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome acts as an important mediator of inflammatory response in various inflammation-related diseases including hemorrhagic insults. Cordycepin has recently been shown to possess anti-inflammatory effect; however, its role and the possible underlying mechanisms in ICH remain unclear. This study was designed to investigate the neuroprotective effect of cordycepin in mice models of ICH and to elucidate the underlying molecular mechanisms...
April 11, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28397070/ketone-bodies-as-anti-seizure-agents
#13
Timothy A Simeone, Kristina A Simeone, Jong M Rho
There is growing evidence that ketone bodies (KB)-derived from fatty acid oxidation and produced during fasting or consumption of high-fat diets-can exert broad neuroprotective effects. With respect to epilepsy, KB (such as β-hydroxybutyrate or BHB, acetoacetate and acetone) have been shown to block acutely induced and spontaneous recurrent seizures in various animal models. Although the mechanisms underlying the anti-seizure effects of KB have not been fully elucidated, recent experimental studies have invoked ketone-mediated effects on both inhibitory (e...
April 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28337127/nlrp3-inflammasome-in-neurological-diseases-from-functions-to-therapies
#14
REVIEW
Limin Song, Lei Pei, Shanglong Yao, Yan Wu, You Shang
Neuroinflammation has been identified as a causative factor of multiple neurological diseases. The nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome, a subcellular multiprotein complex that is abundantly expressed in the central nervous system (CNS), can sense and be activated by a wide range of exogenous and endogenous stimuli such as microbes, aggregated and misfolded proteins, and adenosine triphosphate, which results in activation of caspase-1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28331244/a-novel-role-for-brain-natriuretic-peptide-inhibition-of-il-1%C3%AE-secretion-via-downregulation-of-nf-kb-erk-1-2-and-nalp3-asc-caspase-1-activation-in-human-thp-1-monocyte
#15
Letizia Mezzasoma, Cinzia Antognelli, Vincenzo Nicola Talesa
Interleukin-1β (IL-1β) is a pleiotropic cytokine and a crucial mediator of inflammatory and immune responses. IL-1β processing and release are tightly controlled by complex pathways such as NF-kB/ERK1/2, to produce pro-IL-1β, and NALP3/ASC/Caspase-1 inflammasome, to produce the active secreted protein. Dysregulation of both IL-1β and its related pathways is involved in inflammatory/autoimmune disorders and in a wide range of other diseases. Identifying molecules modulating their expression is a crucial need to develop new therapeutic agents...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28326544/personalized-genetics-of-the-cholinergic-blockade-of-neuroinflammation
#16
REVIEW
Alon Simchovitz, Michael T Heneka, Hermona Soreq
Acetylcholine signaling is essential for cognitive functioning and blocks inflammation. To maintain homeostasis, cholinergic signaling is subjected to multi-leveled and bidirectional regulation by both proteins and non-coding microRNAs ('CholinomiRs'). CholinomiRs coordinate the cognitive and inflammatory aspects of cholinergic signaling by targeting major cholinergic transcripts including the acetylcholine hydrolyzing enzyme acetylcholinesterase (AChE). Notably, AChE inhibitors are the only currently approved line of treatment for Alzheimer's disease patients...
March 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#17
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28300164/role-of-purinergic-signaling-in-experimental-pneumococcal-meningitis
#18
Marco Zierhut, Susanne Dyckhoff, Ilias Masouris, Matthias Klein, Sven Hammerschmidt, Hans-Walter Pfister, Korcan Ayata, Marco Idzko, Uwe Koedel
Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1β pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7. Thus, we hypothesized involvement of ATP and P2Rs in PM. The functional role of ATP was investigated in a mouse meningitis model using P2R antagonists. Brain expression of P2Rs was assessed by RT-PCR...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28274860/purinergic-2x7-receptor-nlrp3-pathway-triggers-neuronal-apoptosis-after-ischemic-stroke-in-the-mouse
#19
Xinchun Ye, Tong Shen, Jinxia Hu, Liang Zhang, Yunshan Zhang, Lei Bao, Chengcheng Cui, Guoliang Jin, Kun Zan, Zuohui Zhang, Xinxin Yang, Hongjuan Shi, Jie Zu, Ming Yu, Chengjie Song, Yulan Wang, Suhua Qi, Guiyun Cui
Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950)...
March 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28270571/hiv-1-tat-primes-and-activates-microglial-nlrp3-inflammasome-mediated-neuroinflammation
#20
Ernest T Chivero, Ming-Lei Guo, Palsamy Periyasamy, Ke Liao, Shannon E Callen, Shilpa Buch
Neuroinflammation associated with HIV-1 infection is a problem affecting ∼50% of HIV-infected individuals. NLR family pyrin domain containing 3 (NLRP3) inflammasome has been implicated in HIV-induced microglial activation, but the mechanism(s) remain unclear. Because HIV-1 Transactivator of Transcription (Tat) protein continues to be present despite antiretroviral therapy and activates NF-kB, we hypothesized that Tat could prime the NLRP3 inflammasome. We found a dose- and time-dependent induction of NLRP3 expression in microglia exposed to Tat compared with control...
March 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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