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https://www.readbyqxmd.com/read/29916143/mast-cell-proteases-activate-astrocytes-and-glia-neurons-and-release-interleukin-33-by-activating-p38-and-erk1-2-mapks-and-nf-%C3%AE%C2%BAb
#1
Duraisamy Kempuraj, Ramasamy Thangavel, Gvindhasamy Pushpavathi Selvakumar, Mohammad Ejaz Ahmed, Smita Zaheer, Sudhanshu P Raikwar, Haris Zahoor, Daniyal Saeed, Iuliia Dubova, Gema Giler, Shelby Herr, Shankar S Iyer, Asgar Zaheer
Inflammatory mediators released from activated microglia, astrocytes, neurons, and mast cells mediate neuroinflammation. Parkinson's disease (PD) is characterized by inflammation-dependent dopaminergic neurodegeneration in substantia nigra. 1-Methyl-4-phenylpyridinium (MPP+ ), a metabolite of parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), induces inflammatory mediators' release from brain cells and mast cells. Brain cells' interaction with mast cells is implicated in neuroinflammation...
June 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29916142/lipotoxic-effects-of-palmitic-acid-on-astrocytes-are-associated-with-autophagy-impairment
#2
Ana Ortiz-Rodriguez, Estefania Acaz-Fonseca, Patricia Boya, Maria Angeles Arevalo, Luis M Garcia-Segura
Obesity is associated with an increase in the brain levels of saturated free fatty acids, such as palmitic acid (PA). Previous studies have shown that PA exerts proinflammatory actions and reduces cell viability in astrocyte cultures. In this study, we have assessed whether an alteration in autophagy is involved in the effects of PA on astrocytes. Primary astrocytes were obtained from the cerebral cortex of male and female CD1 mouse pups and were incubated for 4.5 or 24 h with 250-500 μM PA. PA increased the levels of LC3-II, an autophagosome marker, and reduced LC3-II flux in astrocytes, suggesting a blockade of autophagy...
June 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29915815/modeling-the-blood-brain-barrier-beyond-the-endothelial-cells
#3
Benjamin D Gastfriend, Sean P Palecek, Eric V Shusta
The blood-brain barrier (BBB) regulates the transport of ions, nutrients, and metabolites to help maintain proper brain function. This restrictive interface formed by brain microvascular endothelial cells excludes the majority of small and large molecule drugs from entering the brain, and blood-brain barrier dysfunction is a signature of many neurological diseases. Thus, in vitro models of the BBB based on brain endothelial cells have been developed to facilitate screening drugs for BBB permeability. However, while brain endothelial cells form the main interface, they work in concert with other brain-resident cells such as neural progenitor cells, pericytes, astrocytes, and neurons to form the neurovascular unit (NVU)...
March 2018: Current Opinion in Biomedical Engineering
https://www.readbyqxmd.com/read/29915582/imbalance-of-circulating-t-h-17-and-regulatory-t-cells-in-alzheimer-s-disease-a-case-control-study
#4
Timo Jan Oberstein, Lava Taha, Philipp Spitzer, Janina Hellstern, Martin Herrmann, Johannes Kornhuber, Juan Manuel Maler
The neuropathological hallmarks of Alzheimer's disease (AD), i.e., neuritic plaques and neurofibrillary tangles, consist of beta amyloid peptides (Aβ) and hyperphosphorylated Tau. These are accompanied by reactive microglia and astrocytes in the vicinity of the neuritic plaques and by changes to the peripheral immune system, e.g., an increase of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in the peripheral blood. To address a potential involvement of peripheral T helper cell (Th ) subsets in AD, we conducted a case control study with 54 individuals with AD dementia ( n  = 14), with mild cognitive impairment (MCI) due to AD (MCIAD , n  = 14), with MCI unlikely due to AD (MCIother , n  = 13), and controls without cognitive impairment (controls, n  = 13)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29915328/presymptomatic-change-in-micrornas-modulates-tau-pathology
#5
Salil Sharma, Ines Khadimallah, Adam Williamson Corya, Yousuf Omar Ali, Xi Rao, Yunlong Liu, Hui-Chen Lu
MicroRNAs (miRs) are 18~23 nucleotides long non-coding RNAs that regulate gene expression. To explore whether miR alterations in tauopathy contribute to pathological conditions, we first determined which hippocampal miRs are altered at the presymptomatic and symptomatic stages of tauopathy using rTg4510 mice (Tau mice), a well-characterized tauopathy model. miR-RNA pairing analysis using QIAGEN Ingenuity Pathway Analysis (IPA) revealed 401 genes that can be regulated by 71 miRs altered in Tau hippocampi at the presymptomatic stage...
June 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29915260/differential-antiviral-immunity-to-japanese-encephalitis-virus-in-developing-cortical-organoids
#6
Boya Zhang, Yangzhige He, Yanpeng Xu, Fan Mo, Tingwei Mi, Qing Sunny Shen, Chunfeng Li, Yali Li, Jing Liu, Yihui Wu, Guilai Chen, Wenliang Zhu, Chengfeng Qin, Baoyang Hu, Guomin Zhou
Japanese encephalitis (JE) caused by Japanese encephalitis virus (JEV) poses a serious threat to the world's public health yet without a cure. Certain JEV-infected neural cells express a subset of previously identified intrinsic antiviral interferon stimulated genes (ISGs), indicating brain cells retain autonomous antiviral immunity. However, whether this happens in composited brain remains unclear. Human pluripotent stem cell (hPSC)-derived organoids can model disorders caused by human endemic pathogens such as Zika virus, which may potentially address this question and facilitate the discovery of a cure for JE...
June 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29915258/a-recurrent-point-mutation-in-prkca-is-a-hallmark-of-chordoid-gliomas
#7
Shai Rosenberg, Iva Simeonova, Franck Bielle, Maite Verreault, Bertille Bance, Isabelle Le Roux, Mailys Daniau, Arun Nadaradjane, Vincent Gleize, Sophie Paris, Yannick Marie, Marine Giry, Marc Polivka, Dominique Figarella-Branger, Marie-Hélène Aubriot-Lorton, Chiara Villa, Alexandre Vasiljevic, Emmanuèle Lechapt-Zalcman, Michel Kalamarides, Ariane Sharif, Karima Mokhtari, Stefano Maria Pagnotta, Antonio Iavarone, Anna Lasorella, Emmanuelle Huillard, Marc Sanson
Chordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA D463H mutation. PRKCA encodes the Protein kinase C (PKC) isozyme alpha (PKCα) and is mutated in a wide range of human cancers. However the hot spot PRKCA D463H mutation was not described in other tumors. PRKCA D463H is strongly associated with the activation of protein translation initiation (EIF2) pathway...
June 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29915057/human-induced-pluripotent-stem-cell-derived-glial-cells-and-neural-progenitors-display-divergent-responses-to-zika-and-dengue-infections
#8
Julien Muffat, Yun Li, Attya Omer, Ann Durbin, Irene Bosch, Grisilda Bakiasi, Edward Richards, Aaron Meyer, Lee Gehrke, Rudolf Jaenisch
Maternal Zika virus (ZIKV) infection during pregnancy is recognized as the cause of an epidemic of microcephaly and other neurological anomalies in human fetuses. It remains unclear how ZIKV accesses the highly vulnerable population of neural progenitors of the fetal central nervous system (CNS), and which cell types of the CNS may be viral reservoirs. In contrast, the related dengue virus (DENV) does not elicit teratogenicity. To model viral interaction with cells of the fetal CNS in vitro, we investigated the tropism of ZIKV and DENV for different induced pluripotent stem cell-derived human cells, with a particular focus on microglia-like cells...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29914429/elevated-expression-of-hyaluronan-synthase-2-associates-with-decreased-survival-in-diffusely-infiltrating-astrocytomas
#9
Mari Valkonen, Hannu Haapasalo, Kirsi Rilla, Kristiina Tyynelä-Korhonen, Ylermi Soini, Sanna Pasonen-Seppänen
BACKGROUND: Diffusely infiltrating astrocytomas originate from astrocytic glial cells or their precursor cells and are the most common type of brain tumors in adults. In this retrospective study, we investigated the content of hyaluronan, its cell surface receptor, CD44 and the expression of hyaluronan metabolizing enzymes, in these aggressive tumors. Hyaluronan is the main component of extracellular matrix in the brain. In many tumors, aberrant hyaluronan metabolism implicates aggressive disease progression and metastatic potential...
June 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29913949/long-term-pain-neuroinflammation-and-glial-activation
#10
Elisabeth Hansson
Nociceptive and neuropathic pain signals are known to result from noxious stimuli, which are converted into electrical impulses within tissue nociceptors. There is a complex equilibrium of pain-signalling and pain-relieving pathways connecting PNS and CNS. Drugs against long-term pain are today directed against increased neuronal excitability, mostly with less success. An injury often starts with acute physiological pain, which becomes inflammatory, nociceptive, or neuropathic, and may be transferred into long-term pain...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913817/na-k-atpase-dependent-regulation-of-astrocyte-ca2-signalling-a-novel-mechanism-for-modulation-of-long-term-pain
#11
Elisabeth Hansson, Linda Block, Johan Forshammar, Christopher Lundborg, Björn Biber
Background Long-term or chronic pain represents a major health problem and is associated with significant socio-economic costs. During injury, pain can be dissociated from its normal physiological role. It can persist for a longer period of time, even after the primary noxious stimulus has more or less subsided. Analgesic drugs, with predominant neuronal sites of actions, seem to be relatively ineffective. Chronic pain is probably partly a consequence of ongoing neuroinflammation. The mechanisms behind these phenomena, and how the neuronal and non-neuronal activities evoked by painful stimuli and inflammation are processed in the brain and throughout the CNS, are not well understood...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913688/inflammation-reactive-astrocytes-can-be-restored-with-a-three-drug-combination
#12
E Hansson, L Block, U Björklund, B Biber
Aims In inflammation-reactive astrocytes the cell parameters, Ca2+ signalling, Na+ transporters, cytoskeleton, and release of proinflammatory cytokines are affected. We want to re-establish these parameters with agents, which might have a potential to restore the cells back to a normal non-inflammatory level. Methods Astrocytes in primary cultures were incubated with lipopolysaccharide (LPS) (10 ng/ml) for 24 h to become inflammation-reactive. Different parameters were analysed to verify this inflammation: Ca2+ signalling, Na+/K+-ATPase expression, actin filament organization, and interleukin-1beta release (IL-1β)...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913410/incensole-acetate-prevents-beta-amyloid-induced-neurotoxicity-in-human-olfactory-bulb-neural-stem-cells
#13
Mohammed A El-Magd, Sara F Khalifa, Faisal Abdulrahman A Alzahrani, Abdelnaser A Badawy, Eman S El-Shetry, Lamess M Dawood, Mohammed M Alruwaili, Hedib A Alrawaili, Engi F Risha, Fathy M El-Taweel, Hany E Marei
β-Amyloid peptide (Aβ) is a potent neurotoxic protein associated with Alzheimer's disease (AD) which causes oxidative damage to neurons. Incensole acetate (IA) is a major constituent of Boswellia carterii resin, which has anti-inflammatory and protective properties against damage of a large verity of neural subtypes. However, this neuroprotective effect was not studied on human olfactory bulb neural stem cells (hOBNSCs). Herein, we evaluated this effect and studied the underlying mechanisms. Exposure to Aβ25-35 (5 and 10 μM for 24 h) inhibited proliferation (revealed by downregulation of Nestin and Sox2 gene expression), and induced differentiation (marked by increased expression of the immature neuronal marker Map2 and the astrocyte marker Gfap) of hOBNSCs...
June 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29913244/during-development-ng2-glial-cells-of-the-spinal-cord-are-restricted-to-the-oligodendrocyte-lineage-but-generate-astrocytes-upon-acute-injury
#14
Wenhui Huang, Xianshu Bai, Laura Stopper, Bogdan Catalin, Luciana Politti Cartarozzi, Anja Scheller, Frank Kirchhoff
NG2 glia are self-renewal cells widely populating the entire central nervous system (CNS). The differentiation potential of NG2 glia in the brain has been systematically studied. However, the fate of NG2 glia in the spinal cord during development and after injury is still unclear. Here, we took advantage of faithful expression of Cre in NG2-CreERT2 knock-in mice to demonstrate that spinal NG2 glia remain committed to the oligodendrocyte (OL) lineage and generate OLs, but not astrocytes or neurons, during development...
June 15, 2018: Neuroscience
https://www.readbyqxmd.com/read/29913197/low-dose-cisplatin-causes-growth-inhibition-and-loss-of-autophagy-of-rat-astrocytes-in-vitro
#15
Nan Jiang, Chengjie Meng, Xiao Han, Guo Jun, Haoming Li, Zhengquan Yu
Astrocytes are the most abundant cell type in the central nervous system. Defects in astrocyte function have been implicated in a variety of diseases. Cisplatin (CDDP) is a chemotherapeutic drug that is widely used to treat various cancers. However, it causes neurocognitive impairment in patients. Little is known about the damaging effects of chemotherapeutic drugs like CDDP on astrocytes. Presently, we found that a low dose of CDDP distinctly inhibited astrocyte proliferation and induced delayed cell death...
June 15, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29913164/structural-and-visual-functional-deficits-in-a-rat-model-of-neuromyelitis-optica-spectrum-disorders-related-optic-neuritis
#16
Yuxin Zhang, Yiqin Bao, Wei Qiu, Lisheng Peng, Ling Fang, Ying Xu, Hui Yang
Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune astrocytopathies in the central nervous system, which are mainly caused by immunoglobulin G (IgG) against astrocyte water channel aquaporin-4 (AQP4). In this study, we aimed to establish a model of NMOSD-related optic neuritis (NMOSD-ON) and to evaluate the progressive changes of the optic nerve and visual function. AQP4 IgG-positive serum from NMOSD patients was injected into the subarachnoid space of the rat optic nerve to induce the NMOSD-ON model (AQP4 + group), and healthy serum was injected as the control...
June 15, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29911612/high-throughput-screening-reveals-enzyme-and-gpcr-targets-as-putative-binding-sites-for-d-deprenyl
#17
A Lesniak, A Jonsson, M Aarnio, T Norberg, F Nyberg, T Gordh
Aims In PET studies of patients suffering from chronic pain following whip lash trauma, d-deprenyl was shown to bind to painful sites in the neck [1]. High uptake points towards an existence of an inflammation-specific binding site. Thus, the aim of this study was to identify the binding site for d-deprenyl employing radioligand receptor binding and high-throughput analysis of its activity towards 165 G-protein coupled receptors and 84 enzyme targets commonly used in drug discovery and development. Methods D-Deprenyl activity towards GPCR targets was assessed by DiscoverX in CHO-K1 EDG1 β-arrest in EFC cell line utilizing the PathHunter™ technique...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29911589/perspectives-in-pain-research-2014-neuroinflammation-and-glial-cell-activation-the-cause-of-transition-from-acute-to-chronic-pain
#18
Brian E Cairns, Lars Arendt-Nielsen, Paola Sacerdote
Background It is unknown why an acute pain condition under various circumstances can transition into a chronic pain condition. There has been a shift towards neuroinflammation and hence glial cell activations specifically in the dorsal root ganglion and spinal cord as a mechanism possibly driving the transition to chronic pain. This has led to a focus on non-neuronal cells in the peripheral and central nervous system. Besides infiltrating macrophages, Schwann cells and satellite glial cells release cytokines and therefore important mechanisms in the maintenance of pain...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29910805/ip-10-promotes-blood-brain-barrier-damage-by-inducing-tumor-necrosis-factor-alpha-production-in-japanese-encephalitis
#19
Ke Wang, Haili Wang, Wenjuan Lou, Longhuan Ma, Yunchuan Li, Nan Zhang, Chong Wang, Fang Li, Muhammad Awais, Shengbo Cao, Ruiping She, Zhen F Fu, Min Cui
Japanese encephalitis is a neuropathological disorder caused by Japanese encephalitis virus (JEV), which is characterized by severe pathological neuroinflammation and damage to the blood-brain barrier (BBB). Inflammatory cytokines/chemokines can regulate the expression of tight junction (TJ) proteins and are believed to be a leading cause of BBB disruption, but the specific mechanisms remain unclear. IP-10 is the most abundant chemokine produced in the early stage of JEV infection, but its role in BBB disruption is unknown...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910000/biallelic-mutations-in-myorg-cause-autosomal-recessive-primary-familial-brain-calcification
#20
Xiang-Ping Yao, Xuewen Cheng, Chong Wang, Miao Zhao, Xin-Xin Guo, Hui-Zhen Su, Lu-Lu Lai, Xiao-Huan Zou, Xue-Jiao Chen, Yuying Zhao, En-Lin Dong, Ying-Qian Lu, Shuang Wu, Xiaojuan Li, Gaofeng Fan, Hongjie Yu, Jianfeng Xu, Ning Wang, Zhi-Qi Xiong, Wan-Jin Chen
Primary familial brain calcification (PFBC) is a genetically heterogeneous disorder characterized by bilateral calcifications in the basal ganglia and other brain regions. The genetic basis of this disorder remains unknown in a significant portion of familial cases. Here, we reported a recessive causal gene, MYORG, for PFBC. Compound heterozygous or homozygous mutations of MYORG co-segregated completely with PFBC in six families, with logarithm of odds (LOD) score of 4.91 at the zero recombination fraction...
June 6, 2018: Neuron
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