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https://www.readbyqxmd.com/read/28528700/directed-differentiation-of-human-pluripotent-stem-cells-to-microglia
#1
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...
May 18, 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
#2
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
#3
Abbas Rezaeian Mehrabadi, Minna A Korolainen, Gary Odero G, 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
#4
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
#5
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
#6
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...
January 31, 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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...
June 23, 2016: 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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/26519900/pharmacology-and-structure-of-p2y-receptors
#16
REVIEW
Ivar von Kügelgen, Kristina Hoffmann
P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. There are eight mammalian P2Y receptor subtypes (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14). P2Y receptors are widely expressed and play important roles in physiology and pathophysiology. One important example is the ADP-induced platelet aggregation mediated by P2Y1 and P2Y12 receptors. Active metabolites of the thienopyridine compounds ticlopidine, clopidogrel and prasugrel as well as the nucleoside analogue ticagrelor block P2Y12 receptors and thereby platelet aggregation...
May 2016: Neuropharmacology
https://www.readbyqxmd.com/read/26365310/lrrk2-g2019s-mutation-attenuates-microglial-motility-by-inhibiting-focal-adhesion-kinase
#17
Insup Choi, Beomsue Kim, Ji-Won Byun, Sung Hoon Baik, Yun Hyun Huh, Jong-Hyeon Kim, Inhee Mook-Jung, Woo Keun Song, Joo-Ho Shin, Hyemyung Seo, Young Ho Suh, Ilo Jou, Sang Myun Park, Ho Chul Kang, Eun-Hye Joe
In response to brain injury, microglia rapidly extend processes that isolate lesion sites and protect the brain from further injury. Here we report that microglia carrying a pathogenic mutation in the Parkinson's disease (PD)-associated gene, G2019S-LRRK2 (GS-Tg microglia), show retarded ADP-induced motility and delayed isolation of injury, compared with non-Tg microglia. Conversely, LRRK2 knockdown microglia are highly motile compared with control cells. In our functional assays, LRRK2 binds to focal adhesion kinase (FAK) and phosphorylates its Thr-X-Arg/Lys (TXR/K) motif(s), eventually attenuating FAK activity marked by decreased pY397 phosphorylation (pY397)...
September 14, 2015: Nature Communications
https://www.readbyqxmd.com/read/26200703/recurrent-hypoinsulinemic-hyperglycemia-in-neonatal-rats-increases-parp-1-and-nf-%C3%AE%C2%BAb-expression-and-leads-to-microglial-activation-in-the-cerebral-cortex
#18
Tate Gisslen, Kathleen Ennis, Vineet Bhandari, Raghavendra Rao
BACKGROUND: Hyperglycemia is a common metabolic problem in extremely low-birth-weight preterm infants. Neonatal hyperglycemia is associated with increased mortality and brain injury. Glucose-mediated oxidative injury may be responsible. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and cell survival. However, PARP-1 overactivation leads to cell death. NF-κB is coactivated with PARP-1 and regulates microglial activation. The effects of recurrent hyperglycemia on PARP-1/NF-κB expression and microglial activation are not well understood...
November 2015: Pediatric Research
https://www.readbyqxmd.com/read/25990044/role-of-toll-like-receptor-4-signaling-pathway-in-the-secondary-damage-induced-by-experimental-spinal-cord-injury
#19
Daniela Impellizzeri, Akbar Ahmad, Rosanna Di Paola, Michela Campolo, Michele Navarra, Emanuela Esposito, Salvatore Cuzzocrea
Toll-like receptors (TLRs) are signaling receptors in the innate immune system that is specific immunologic response to systemic bacterial infection and injury. TLRs contribute to the initial induction of neuroinflammation in the CNS. In spinal cord injury (SCI) intricate immune cell interactions are triggered, typically consisting of a staggered multiphasic immune cell response, which can become deregulated. The present study aims to evaluate the role of TLR4 signaling pathway in the development of secondary damage in a mouse model of SCI using TLR4-deficient (TLR4-KO) mice such as C57BL/10ScNJ and C3H/HeJ mice...
September 2015: Immunobiology
https://www.readbyqxmd.com/read/25847308/different-danger-signals-differently-impact-on-microglial-proliferation-through-alterations-of-atp-release-and-extracellular-metabolism
#20
Jimmy George, Francisco Q Gonçalves, Gonçalo Cristóvão, Lisa Rodrigues, José Roberto Meyer Fernandes, Teresa Gonçalves, Rodrigo A Cunha, Catarina A Gomes
Microglia rely on their ability to proliferate in the brain parenchyma to sustain brain innate immunity and participate in the reaction to brain damage. We now studied the influence of different danger signals activating microglia, both internal (typified by glutamate, associated with brain damage) and external (using a bacterial lipopolysaccharide, LPS), on the proliferation of microglia cells. We found that LPS (100 ng/mL) increased, whereas glutamate (0.5 mM) decreased proliferation. Notably, LPS decreased whereas glutamate increased the extracellular levels of ATP...
September 2015: Glia
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