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https://www.readbyqxmd.com/read/28807785/blocking-the-cd38-cadpr-pathway-plays-a-double-edged-role-in-lps-stimulated-microglia
#1
Yi-Min Wang, Zhi-Yong Liu, Yu-Hang Ai, Li-Na Zhang, Yu Zou, Qian-Yi Peng
Whether the CD38/cyclic ADP-ribose (cADPR) pathway plays a protective or detrimental role in neuroinflammation remains controversial. This study aimed to determine the role of CD38 in neuroinflammation using lipopolysaccharide (LPS)-stimulated BV2 microglial cells and co-cultured Neuro-2a (N2a) cells. In monoculture experiments, BV2 cells were divided into control, CD38 interference (CD38Ri), negative control (NC), LPS, CD38Ri+LPS, NC+LPS and 8-Br-cADPR+LPS groups. In co-culture experiments, N2a cells were co-cultured with BV2 cells for 48h...
August 12, 2017: Neuroscience
https://www.readbyqxmd.com/read/28800362/nucleotide-transmitters-atp-and-adp-mediate-intercellular-calcium-wave-communication-via-p2y12-13-receptors-among-bv-2-microglia
#2
Pengchong Jiang, Fulin Xing, Bu Guo, Jianyu Yang, Zheming Li, Wei Wei, Fen Hu, Imshik Lee, Xinzheng Zhang, Leiting Pan, Jingjun Xu
Nerve injury is accompanied by a liberation of diverse nucleotides, some of which act as 'find/eat-me' signals in mediating neuron-glial interplay. Intercellular Ca2+ wave (ICW) communication is the main approach by which glial cells interact and coordinate with each other to execute immune defense. However, the detailed mechanisms on how these nucleotides participate in ICW communication remain largely unclear. In the present work, we employed a mechanical stimulus to an individual BV-2 microglia to simulate localized injury...
2017: PloS One
https://www.readbyqxmd.com/read/28794655/p2y12-and-p2y13-receptors-involved-in-adp%C3%AE-s-induced-the-release-of-il-1%C3%AE-il-6-and-tnf-%C3%AE-from-cultured-dorsal-horn-microglia
#3
Pei-Wen Liu, Ming-Xia Yue, Rui Zhou, Juan Niu, Du-Juan Huang, Tao Xu, Pei Luo, Xiao-Hong Liu, Jun-Wei Zeng
OBJECTIVE: P2 receptors have been implicated in the release of neurotransmitter and pro-inflammatory cytokines due to their response to neuroexcitatory substances in the microglia. Dorsal horn P2Y12 and P2Y13 receptors are involved in the development of pain behavior induced by peripheral nerve injury. However, it is not known whether P2Y12 and P2Y13 receptors activation is associated with the expression and the release of interleukin-1B (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in cultured dorsal spinal cord microglia...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28698869/effects-of-poly-adp-ribose-polymerase-1-inhibition-in-a-neonatal-rodent-model-of-hypoxic-ischemic-injury
#4
Melanie Klöfers, Jules Kohaut, Ivo Bendix, Josephine Herz, Vinzenz Boos, Ursula Felderhoff-Müser, Mark Dzietko
BACKGROUND: Hypoxia ischemia (HI) to the developing brain occurs in 1-6 in 1000 live births. Large numbers of survivors have neurological long-term sequelae. However, mechanisms of recovery after HI are not understood and preventive measures or clinical treatments are not effective. Poly(ADP-ribose) polymerase-1 is overactivated in response to ischemia. In neonatal mice HI activates PARP-1 but its role in perinatal brain injury remains uncertain. OBJECTIVE: Aim of this study was to explore the effect of TES448 (PARP-1-inhibitor) and hypothermia after an ischemic insult...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28554197/a-new-neolignan-derivative-balanophonin-isolated-from-firmiana-simplex-delays-the-progress-of-neuronal-cell-death-by-inhibiting-microglial-activation
#5
Soo Young Lim, Lalita Subedi, Dongyun Shin, Chung Sub Kim, Kang Ro Lee, Sun Yeou Kim
Excessive activation of microglia causes the continuous production of neurotoxic mediators, which further causes neuron degeneration. Therefore, inhibition of microglial activation is a possible target for the treatment of neurodegenerative disorders. Balanophonin, a natural neolignoid from Firmiana simplex, has been reported to have anti-inflammatory and anti-cancer effects. In this study, we aimed to evaluate the anti-neuroinflammatory effects and mechanism of balanophonin in lipopolysaccharide (LPS)-stimulated BV2 microglia cells...
September 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28528700/directed-differentiation-of-human-pluripotent-stem-cells-to-microglia
#6
Panagiotis Douvaras, Bruce Sun, Minghui Wang, Ilya Kruglikov, Gregory Lallos, Matthew Zimmer, Cecile Terrenoire, Bin Zhang, Sam Gandy, Eric Schadt, Donald O Freytes, Scott Noggle, Valentina Fossati
Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs). Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28511952/lithium-ameliorates-lipopolysaccharide-induced-neurotoxicity-in-the-cortex-and-hippocampus-of-the-adult-rat-brain
#7
Muhammad Sohail Khan, Tahir Ali, Muhammad Noman Abid, Myeung Hoon Jo, Amjad Khan, Min Woo Kim, Gwang Ho Yoon, Eun Woo Cheon, Shafiq Ur Rehman, Myeong Ok Kim
Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor-kB (NF-KB) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α)...
May 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28461173/poly-adp-ribose-polymerase-1-regulates-microglia-mediated-decrease-of-endothelial-tight-junction-integrity
#8
Abbas Rezaeian Mehrabadi, Minna A Korolainen, Gary Odero, Donald W Miller, Tiina M Kauppinen
Alzheimer's disease pathology includes, beside neuronal damage, reactive gliosis and reduced blood-brain barrier (BBB) integrity. Microglia are intimately associated with the BBB and upon AD pathology, pro-inflammatory responses of microglia could contribute to BBB damage. To study whether microglia can directly affect BBB integrity, the effects of amyloid beta (Aβ) -stimulated primary murine microglia on co-cultured mouse brain endothelial cells (bEnd3) and murine astrocyte cultures were assessed. We also assessed whether microglial phenotype modulation via poly(ADP-ribose) polymerase-1 (PARP-1) inhibition/ablation can reverse microglial impact on these BBB forming cells...
April 28, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28376099/the-adenosine-generating-enzymes-cd39-cd73-control-microglial-processes-ramification-in-the-mouse-brain
#9
Marina Matyash, Oleksandr Zabiegalov, Stefan Wendt, Vitali Matyash, Helmut Kettenmann
Microglial cells invade the brain as amoeboid precursors and acquire a highly ramified morphology in the postnatal brain. Microglia express all essential purinergic elements such as receptors, nucleoside transporters and ecto-enzymes, including CD39 (NTPDase1) and CD73 (5'-nucleotidase), which sequentially degrade extracellular ATP to adenosine. Here, we show that constitutive deletion of CD39 and CD73 or both caused an inhibition of the microglia ramified phenotype in the brain with a reduction in the length of processes, branching frequency and number of intersections with Sholl spheres...
2017: PloS One
https://www.readbyqxmd.com/read/28322157/diabetes-related-neurological-implications-and-pharmacogenomics
#10
Rojas Carranza Camilo Andrés, Bustos Cruz Rosa Helena, Pino Pinzón Carmen Juliana, Ariza Marquez Yeimy Viviana, Gómez Bello Rosa Margarita, Cañadas Garre Marisa
Diabetes mellitus (DM) is the most commonly occurring cause of neuropathy around the world and is beginning to grow in countries where there is a risk of obesity. DM Type II, (T2DM) is a common age-related disease and is a major health concern, particularly in developed countries in Europe where the population is aging. T2DM is a chronic disease which is characterised by hyperglycemia, hyperinsulinemia and insulin resistance, together with the body's inability to use glucose as energy. Such metabolic disorder produces a chronic inflammatory state, as well as changes in lipid metabolism leading to hypertriglyceridemia, thereby producing chronic deterioration of the organs and premature morbidity and mortality...
March 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28144998/p2y12-receptors-in-primary-microglia-activate-nuclear-factor-of-activated-t-cell-signaling-to-induce-c-c-chemokine-3-expression
#11
Hidetoshi Tozaki-Saitoh, Hiroyuki Miyata, Tomohiro Yamashita, Katsuyuki Matsushita, Makoto Tsuda, Kazuhide Inoue
Microglia are widely accepted as surveillants in the central nervous system that are continually searching the local environment for signs of injury. Following an inflammatory situation, microglia alter their morphology, extend ramified processes, and undergo cell body hypertrophy. Extracellular nucleotides are recognized as a danger signal by microglia. ADP acting on P2Y12 receptors induce process extension of microglia thereby attracting microglia to the site of adenosine tri-phosphate/ADP leaking or release...
April 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28072413/decreased-hippocampal-translocator-protein-18%C3%A2-kda-expression-in-alcohol-dependence-a-11-c-pbr28-pet-study
#12
N J Kalk, Q Guo, D Owen, R Cherian, D Erritzoe, A Gilmour, A S Ribeiro, J McGonigle, A Waldman, P Matthews, J Cavanagh, I McInnes, K Dar, R Gunn, E A Rabiner, A R Lingford-Hughes
Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [(11)C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/27699246/mutyh-promotes-oxidative-microglial-activation-and-inherited-retinal-degeneration
#13
Shunji Nakatake, Yusuke Murakami, Yasuhiro Ikeda, Noriko Morioka, Takashi Tachibana, Kohta Fujiwara, Noriko Yoshida, Shoji Notomi, Toshio Hisatomi, Shigeo Yoshida, Tatsuro Ishibashi, Yusaku Nakabeppu, Koh-Hei Sonoda
Oxidative stress is implicated in various neurodegenerative disorders, including retinitis pigmentosa (RP), an inherited disease that causes blindness. The biological and cellular mechanisms by which oxidative stress mediates neuronal cell death are largely unknown. In a mouse model of RP (rd10 mice), we show that oxidative DNA damage activates microglia through MutY homolog-mediated (MUYTH-mediated) base excision repair (BER), thereby exacerbating retinal inflammation and degeneration. In the early stage of retinal degeneration, oxidative DNA damage accumulated in the microglia and caused single-strand breaks (SSBs) and poly(ADP-ribose) polymerase activation...
September 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/27663279/poly-adp-ribose-polymerase-is-not-involved-in-the-neuroprotection-exerted-by-azithromycin-against-ischemic-stroke-in-mice
#14
Francesco Petrelli, Mirko Muzzi, Alberto Chiarugi, Giacinto Bagetta, Diana Amantea
Repurposing azithromycin has recently emerged as a promising strategy for the acute treatment of ischemic stroke. The mechanism of neuroprotection depends on the ability of this macrolide to promote polarization of microglia/macrophages towards beneficial M2 phenotypes. The immunomodulatory and anti-inflammatory effects of azithromycin, well documented in chronic inflammatory airway diseases, have been ascribed to the inhibition of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1...
November 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27658543/platelet-cd40l-induces-activation-of-astrocytes-and-microglia-in-hypertension
#15
Shahnawaz Ali Bhat, Ruby Goel, Rakesh Shukla, Kashif Hanif
Studies have demonstrated separately that hypertension is associated with platelet activation in the periphery (resulting in accumulation and localized inflammatory response) and glial activation in the brain. We investigated the contribution of platelets in brain inflammation, particularly glial activation in vitro and in a rat model of hypertension. We found that HTN increased the expression of adhesion molecules like JAM-1, ICAM-1, and VCAM-1 on brain endothelium and resulted in the deposition of platelets in the brain...
January 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27444121/microglial-activation-induced-by-the-alarmin-s100b-is-regulated-by-poly-adp-ribose-polymerase-1
#16
Jianguo Xu, Handong Wang, Seok Joon Won, Jayinee Basu, David Kapfhamer, Raymond A Swanson
Brain injury resulting from stroke or trauma can be exacerbated by the release of proinflammatory cytokines, proteases, and reactive oxygen species by activated microglia. The microglial activation resulting from brain injury is mediated in part by alarmins, which are signaling molecules released from damaged cells. The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) has been shown to regulate microglial activation after brain injury, and here we show that signaling effects of the alarmin S100B are regulated by PARP-1...
November 2016: Glia
https://www.readbyqxmd.com/read/27339879/caspase-1-deficiency-alleviates-dopaminergic-neuronal-death-via-inhibiting-caspase-7-aif-pathway-in-mptp-p-mouse-model-of-parkinson-s-disease
#17
Chen Qiao, Lin-Xia Zhang, Xi-Yang Sun, Jian-Hua Ding, Ming Lu, Gang Hu
Caspase family has been recognized to be involved in dopaminergic (DA) neuronal death and to exert an unfavorable role in Parkinson's disease (PD) pathology. Our previous study has revealed that caspase-1, as an important component of NLRP3 inflammasome, induces microglia-mediated neuroinflammation in the pathogenesis of PD. However, the role of caspase-1 in DA neuronal degeneration in the onset of PD remains unclear. Here, we showed that caspase-1 knockout ameliorated DA neuronal loss and dyskinesia in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p)-induced PD model mice...
August 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/27215802/a-diphenyl-diselenide-supplemented-diet-and-swimming-exercise-promote-neuroprotection-reduced-cell-apoptosis-and-glial-cell-activation-in-the-hypothalamus-of-old-rats
#18
Marlon R Leite, José L Cechella, Simone Pinton, Cristina W Nogueira, Gilson Zeni
Aging is a process characterized by deterioration of the homeostasis of various physiological systems; although being a process under influence of multiple factors, the mechanisms involved in aging are not well understood. Here we investigated the effect of a (PhSe)2-supplemented diet (1ppm, 4weeks) and swimming exercise (1% of body weight, 20min per day, 4weeks) on proteins related to glial cells activation, apoptosis and neuroprotection in the hypothalamus of old male Wistar rats (27month-old). Old rats had activation of astrocytes and microglia which was demonstrated by the increase in the levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1) in hypothalamus...
September 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27157545/parp-inhibition-attenuates-early-brain-injury-through-nf-%C3%AE%C2%BAb-mmp-9-pathway-in-a-rat-model-of-subarachnoid-hemorrhage
#19
Ting Chen, Wei Wang, Jian-Ru Li, Hang-Zhe Xu, Yu-Cong Peng, Lin-Feng Fan, Feng Yan, Chi Gu, Lin Wang, Gao Chen
Poly (ADP-ribose) polymerases (PARPs) play an important role in a range of neurological disorders, however, the role of PARP in early brain injury after subarachnoid hemorrhage (SAH) remains unclear. This study was designed to explore the role and the potential mechanisms of PARP in early brain injury after SAH. Eighty-nine male SD rats were randomly divided into the Sham group, SAH+Vehicle group and SAH+PARP inhibitor (PJ34) group. An endovascular perforation model was used to induce SAH in rats. PJ34 (10mg/kg) or vehicle (0...
August 1, 2016: Brain Research
https://www.readbyqxmd.com/read/26637332/nf-%C3%AE%C2%BAb-transcriptional-activation-by-tnf%C3%AE-requires-phospholipase-c-extracellular-signal-regulated-kinase-2-and-poly-adp-ribose-polymerase-1
#20
Billy Vuong, Adam D J Hogan-Cann, Conrad C Alano, Mackenzie Stevenson, Wai Yee Chan, Christopher M Anderson, Raymond A Swanson, Tiina M Kauppinen
BACKGROUND: The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) is required for pro-inflammatory effects of TNFα. Our previous studies demonstrated that PARP-1 mediates TNFα-induced NF-κB activation in glia. Here, we evaluated the mechanisms by which TNFα activates PARP-1 and PARP-1 mediates NF-κB activation. METHODS: Primary cultures of mouse cortical astrocytes and microglia were treated with TNFα and suitable signaling pathway modulators (pharmacological and molecular)...
December 4, 2015: Journal of Neuroinflammation
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