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https://www.readbyqxmd.com/read/27911303/amylin-treatment-reduces-neuroinflammation-and-ameliorates-abnormal-patterns-of-gene-expression-in%C3%A2-the-cerebral-cortex-of-an-alzheimer-s-disease-mouse-model
#1
Erming Wang, Haihao Zhu, Xiaofan Wang, Adam Gower, Max Wallack, Jan Krzysztof Blusztajn, Neil Kowall, Wei Qiao Qiu
Our recent study has demonstrated that peripheral amylin treatment reduces the amyloid pathology in the brain of Alzheimer's disease (AD) mouse models, and improves their learning and memory. We hypothesized that the beneficial effects of amylin for AD was beyond reducing the amyloids in the brain, and have now directly tested the actions of amylin on other aspects of AD pathogenesis, especially neuroinflammation. A 10-week course of peripheral amylin treatment significantly reduced levels of cerebral inflammation markers, Cd68 and Iba1, in amyloid precursor protein (APP) transgenic mice...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27903721/cross-talk-between-brain-innate-immunity-and-serotonin-signaling-underlies-depressive-like-behavior-induced-by-alzheimer-s-amyloid-%C3%AE-oligomers-in-mice
#2
Jose Henrique Ledo, Estefania P Azevedo, Danielle Beckman, Felipe C Ribeiro, Luis E Santos, Daniela S Razolli, Grasielle C Kincheski, Helen M Melo, Maria Bellio, Antonio L Teixeira, Licio A Velloso, Debora Foguel, Fernanda G De Felice, Sergio T Ferreira
: Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) and depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble Aβ oligomers (AβOs), toxins that accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depressive-like behavior in mice. Here, we report that the mechanism underlying this action involves AβO-induced microglial activation, aberrant TNF-α signaling, and decreased brain serotonin levels...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27896432/repression-of-telomere-associated-genes-by-microglia-activation-in-neuropsychiatric-disease
#3
Golo Kronenberg, Ria Uhlemann, Johanna Schöner, Stephanie Wegner, Valérie Boujon, Nikolas Deigendesch, Matthias Endres, Karen Gertz
Microglia senescence may promote neuropsychiatric disease. This prompted us to examine the relationship between microglia activation states and telomere biology. A panel of candidate genes associated with telomere maintenance, mitochondrial biogenesis, and cell-cycle regulation were investigated in M1- and M2-polarized microglia in vitro as well as in MACS-purified CD11b+ microglia/brain macrophages from models of stroke, Alzheimer's disease, and chronic stress. M1 polarization, ischemia, and Alzheimer pathology elicited a strikingly similar transcriptomic profile with, in particular, reduced expression of murine Tert...
November 28, 2016: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/27878757/targeting-ccr3-to-reduce-amyloid-%C3%AE-production-tau-hyperphosphorylation-and-synaptic-loss-in-a-mouse-model-of-alzheimer-s-disease
#4
Chunyan Zhu, Bing Xu, Xiaohong Sun, Qiwen Zhu, Yi Sui
The majority of Alzheimer's disease (AD) patients have a late onset, and chronic neuroinflammation, characterized by glial activation and secretion of pro-inflammatory cytokines and chemokines, plays a role in the pathogenesis of AD. The chemokine CCL11 has been shown to be a causative factor of cognitive decline in the process of aging, but little is known whether it is involved in the pathogenesis of AD. In the present study, we showed that CCR3, the receptor for CCL11, was expressed by hippocampal neurons and treatment of primary hippocampal neuronal cultures (14 days in vitro) with CCL11 resulted in activation of cyclin-dependent kinase 5 and glycogen synthase kinase-3β, associated with elevated tau phosphorylation at multiple sites...
November 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27875002/superparamagnetic-nanoparticle-enhanced-mri-of-alzheimer-s-disease-plaques-and-activated-microglia-in-3x-transgenic-mouse-brains-contrast-optimization
#5
Marissa A Tafoya, Saaussan Madi, Laurel O Sillerud
PURPOSE: To optimize magnetic resonance imaging (MRI) of antibody-conjugated superparamagnetic nanoparticles for detecting amyloid-β plaques and activated microglia in a 3X transgenic mouse model of Alzheimer's disease. MATERIALS AND METHODS: Ten 3X Tg mice were fed either chow or chow containing 100 ppm resveratrol. Four brains, selected from animals injected with either anti-amyloid targeted superparamagnetic iron oxide nanoparticles, or anti-Iba-1-conjugated FePt-nanoparticles, were excised, fixed with formalin, and placed in Fomblin for ex vivo MRI (11...
November 22, 2016: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/27871289/inhibition-of-stat3-and-mapk-dependent-pge2-synthesis-ameliorates-phagocytosis-of-fibrillar-%C3%AE-amyloid-peptide-1-42-via-ep2-receptor-in-emf-stimulated-n9-microglial-cells
#6
Gen-Lin He, Zhen Luo, Ting-Ting Shen, Ping Li, Ju Yang, Xue Luo, Chun-Hai Chen, Peng Gao, Xue-Sen Yang
BACKGROUND: Prostaglandin E2 (PGE2)-involved neuroinflammatory processes are prevalent in several neurological conditions and diseases. Amyloid burden is correlated with the activation of E-prostanoid (EP) 2 receptors by PGE2 in Alzheimer's disease. We previously demonstrated that electromagnetic field (EMF) exposure can induce pro-inflammatory responses and the depression of phagocytosis in microglial cells, but the signaling pathways involved in phagocytosis of fibrillar β-amyloid (fAβ) in microglial cells exposed to EMF are poorly understood...
November 21, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27863488/mathematical-model-on-alzheimer-s-disease
#7
Wenrui Hao, Avner Friedman
BACKGROUND: Alzheimer disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive skills. AD is characterized by the presence of two types of neuropathological hallmarks: extracellular plaques consisting of amyloid β-peptides and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins. The disease affects 5 million people in the United States and 44 million world-wide. Currently there is no drug that can cure, stop or even slow the progression of the disease...
November 18, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/27862631/microglia-show-altered-morphology-and-reduced-arborisation-in-human-brain-during-aging-and-alzheimer-s-disease
#8
Danielle S Davies, Jolande Ma, Thuvarahan Jegathees, And Claire Goldsbury
Changes in microglia function are involved in Alzheimer's disease (AD) for which ageing is the major risk factor. We evaluated microglial cell process morphologies and their grey matter coverage (arborized area) during ageing and in the presence and absence of AD pathology in autopsied human neocortex. Microglial cell processes were reduced in length, showed less branching and reduced arborized area with aging (case range 52-98 yrs). This occurred during normal ageing and without microglia dystrophy or changes in cell density...
November 14, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27862351/p2y12-receptor-is-expressed-on-human-microglia-under-physiological-conditions-throughout-development-and-is-sensitive-to-neuroinflammatory-diseases
#9
Alexander Mildner, Hao Huang, Josefine Radke, Werner Stenzel, Josef Priller
Microglia are resident immune cells in the central nervous system (CNS), which are essential for immune defence and critically contribute to neuronal functions during homeostasis. Until now, little is known about microglia biology in humans in part due to the lack of microglia-specific markers. We therefore investigated the expression of the purinergic receptor P2Y12 in human brain tissue. Compared to classical markers used to identify microglia such as Iba1, CD68 or MHCII, we found that P2Y12 is expressed on parenchymal microglia but is absent from perivascular or meningeal macrophages...
November 12, 2016: Glia
https://www.readbyqxmd.com/read/27859676/microglia-and-brain-macrophages-an-update
#10
REVIEW
Atsushi Sasaki
Current immunohistochemical techniques have made the identification of microglia possible in routinely processed tissue sections from human brains. Previous studies have indicated that almost no neurological diseases exist without microglial activation. Activated microglia often secrete inflammatory cytokines in various diseases, including Alzheimer's disease, but microglial activation is not always associated with inflammation. The equation microglial activation means "neuroinflammation" is absurd and misleading...
November 18, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/27855618/scutellarin-as-a-therapeutic-agent-in-microglia-mediated-neuroinflammation-in-cerebral-ischemia
#11
Chun-Yun Wu, Ming Fang, Aparna Karthikeyan, Yun Yuan, Eng-Ang Ling
Neuroinflammation plays an important role in different brain diseases including acute brain injuries such as cerebral ischemic stroke and chronic neurodegenerative diseases e.g. Alzheimer's disease etc. The central player in this is the activated microglia which produce substantial amounts of proinflammatory mediators that may exacerbate the disease. Associated with microglia activation is astrogliosis characterized by hypertrophic astrocytes with increased expression of proinflammatory cytokines, neurotrophic factors, stem cell, neuronal and proliferation markers, all these are crucial for reconstruction of damaged tissue and ultimate restoration of neurological functions...
November 18, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27846826/natural-product-htp-screening-for-antibacterial-e-coli-0157-h7-and-anti-inflammatory-agents-in-lps-from-e-coli-o111-b4-activated-macrophages-and-microglial-cells-focus-on-sepsis
#12
Elizabeth A Mazzio, Nan Li, David Bauer, Patricia Mendonca, Equar Taka, Mohammed Darb, Leeshawn Thomas, Henry Williams, Karam F A Soliman
BACKGROUND: Acute systemic inflammatory response syndrome arising from infection can lead to multiple organ failure and death, with greater susceptibility occurring in immunocompromised individuals. Moreover, sub-acute chronic inflammation is a contributor to the pathology of diverse degenerative diseases (Parkinson's disease, Alzheimer's disease and arthritis). Given the known limitations in Western medicine to treat a broad range of inflammatory related illness as well as the emergence of antibiotic resistance, there is a renewed interest in complementary and alternative medicines (CAMs) to achieve these means...
November 15, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27844286/mfg-e8-selectively-inhibited-a%C3%AE-induced-microglial-m1-polarization-via-nf-%C3%AE%C2%BAb-and-pi3k-akt-pathways
#13
Xiaolei Shi, Xiaoying Cai, Wei Di, Jie Li, Xiaotian Xu, Aiwu Zhang, Weiwei Qi, Zhiming Zhou, Yannan Fang
Activated microglia are classified into two specific states: classically activated (M1) and alternatively activated (M2) subtypes. It is believed that the polarization of M1/M2 phenotype plays an important role in Alzheimer's disease (AD). However, the mechanisms regulating this process remain unclear. Thus, we addressed this question focusing on milk fat globule epidermal growth factor 8 (MFG-E8). MFG-E8 is a unique protein which can bind to microglia and regulate its inflammatory responses. It is speculated that it might play a role in the balance of microglial polarization...
November 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27837191/age-associated-physiological-and-pathological-changes-at-the-blood-brain-barrier-a-review
#14
REVIEW
Franciska Erdő, László Denes, Elizabeth de Lange
The age-associated decline of the neurological and cognitive functions becomes more and more serious challenge for the developed countries with the increasing number of aged populations. The morphological and biochemical changes in the aging brain are the subjects of many extended research projects worldwide for a long time. However, the crucial role of the blood-brain barrier (BBB) impairment and disruption in the pathological processes in age-associated neurodegenerative disorders received special attention just for a few years...
November 11, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27830533/analysis-of-the-impact-of-cd200-on-phagocytosis
#15
Anthony Lyons, Aedín M Minogue, Raasay S Jones, Orla Fitzpatrick, Janis Noonan, Veronica A Campbell, Marina A Lynch
One factor that impacts on microglial activation is the interaction between the ubiquitously expressed CD200 and CD200R, which is expressed only on microglia in the brain. Decreased signalling through CD200R, when CD200 expression is reduced, results in microglial activation and may, at least in part, explain the increased cell activity that is observed with age, in models of Alzheimer's and Parkinson's disease as well as in the human diseases. There is evidence of increased microglial activation in CD200-deficient mice, and isolated microglia prepared from these mice are more reactive to inflammatory stimuli like Toll-like receptor 2 and 4 agonists, and interferon-γ...
November 9, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27825966/hypericin-inhibits-oligomeric-amyloid-%C3%AE-42-induced-inflammation-response-in-microglia-and-ameliorates-cognitive-deficits-in-an-amyloid-%C3%AE-injection-mouse-model-of-alzheimer-s-disease-by-suppressing-mkl1
#16
Mu Zhang, Yanyan Wang, Fei Qian, Ping Li, Xiaojun Xu
Amyloid β (Aβ) provokes severe inflammation response in the central nervous system, which is a key risk factor for the progression of Alzheimer's disease (AD). Anti-inflammation medications shed light on treating AD. In this study, we found hypericin is a potent anti-AD constituent through anti-inflammation. Pretreatment with hypericin (5 μM and 15 μM) significantly suppresses oligomeric Aβ42 (oAβ42)-induced expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF α) and inducible nitric oxide synthase (iNOS) and production of NO in microglia without cytotoxicity...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27823627/anti-neuroinflammatory-effect-of-sophoraflavanone-g-from-sophora-alopecuroides-in-lps-activated-bv2-microglia-by-mapk-jak-stat-and-nrf2-ho-1-signaling-pathways
#17
Chao Guo, Lei Yang, Chuan-Xing Wan, Yuan-Zheng Xia, Chao Zhang, Meng-Han Chen, Zhen-Dong Wang, Zhong-Rui Li, Xue-Mei Li, Ya-Di Geng, Ling-Yi Kong
BACKGROUND: Neuroinflammation plays a vital role in Alzheimer's disease (AD) and other neurodegenerative conditions. Sophora alopecuroides is widely used in traditional Uighur's medicine for the treatment of inflammation. Sophoraflavanone G (SG), a major flavonoid found in the S. alopecuroides, has also been reported to exhibit anti-inflammatory activity both in vitro and in vivo. However, the effect of S. alopecuroides and SG on microglia-mediated neuroinflammation has not been investigated...
December 1, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27814300/role-of-suppressor-of-cytokine-signaling-3-socs3-in-altering-activated-microglia-phenotype-in-appswe-ps1de9-mice
#18
Naotoshi Iwahara, Shin Hisahara, Jun Kawamata, Akihiro Matsumura, Kazuki Yokokawa, Taro Saito, Mai Fujikura, Tatsuo Manabe, Hiromi Suzuki, Takashi Matsushita, Syuuichirou Suzuki, Shun Shimohama
In response to changes of the central nervous system environment, microglia are capable of acquiring diverse phenotypes for cytotoxic or immune regulation and resolution of injury. Alzheimer's disease (AD) pathology also induces several microglial activations, resulting in production of pro-inflammatory cytokines and reactive oxygen species or clearance of amyloid-β (Aβ) through phagocytosis. We previously demonstrated that microglial activation and increase in oxidative stress started from the middle age in APPswe/PS1dE9 mice, and hypothesized that M1 activation occurs in middle-aged AD mice by Aβ stimulation...
November 3, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27813239/combined-tissue-and-fluid-proteomics-with-tandem-mass-tags-to-identify-low-abundant-protein-biomarkers-of-disease-in-peripheral-body-fluid-an-alzheimer-s-disease-case-study
#19
Claire L Russell, Amanda Heslegrave, Vikram Mitra, Henrik Zetterberg, Jennifer M Pocock, Malcolm A Ward, Ian Pike
RATIONALE: Ideal biomarkers are present in readily accessible samples including plasma and CSF, and are directly derived from diseased tissue, therefore likely to be of relatively low abundance. Traditional unbiased proteomic approaches for biomarker discovery have struggled to detect low abundance markers due to the high dynamic range of proteins, the predominance of hyper-abundant proteins, and the use of data-dependent acquisition MS. To overcome these limitations and improve biomarker discovery in peripheral fluids, we have developed TMTcalibrator™; a novel MS workflow combining isobarically labelled diseased tissue digests in parallel with an appropriate set of labelled body fluids to increase the chance of identifying low abundance, tissue-derived biomarkers...
November 4, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/27810377/preventive-effect-of-genetic-knockdown-and-pharmacological-blockade-of-cyslt1r-on-lipopolysaccharide-lps-induced-memory-deficit-and-neurotoxicity-in-vivo
#20
Fang Chen, Arijit Ghosh, Feng Wu, Susu Tang, Mei Hu, Hongbin Sun, Lingyi Kong, Hao Hong
Previously we reported that cysteinyl leukotrienes (Cys-LTs) and the type 1 receptor for Cys-LTs (CysLT1R) are related to amyloid β (Aβ)-induced neurotoxicity. The aim of the current study was to find out the role of CysLT1R on lipopolysaccharide (LPS)-induced cognitive deficit and neurotoxicity. shRNA-mediated knockdown or pharmacological blockade (by pranlukast) of CysLT1R were performed in ICR mice for 21days prior to systemic infusion of LPS. From day 22, LPS was administered for 7days and then a set of behavioral, histopathological and biochemical tests were employed to test memory, neuroinflammation and apoptotic responses in the mouse hippocampus...
November 1, 2016: Brain, Behavior, and Immunity
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