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Microglia alzheimer's disease

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https://www.readbyqxmd.com/read/28646899/immunoproteasome-deficiency-alters-microglial-cytokine-response-and-improves-cognitive-deficits-in-alzheimer-s-disease-like-appps1-mice
#1
Lisa K Wagner, Kate E Gilling, Eileen Schormann, Peter M Kloetzel, Frank L Heppner, Elke Krüger, Stefan Prokop
The immunoproteasome (iP) represents a specialized type of proteasomes, which plays an important role in the clearance of oxidant-damaged proteins under inflammatory and pathological conditions determining the outcome of various diseases. In Alzheimer's disease (AD)-like APPPS1 mice Aβ-deposition is paralleled by iP upregulation, most likely mediated through type I interferon induction. To define the impact of increased iP expression we crossed APPPS1 mice with mice deficient in the iP subunit LMP7 resulting in impaired iP function...
June 24, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28643422/microglia-targeted-stem-cell-therapies-for-alzheimer-disease-a-preclinical-data-review
#2
REVIEW
Zhiwei Shen, Xueyuan Li, Xinjie Bao, Renzhi Wang
Alzheimer disease (AD) is a severe, life-threatening illness characterized by gradual memory loss. The classic histological features of AD include extracellular formation of β-amyloid plaques (Aβ), intracellular neurofibrillary tangles (NFT), and synaptic loss. Recently, accumulated evidence has confirmed the critical role of microglia in the development and exacerbation of AD. When Aβ forms deposits, microglia quickly respond to restore brain physiology by activating a series of repair mechanisms. However, prolonged microglial activation is considered detrimental and may aggravate AD progression...
June 23, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28640632/gut-microbiota-nitric-oxide-and-microglia-as-pre-requisites-for-neurodegenerative-disorders
#3
Joyce Ka Yu Tse
Regulating fluctuating endogenous nitric oxide (NO) levels is necessary for proper physiological functions. Aberrant NO pathways are implicated in a number of neurological disorders, including Alzheimer's Disease (AD) and Parkinson's Disease. The mechanism of NO in oxidative and nitrosative stress with pathological consequences involves reactions with reactive oxygen species (e.g. superoxide) to form the highly reactive peroxynitrite, hydrogen peroxide, hypochloride ions and hydroxyl radical. NO levels are typically regulated by endogenous nitric oxide synthases (NOS), and inflammatory iNOS is implicated in the pathogenesis of neurodegenerative diseases, in which elevated NO mediates axonal degeneration and activates cyclooxygenases to provoke neuroinflammation...
June 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28638339/nutritional-and-pharmacological-strategies-to-regulate-microglial-polarization-in-cognitive-aging-and-alzheimer-s-disease
#4
REVIEW
Emiliano Peña-Altamira, Sabrina Petralla, Francesca Massenzio, Marco Virgili, Maria L Bolognesi, Barbara Monti
The study of microglia, the immune cells of the brain, has experienced a renaissance after the discovery of microglia polarization. In fact, the concept that activated microglia can shift into the M1 pro-inflammatory or M2 neuroprotective phenotypes, depending on brain microenvironment, has completely changed the understanding of microglia in brain aging and neurodegenerative diseases. Microglia polarization is particularly important in aging since an increased inflammatory status of body compartments, including the brain, has been reported in elderly people...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28637381/role-of-caspase-3-mediated-apoptosis-in-chronic-caspase-3-cleaved-tau-accumulation-and-blood-brain-barrier-damage-in-the-corpus-callosum-after-traumatic-brain-injury-in-rats
#5
Olena Glushakova, Andriy O Glushakov, Cesar Borlongan, Alex Valadka, Ronald L Hayes, Alexander V Glushakov
Traumatic brain injury (TBI) may be a significant risk factor for development of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE), post-traumatic epilepsy (PTE), and Alzheimer's (AD) and Parkinson's (PD) diseases. Chronic TBI is associated with several pathological features that are also characteristic of neurodegenerative diseases, including tau pathologies, caspase-3-mediated apoptosis, neuroinflammation, and microvascular alterations. The goal of this study was to evaluate changes following TBI in cleaved-caspase-3 and caspase-3-cleaved tau truncated at Asp421 and their relationships to cellular markers potentially associated with inflammation and blood-brain (BBB) barrier damage...
June 22, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28637354/essential-dietary-bioactive-lipids-in-neuroinflammatory-diseases
#6
M Valeria Catani, Valeria Gasperi, Tiziana Bisogno, Mauro Maccarrone
Under physiological conditions, neurons and glia are in a healthy, redox-balanced environment; when injury perturbs this equilibrium, a neuroinflammatory state is established by activated microglia that triggers pro-inflammatory responses and alters the oxidant/antioxidant balance, thus leading to neuronal loss and neurodegeneration. In neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease, amyothrophic lateral sclerosis, and multiple sclerosis), the brain is in a constitutively self-sustaining cycle of inflammation and oxidative stress that prompts and amplifies brain damage...
June 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28628896/cholinergic-neuron-gene-expression-differences-captured-by-translational-profiling-in-a-mouse-model-of-alzheimer-s-disease
#7
Paul M McKeever, TaeHyung Kim, Andrew R Hesketh, Laura MacNair, Denise Miletic, Giorgio Favrin, Stephen G Oliver, Zhaolei Zhang, Peter St George-Hyslop, Janice Robertson
Cholinergic neurotransmission is impaired in Alzheimer's disease (AD), and loss of basal forebrain cholinergic neurons is a key component of disease pathogenicity and symptomatology. To explore the molecular basis of this cholinergic dysfunction, we paired translating ribosome affinity purification (TRAP) with RNA sequencing (TRAP-Seq) to identify the actively translating mRNAs in anterior forebrain cholinergic neurons in the TgCRND8 mouse model of AD. Bioinformatic analyses revealed the downregulation of 67 of 71 known cholinergic-related transcripts, consistent with cholinergic neuron dysfunction in TgCRND8 mice, as well as transcripts related to oxidative phosphorylation, neurotrophins, and ribosomal processing...
May 25, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28624505/deficiency-in-ep4-receptor-associated-protein-ameliorates-abnormal-anxiety-like-behavior-and-brain-inflammation-in-a-mouse-model-of-alzheimer-disease
#8
Risako Fujikawa, Sei Higuchi, Masato Nakatsuji, Mika Yasui, Taichi Ikedo, Manabu Nagata, Kosuke Hayashi, Masayuki Yokode, Manabu Minami
Microglia are thought to play key roles in the progression of Alzheimer disease (AD). Overactivated microglia produce proinflammatory cytokines, such as tumor necrosis factor-α, which appear to contribute to disease progression. Previously, we reported that prostaglandin E2 type 4 receptor-associated protein (EPRAP) promotes microglial activation. We crossed human amyloid precursor protein transgenic mice from strain J20(+/-) onto an EPRAP-deficient background to determine the role of EPRAP in AD. Behavioral tests were performed in 5-month-old male J20(+/-)EPRAP(+/+) and J20(+/-)EPRAP(-/-) mice...
June 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28623716/aldose-reductase-inhibitors-attenuate-%C3%AE-amyloid-induced-tnf-%C3%AE-production-in-microlgia-via-ros-pkc-mediated-nf-%C3%AE%C2%BAb-and-mapk-pathways
#9
Xiao-Min Song, Qian Yu, Xin Dong, Hyun Ok Yang, Ke-Wu Zeng, Jun Li, Peng-Fei Tu
Microglia-mediated neuroinflammation is a key risk factor to the development of Alzheimer' disease (AD). Aldose reductase (AR) has been found to be widely involved in inflammation-related diseases; however, whether aldose reductase inhibitors (ARIs) could be used to treat neuroinflammation is rarely reported. This study aims to evaluate the anti-neuroinflammatory effects of two major ARIs of Sorbinil (Sor) and Zopolrestat (Zol) in β-amyloid protein (Aβ)-induced microglia (BV-2). We find that Sor and Zol significantly inhibit TNF-α, IL-1β, IL-6 production from microglia in response to Aβ stimulation...
June 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28622503/damed-in-trem-2-steps
#10
Sandro Da Mesquita, Jonathan Kipnis
The role of microglia in neurodegenerative diseases has been controversial. In this issue, Keren-Shaul et al. identify a unique population of disease-associated microglia (DAM) that develop in two steps and may help to restrict damage in Alzheimer and related diseases.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28618077/generation-of-a-microglial-developmental-index-in-mice-and-in-humans-reveals-a-sex-difference-in-maturation-and-immune-reactivity
#11
Richa Hanamsagar, Mark D Alter, Carina S Block, Haley Sullivan, Jessica L Bolton, Staci D Bilbo
Evidence suggests many neurological disorders emerge when normal neurodevelopmental trajectories are disrupted, i.e., when circuits or cells do not reach their fully mature state. Microglia play a critical role in normal neurodevelopment and are hypothesized to contribute to brain disease. We used whole transcriptome profiling with Next Generation sequencing of purified developing microglia to identify a microglial developmental gene expression program involving thousands of genes whose expression levels change monotonically (up or down) across development...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28612290/deficiency-of-tyrobp-an-adapter-protein-for-trem2-and-cr3-receptors-is-neuroprotective-in-a-mouse-model-of-early-alzheimer-s-pathology
#12
Jean-Vianney Haure-Mirande, Mickael Audrain, Tomas Fanutza, Soong Ho Kim, William L Klein, Charles Glabe, Ben Readhead, Joel T Dudley, Robert D Blitzer, Minghui Wang, Bin Zhang, Eric E Schadt, Sam Gandy, Michelle E Ehrlich
Conventional genetic approaches and computational strategies have converged on immune-inflammatory pathways as key events in the pathogenesis of late onset sporadic Alzheimer's disease (LOAD). Mutations and/or differential expression of microglial specific receptors such as TREM2, CD33, and CR3 have been associated with strong increased risk for developing Alzheimer's disease (AD). DAP12 (DNAX-activating protein 12)/TYROBP, a molecule localized to microglia, is a direct partner/adapter for TREM2, CD33, and CR3...
June 13, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28611577/the-anti-inflammatory-effects-of-lipoxygenase-and-cyclo-oxygenase-inhibitors-in-inflammation-induced-human-fetal-glia-cells-and-the-a%C3%AE-degradation-capacity-of-human-fetal-astrocytes-in-an-ex-vivo-assay
#13
Rea Pihlaja, Merja Haaparanta-Solin, Juha O Rinne
Chronic inflammation is a common phenomenon present in the background of multiple neurodegenerative diseases, including Alzheimer's disease (AD). The arachidonic acid pathway overproduces proinflammatory eicosanoids during these states and glial cells in the brain gradually lose their vital functions of protecting and supporting neurons. In this study, the role of different key enzymes of the eicosanoid pathway mediating inflammatory responses was examined in vitro and ex vivo using human fetal glial cells...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28611242/evaluation-of-%C3%AE-pet-outcome-measures-to-detect-disease-modification-induced-by-bace-inhibition-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#14
Steven Deleye, Ann Marie Waldron, Jeroen Verhaeghe, Astrid Bottelbergs, Leonie Wyffels, Bianca Van Broeck, Xavier Langlois, Mark E Schmidt, Sigrid Stroobants, Steven Staelens
Purpose: In this study, we investigated the effects of chronic administration of an inhibitor of the β-site amyloid precursor protein -cleaving enzyme 1 (BACE1) on Alzheimer's- related pathology by multi-tracer positron emission tomography (PET) imaging in APPPS1-21 mice. Methods: Wild-type (WT) and APPPS1-21 (TG) mice received vehicle (VEH) or BACE inhibitor (60 mg/kg) initiated at 7 weeks of age. Outcome measures of brain metabolism, neuroinflammation and amyloid-β pathology were obtained through μPET imaging with (18)F-FDG, (18)F-PBR111 and (18)F-AV45 respectively...
June 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28610747/cathepsin-b-plays-a-critical-role-in-inducing-alzheimer-s-disease-like-phenotypes-following-chronic-systemic-exposure-to-lipopolysaccharide-from-porphyromonas-gingivalis-in-mice
#15
Zhou Wu, Junjun Ni, Yicong Liu, Jessica L Teeling, Fumiko Takayama, Alex Collcutt, Paul Ibbett, Hiroshi Nakanishi
A number of clinical and experimental studies have revealed a strong association between periodontitis and accelerated cognitive decline in Alzheimer's disease (AD); however, the mechanism of the association is unknown. In the present study, we tested the hypothesis that cathepsin (Cat) B plays a critical role in the initiation of neuroinflammation and neural dysfunction following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (PgLPS) in mice (1mg/kg, daily, intraperitoneally)...
June 10, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28606182/microglia-limit-the-expansion-of-%C3%AE-amyloid-plaques-in-a-mouse-model-of-alzheimer-s-disease
#16
Ruohe Zhao, Wanling Hu, Julia Tsai, Wei Li, Wen-Biao Gan
BACKGROUND: Microglia are known as resident immune cells in the brain. β-amyloid (Aβ) plaques in the brain of Alzheimer's disease (AD) are surrounded by microglia, but whether and how microglia affect the formation and maintenance of plaques remains controversial. METHODS: We depleted microglia by injecting diphtheria toxin (DT) in CX 3 CR1 (CreER/+) :R26 (DTR/+) (CX 3 CR1-iDTR) mice crossed with APPswe/PSEN1dE9 (APP/PS1) mice. Intravital time-lapse imaging was performed to examine changes in the number and size of Congo Red-labeled amyloid plaques over 1-2 weeks...
June 12, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28602351/a-unique-microglia-type-associated-with-restricting-development-of-alzheimer-s-disease
#17
Hadas Keren-Shaul, Amit Spinrad, Assaf Weiner, Orit Matcovitch-Natan, Raz Dvir-Szternfeld, Tyler K Ulland, Eyal David, Kuti Baruch, David Lara-Astaiso, Beata Toth, Shalev Itzkovitz, Marco Colonna, Michal Schwartz, Ido Amit
Alzheimer's disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, defining the roles of immune cell subsets in AD onset and progression has been challenging. Using transcriptional single-cell sorting, we comprehensively map all immune populations in wild-type and AD-transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify markers, spatial localization, and pathways associated with these cells...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28601280/staining-of-hla-dr-iba1-and-cd68-in-human-microglia-reveals-partially-overlapping-expression-depending-on-cellular-morphology-and-pathology
#18
Debbie A E Hendrickx, Corbert G van Eden, Karianne G Schuurman, Jörg Hamann, Inge Huitinga
HLA-DR, Iba1 and CD68 are widely used microglia markers in human tissue. However, due to differences in gene regulation, they may identify different activation stages of microglia. Here, we directly compared the expression of HLA-DR, Iba1 and CD68 in microglia with different phenotypes, ranging from ramified to amoeboid, to foamy phagocytizing macrophages, in adjacent sections immunocytochemically double stained for two of the markers. Material was used from patients diagnosed with multiple sclerosis (MS) and Alzheimer's disease (AD) patients and control subjects because together they contain all the microglia activation stages in an acute and a chronic inflammatory setting...
August 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28596835/chronic-diazepam-administration-increases-the-expression-of-lcn2-in-the-cns
#19
Tomonori Furukawa, Shuji Shimoyama, Yasuo Miki, Yoshikazu Nikaido, Kohei Koga, Kazuhiko Nakamura, Koichi Wakabayashi, Shinya Ueno
Benzodiazepines (BZDs), which bind with high affinity to gamma-aminobutyric acid type A receptors (GABAA-Rs) and potentiate the effects of GABA, are widely prescribed for anxiety, insomnia, epileptic discharge, and as anticonvulsants. The long-term use of BZDs is limited due to adverse effects such as tolerance, dependence, withdrawal effects, and impairments in cognition and learning. Additionally, clinical reports have shown that chronic BZD treatment increases the risk of Alzheimer's disease. Unusual GABAA-R subunit expression and GABAA-R phosphorylation are induced by chronic BZD use...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28595078/amyloidogenic-proteins-associated-with-neurodegenerative-diseases-activate-the-nlrp3-inflammasome
#20
REVIEW
Qian-Hang Shao, Xiao-Ling Zhang, Peng-Fei Yang, Yu-He Yuan, Nai-Hong Chen
Neuroinflammation has been shown as an essential factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and Multiple Sclerosis. Furthermore, activated microglia and increased pro-inflammatory cytokines are the major hallmarks in neurodegenerative diseases. A multimolecular complex named as inflammasome is involved in the process of inflammatory response, which can activate inflammatory caspases, leading to the cleavage and secretion of inflammatory cytokines, and finally generates a potent inflammatory response...
June 5, 2017: International Immunopharmacology
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