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https://www.readbyqxmd.com/read/28821831/targeted-inhibition-of-rage-in-substantia-nigra-of-rats-blocks-6-ohda-induced-dopaminergic-denervation
#1
Juciano Gasparotto, Camila Tiefensee Ribeiro, Rafael Calixto Bortolin, Nauana Somensi, Thallita Kelly Rabelo, Alice Kunzler, Natália Cabral Souza, Matheus Augusto de Bittencourt Pasquali, José Claudio Fonseca Moreira, Daniel Pens Gelain
The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with inflammation in most cell types. RAGE up-regulates the expression of proinflammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson's disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA)...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821783/the-nadph-oxidase-nox2-mediates-loss-of-parvalbumin-interneurons-in-traumatic-brain-injury-human-autoptic-immunohistochemical-evidence
#2
Stefania Schiavone, Margherita Neri, Luigia Trabace, Emanuela Turillazzi
Pharmacological interventions for traumatic brain injury (TBI) are limited. Together with parvalbumin (PV) loss, increased production of reactive oxygen species (ROS) by the NADPH oxidase NOX enzymes represents a key step in TBI. Here, we investigated the contribution of NOX2-derived oxidative stress to the loss of PV immunoreactivity associated to TBI, performing immunohistochemistry for NOX2, 8-hydroxy-2'-deoxyguanosine (8OHdG) and PV on post mortem brain samples of subjects died following TBI, subjects died from spontaneous intracerebral hemorrhage (SICH) and controls (CTRL)...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821450/carvedilol-abrogates-hypoxia-induced-oxidative-stress-and-neuroinflammation-in-microglial-bv2-cells
#3
Xiujuan Gao, Bin Wu, Zhijian Fu, Zongwang Zhang, Guangjun Xu
Microglia initially undergo rapid activation in response to injury and stressful stimuli, such as hypoxia. Oxidative stress and the inflammatory response play critical roles in hypoxic-ischemic brain injury. Carvedilol is a β-blocker used to treat high blood pressure and heart failure. In this study, we investigated whether carvedilol had a protective effect against hypoxia-induced oxidative stress and inflammation in microglial BV2 cells. Our results indicate that hypoxic exposure significantly reduced mean cell viability of BV2 microglia, which was significantly restored by carvedilol (10 and 50μM)...
August 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28821008/trans-caryophyllene-inhibits-amyloid-%C3%AE-a%C3%AE-oligomer-induced-neuroinflammation-in-bv-2-microglial-cells
#4
Yawei Hu, Ziling Zeng, Baojie Wang, Shougang Guo
Amyloid β (Aβ) is the major component of senile plaques (SP) in the brains of Alzheimer's disease (AD) patients, and serves as an inflammatory stimulus for microglia. Trans-caryophyllene (TC), a major component in the essential oils derived from various species of medicinal plants, has displayed its neuro-protective effects in previous studies. However, whether TC has a protective role in AD remains unknown. In this study, the effects of TC on Aβ1-42-induced neuro-inflammation were investigated. We found that TC reduced the release of LDH in BV-2 microglial cells treated with Aβ1-42...
August 15, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28820181/microglia-activation-in-subjects-at-risk-for-psychosis-fact-or-fiction
#5
Patricio O'Donnell
Neuropsychopharmacology accepted article preview online, 18 August 2017. doi:10.1038/npp.2017.179.
August 18, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28820078/effects-of-excitotoxic-lesion-with-inhaled-anesthetics-on-nervous-system-cells-of-rodents
#6
Maria Fernanda Quiroz Padilla, Gemma Guillazo-Blanch, Magdy Sanchez, Maria Andrea Dominguez, Rosa Margaria Gomez
Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation...
August 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28819194/hdac3-inhibition-ameliorates-spinal-cord-injury-by-immunomodulation
#7
Tomoharu Kuboyama, Shalaka Wahane, Yong Huang, Xiang Zhou, Jamie K Wong, Andrew Koemeter-Cox, Michael Martini, Roland H Friedel, Hongyan Zou
Following spinal cord injury (SCI), the innate immune response of microglia and infiltrating macrophages clears up cellular debris and promotes tissue repair, but it also inflicts secondary injury from inflammatory responses. Immunomodulation aimed at maximizing the beneficial effects while minimizing the detrimental roles of the innate immunity may aid functional recovery after SCI. However, intracellular drivers of global reprogramming of the inflammatory gene networks in the innate immune cells are poorly understood...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817954/dissecting-amyloid-beta-deposition-using-distinct-strains-of-the-neurotropic-parasite-toxoplasma-gondii-as-a-novel-tool
#8
Carla M Cabral, Kathryn E McGovern, Wes R MacDonald, Jenna Franco, Anita A Koshy
Genetic and pathologic data suggest that amyloid beta (Aβ), produced by processing of the amyloid precursor protein, is a major initiator of Alzheimer's disease (AD). To gain new insights into Aβ modulation, we sought to harness the power of the coevolution between the neurotropic parasite Toxoplasma gondii and the mammalian brain. Two prior studies attributed Toxoplasma-associated protection against Aβ to increases in anti-inflammatory cytokines (TGF-β and IL-10) and infiltrating phagocytic monocytes. These studies only used one Toxoplasma strain making it difficult to determine if the noted changes were associated with Aβ protection or simply infection...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28817786/propofol-attenuates-bv2-microglia-inflammation-via-nmda-receptor-inhibition
#9
Qichao Wu, Yanjun Zhao, Xiangyuan Chen, Minmin Zhu, Changhong Miao
Activated microglia, involved in the occurrence and improvement of sepsis-associated encephalopathy, can induce the expression of pro-inflammatory cytokines and pro-inflammatory enzymes, resulting in inflammation-mediated neuronal cell death. It was reported that propofol could inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and pro-inflammatory enzymes expression in BV2 and primary microglial cells. However, the underlying mechanism is not well known. In the present study, we investigated whether and how propofol inhibited LPS-induced the expression of pro-inflammatory cytokines and pro-inflammatory enzymes in BV2 cells...
August 17, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28816544/animal-inflammation-based-models-of-depression-and-their-application-to-drug-discovery
#10
Li Ma, Konstantin A Demin, Tatyana O Kolesnikova, Sergey L Kharsko, Xiaokang Zhu, Xiaodong Yuan, Cai Song, Darya A Meshalkina, Brian E Leonard, Li Tian, Allan V Kalueff
Depression, anxiety and other affective disorders are globally widespread and severely debilitating human brain diseases. Despite their high prevalence and mental health impact, affective pathogenesis is poorly understood, and often remains recurrent and resistant to treatment. The lack of efficient antidepressants and presently limited conceptual innovation necessitate novel approaches and new drug targets in the field of antidepressant therapy. Areas covered: Herein, the authors discuss the emerging role of neuro-immune interactions in affective pathogenesis, which can become useful targets for CNS drug discovery, including modulating neuroinflammatory pathways to alleviate affective pathogenesis...
August 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28815942/plasma-membrane-protein-profiling-in-beta-amyloid-treated-microglia-cell-line
#11
Virginia Correani, Laura Di Francesco, Giuseppina Mignogna, Cinzia Fabrizi, Stefano Leone, Alessandra Giorgi, Alessia Passeri, Roberto Casata, Lorenzo Fumagalli, Bruno Maras, M Eugenia Schininà
In the responsiveness of microglia to toxic stimuli, plasma membrane proteins play a key role. In this study we treated with a synthetic beta amyloid peptide murine microglial cells metabolically differently labelled with stable isotope amino acids (SILAC). The plasma membrane was selectively enriched by a multi-stage aqueous two-phase partition system. We were able to identify by 1D-LC-MS/MS analyses 1577 proteins, most of them are plasma membrane proteins according to the Gene Ontology annotation. An unchanged level of amyloid receptors in this data set, suggests that microglia preserve their responsiveness capability to the environment even after 24 h-challenge with amyloid peptides...
August 16, 2017: Proteomics
https://www.readbyqxmd.com/read/28814744/monocyte-infiltration-and-proliferation-reestablish-myeloid-cell-homeostasis-in-the-mouse-retina-following-retinal-pigment-epithelial-cell-injury
#12
Wenxin Ma, Yikui Zhang, Chun Gao, Robert N Fariss, Johnny Tam, Wai T Wong
Age-related macular degeneration (AMD), a leading contributor of vision loss, currently lacks comprehensive treatment. While AMD histopathology involves retinal pigment epithelium (RPE) injury associated with immune cell infiltration, the nature of immune cell responses to RPE injury remains undefined. We induced RPE injury pharmacologically and genetically in transgenic mouse models in which microglia and systemic monocytes were separately tagged, enabling a spatial and temporal dissection of the relative contributions of microglia vs...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813718/transgenic-mice-over-expressing-rbp4-have-rbp4-dependent-and-light-independent-retinal-degeneration
#13
Mei Du, Eric Phelps, Michael J Balangue, Aaron Dockins, Gennadiy Moiseyev, Younghwa Shin, Shelley Kane, Laura Otalora, Jian-Xing Ma, Rafal Farjo, Krysten M Farjo
Purpose: Transgenic mice overexpressing serum retinol-binding protein (RBP4-Tg) develop progressive retinal degeneration, characterized by microglia activation, yet the precise mechanisms underlying retinal degeneration are unclear. Previous studies showed RBP4-Tg mice have normal ocular retinoid levels, suggesting that degeneration is independent of the retinoid visual cycle or light exposure. The present study addresses whether retinal degeneration is light-dependent and RBP4-dependent by testing the effects of dark-rearing and pharmacological lowering of serum RBP4 levels, respectively...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28813640/innate-immune-signaling-in-the-ventral-tegmental-area-contributes-to-drug-primed-reinstatement-of-cocaine-seeking
#14
Kyle T Brown, Sophia C Levis, Casey E O'Neill, Alexis L Northcutt, Timothy J Fabisiak, Linda R Watkins, Ryan K Bachtell
Cocaine addiction is a chronic relapsing disorder characterized by persistent perturbations to an organism's homeostatic processes that result in maladaptive drug seeking. Although considerable attention has been directed at the consequences of neuronal changes following chronic cocaine taking, few studies have examined the role of microglia, the brain's resident immune cells, following chronic cocaine administration. Toll-Like Receptor 4 (TLR4) is a molecular pattern receptor that recognizes pathogens, danger signals, and xenobiotics and induces proinflammatory signaling in the central nervous system...
August 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28812438/acute-formaldehyde-exposure-induced-early-alzheimer-like-changes-in-mouse-brain
#15
Xudong Liu, Yuchao Zhang, Ruliu Wu, Meng Ye, Yuqing Zhao, Jun Kang, Ping Ma, Jinquan Li, Xu Yang
Alzheimer's disease (AD) is a serious, common, global disease, yet its etiology and pathogenesis are incompletely understood. Although an association between AD and exposure to air pollutants has been discussed, the effects of pollutants on the functioning of the brain remain unclear. The indoor environment is where exposure to formaldehyde (FA) can occur. Whether exposure to FA contributes to the development of AD needs to be investigated. To determine the objective, C57BL/6 mice were exposed daily to FA (0, 0...
August 16, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28812311/nad-replenishment-with-nicotinamide-mononucleotide-protects-blood-brain-barrier-integrity-and-attenuates-delayed-tpa-induced-haemorrhagic-transformation-after-cerebral-ischemia
#16
Chun-Chun Wei, Yuan-Yuan Kong, Xia-Hua, Guo-Qiang Li, Si-Li Zheng, Ming-He Cheng, Pei Wang, Chao-Yu Miao
BACKGROUND AND PURPOSE: Tissue plasminogen activator (tPA) is the only approved pharmacological therapy for acute brain ischemia; however, a major limitation of tPA is the haemorrhagic transformation followed by tPA treatment. Here, we determine whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, would affect tPA-induced haemorrhagic transformation. EXPERIMENTAL APPROACH: Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 hours...
August 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28811143/nadph-oxidases-as-drug-targets-and-biomarkers-in-neurodegenerative-diseases-what-is-the-evidence
#17
REVIEW
Silvia Sorce, Roland Stocker, Tamara Seredenina, Rikard Holmdahl, Adriano Aguzzi, Adriano Chio, Antoine Depaulis, Freddy Heitz, Peter Olofsson, Tomas Olsson, Venceslas Duveau, Despina Sanoudou, Sara Skosgater, Antonia Vlahou, Dominique Wasquel, Karl-Heinz Krause, Vincent Jaquet
Neurodegenerative disease are frequently characterized by microglia activation and/or leukocyte infiltration in the parenchyma of the central nervous system and at the molecular level by increased oxidative modifications of proteins, lipids and nucleic acids. NADPH oxidases (NOX) emerged as a novel promising class of pharmacological targets for the treatment of neurodegeneration due to their role in oxidant generation and presumably in regulating microglia activation. The unique function of NOX is the generation of superoxide anion (O2(•-)) and hydrogen peroxide (H2O2)...
August 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28810892/absence-of-cx3cr1-impairs-the-internalization-of-tau-by-microglia
#18
Marta Bolós, María Llorens-Martín, Juan Ramón Perea, Jerónimo Jurado-Arjona, Alberto Rábano, Félix Hernández, Jesús Avila
BACKGROUND: Extracellular Tau is toxic for neighboring cells, and it contributes to the progression of AD. The CX3CL1/CX3CR1 axis is an important neuron/microglia communication mechanism. METHODS: We studied Tau clearance by microglia both in vitro (microglia primary cultures treated with Cy5-Tau, affinity chromatography to study the binding of Tau to CX3CR1, and Tau-CX3CL1 competition assays) and in vivo (stereotaxic injection of Cy5-Tau into WT and CX3CR1(-/-) mice)...
August 15, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28810545/electroacupuncture-attenuates-learning-and-memory-impairment-via-activation-of-%C3%AE-7nachr-mediated-anti-inflammatory-activity-in-focal-cerebral-ischemia-reperfusion-injured-rats
#19
Jiao Liu, Chunyan Li, Hongwei Peng, Kunqiang Yu, Jing Tao, Ruhui Lin, Lidian Chen
Studies have reported that electroacupuncture (EA) may reduce learning and memory impairment following cerebral ischemic injury. However, the precise mechanism of action remains unclear. In the present study, the attenuation of focal cerebral ischemia/reperfusion injury by EA in rats was investigated. EA at the Baihui (DU 20) and Shenting (DU 24) acupoints was demonstrated to significantly improve performance in the Morris water maze task, with shortened latency time and increased frequency of passing the platform...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810246/gper-agonist-g1-attenuates-neuroinflammation-and-dopaminergic-neurodegeneration-in-parkinson-disease
#20
Jing Guan, Beibei Yang, Yi Fan, Ji Zhang
OBJECTIVE: Epidemiological studies have shown that women of reproductive age have much less possibility of developing Parkinson disease (PD) than men. The beneficial effect of estrogen also has been well-described in both culture and animal models of PD. G protein-coupled estrogen receptor (GPER) is a membrane-associated estrogen receptor, and displayed a neuroprotective role in a mouse model of PD. Since GPER is highly expressed in microglia, we speculate that GPER mediates the neuroprotective function of estradiol through suppressing the neuroinflammation of PD...
August 16, 2017: Neuroimmunomodulation
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