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https://www.readbyqxmd.com/read/28089846/modulation-of-neuroinflammation-and-pathology-in-the-5xfad-mouse-model-of-alzheimer-s-disease-using-a-biased-and-selective-beta-1-adrenergic-receptor-partial-agonist
#1
Pooneh Memar Ardestani, Andrew K Evans, Bitna Yi, Tiffany Nguyen, Laurence Coutellier, Mehrdad Shamloo
Degeneration of noradrenergic neurons occurs at an early stage of Alzheimer's Disease (AD). The noradrenergic system regulates arousal and learning and memory, and has been implicated in regulating neuroinflammation. Loss of noradrenergic tone may underlie AD progression at many levels. We have previously shown that acute administration of a partial agonist of the beta-1 adrenergic receptor (ADRB1), xamoterol, restores behavioral deficits in a mouse model of AD. The current studies examined the effects of chronic low dose xamoterol on neuroinflammation, pathology, and behavior in the pathologically aggressive 5XFAD transgenic mouse model of AD...
January 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28087694/iso-%C3%AE-acids-bitter-components-of-beer-prevent-inflammation-and-cognitive-decline-induced-in-a-mouse-model-of-alzheimer-s-disease
#2
Yasuhisa Ano, Atsushi Dhata, Yoshimasa Taniguchi, Ayaka Hoshi, Kazuyuki Uchida, Akihiko Takashima, Hiroyuki Nakayama
Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor (PPAR-γ). In normal mice, oral administration of iso-α-acids led to a significant increase both in CD11b and CD206 double-positive anti-inflammatory type microglia (P<0...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28078911/c5a-increases-the-injury-to-primary-neurons-elicited-by-fibrillar-amyloid-beta
#3
Michael X Hernandez, Pouya Namiranian, Eric Nguyen, Maria I Fonseca, Andrea J Tenner
C5aR1, the proinflammatory receptor for C5a, is expressed in the central nervous system on microglia, endothelial cells, and neurons. Previous work demonstrated that the C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in two Alzheimer's Disease (AD) mouse models. However, the cellular mechanisms of this protection have not been definitively demonstrated. Here, primary cultured mouse neurons treated with exogenous C5a show reproducible loss of MAP-2 staining in a dose-dependent manner within 24 hr of treatment, indicative of injury to neurons...
February 2017: ASN Neuro
https://www.readbyqxmd.com/read/28077724/trem2-promotes-microglial-survival-by-activating-wnt-%C3%AE-catenin-pathway
#4
Honghua Zheng, Lin Jia, Chia-Chen Liu, Zhouyi Rong Li Zhong, Longyu Yang, Xiao-Fen Chen, John D Fryer, Xin Wang, Yun-Wu Zhang, Huaxi Xu, Guojun Bu
: Triggering Receptor Expressed on Myeloid cells 2 (TREM2), expressed on myeloid cells including microglia in the central nervous system (CNS), has recently been identified as a risk factor for Alzheimer's disease (AD). TREM2 transmits intracellular signals through its trans-membrane binding partner DNAX-activating protein 12 (DAP12). Homozygous mutations inactivating TREM2 or DAP12 lead to Nasu-Hakola disease (NHD); however, how AD risk-conferring variants increase AD risk is not clear...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077703/app-modulates-a%C3%AE-induced-activation-of-microglia-in-mouse-model-of-alzheimer-s-disease
#5
Dibyadeep Datta
No abstract text is available yet for this article.
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28073379/tau-passive-immunization-inhibits-not-only-tau-but-also-a%C3%AE-pathology
#6
Chun-Ling Dai, Yunn Chyn Tung, Fei Liu, Cheng-Xin Gong, Khalid Iqbal
BACKGROUND: Accumulation of hyperphosphorylated tau protein is a histopathological hallmark of Alzheimer's disease (AD) and related tauopathies. Currently, there is no effective treatment available for these progressive neurodegenerative diseases. In recent years, tau immunotherapy has shown great potential in animal models. We report the effect of immunization with tau antibodies 43D against tau 6-18 and 77E9 against tau 184-195 on tau and amyloid-β (Aβ) pathologies and cognition in triple-transgenic (3×Tg)-AD mice at mild to moderate stages of the disease...
January 10, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28063055/isolation-of-microglia-and-immune-infiltrates-from-mouse-and-primate-central-nervous-system
#7
Thais F Galatro, Ilia D Vainchtein, Nieske Brouwer, Erik W G M Boddeke, Bart J L Eggen
Microglia are the innate immune cells of the central nervous system (CNS) and play an important role in the maintenance of tissue homeostasis, providing neural support and neuroprotection. Microglia constantly survey their environment and quickly respond to homeostatic perturbations. Microglia are increasingly implicated in neuropathological and neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, and glioma progression. Here, we describe a detailed isolation protocol for microglia and immune infiltrates, optimized for large amounts of post mortem tissue from human and rhesus macaque, as well as smaller tissue amounts from mouse brain and spinal cord, that yield a highly purified microglia population (up to 98 % purity)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28060896/isobavachalcone-attenuates-mptp-induced-parkinson-s-disease-in-mice-by-inhibition-of-microglial-activation-through-nf-%C3%AE%C2%BAb-pathway
#8
Haoran Jing, Shaoxia Wang, Min Wang, Wenliang Fu, Chao Zhang, Donggang Xu
Parkinson's disease (PD) is a complex multi-system and age-related neurodegenerative disorder. The intervention targeting neuroinflammation in PD patients is one effective strategy to slow down or inhibit disease progression. Microglia-mediated inflammatory response plays an important role in Parkinson's, Alzheimer's and other cerebral diseases. Isobavachalcone is a main component of Chinese herb medicine Psoralea corylifolia, which function includes immunoregulation, anti-oxidation and the regulation of β-amyloid (Aβ42) deposited in hippocampus in Alzheimer's patients...
2017: PloS One
https://www.readbyqxmd.com/read/28060279/quantitative-3d-in-silico-modeling-q3dism-of-cerebral-amyloid-beta-phagocytosis-in-rodent-models-of-alzheimer-s-disease
#9
Marie-Victoire Guillot-Sestier, Tara M Weitz, Terrence Town
Neuroinflammation is now recognized as a major etiological factor in neurodegenerative disease. Mononuclear phagocytes are innate immune cells responsible for phagocytosis and clearance of debris and detritus. These cells include CNS-resident macrophages known as microglia, and mononuclear phagocytes infiltrating from the periphery. Light microscopy has generally been used to visualize phagocytosis in rodent or human brain specimens. However, qualitative methods have not provided definitive evidence of in vivo phagocytosis...
December 26, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28054940/neuroprotective-effects-of-aged-garlic-extract-on-cognitive-dysfunction-and-neuroinflammation-induced-by-%C3%AE-amyloid-in-rats
#10
Nutchareeporn Nillert, Wanassanun Pannangrong, Jariya Umka Welbat, Wunnee Chaijaroonkhanarak, Kittisak Sripanidkulchai, Bungorn Sripanidkulchai
Neuroinflammation is pathological evidence of Alzheimer's disease (AD) that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ) deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), which may lead to neuronal damage and eventual death. Aged garlic extract (AGE) has been reported to have multiple biological activities, including anti-inflammatory effects...
January 3, 2017: Nutrients
https://www.readbyqxmd.com/read/28053038/large-soluble-oligomers-of-amyloid-%C3%AE-protein-from-alzheimer-brain-are-far-less-neuroactive-than-the-smaller-oligomers-to-which-they-dissociate
#11
Ting Yang, Shaomin Li, Huixin Xu, Dominic M Walsh, Dennis J Selkoe
: Soluble oligomers of amyloid β-protein (oAβ) isolated from the brains of Alzheimer's disease (AD) patients have been shown experimentally (in the absence of amyloid plaques) to impair hippocampal synaptic plasticity, decrease synapses, induce tau hyperphosphorylation and neuritic dystrophy, activate microglial inflammation, and impair memory in normal adult rodents. Nevertheless, there has been controversy about what types of oligomers actually confer these AD-like phenotypes. Here, we show that the vast majority of soluble Aβ species obtained from brains of humans who died with confirmed AD elute at high molecular weight (HMW) on nondenaturing size-exclusion chromatography...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28039950/ageing-causes-prominent-neurovascular-dysfunction-associated-with-loss-of-astrocytic-contacts-and-gliosis
#12
Jessica Duncombe, Ross J Lennen, Maurits A Jansen, Ian Marshall, Joanna M Wardlaw, Karen Horsburgh
AIMS: Normal neurovascular coupling, mediated by the fine interplay and communication of cells within the neurovascular unit, is critical for maintaining normal brain activity and cognitive function. This study investigated whether, with advancing age there is disruption of neurovascular coupling and specific cellular components of the neurovascular unit, and whether the effects of increasing amyloid (a key feature of Alzheimer's disease) would exacerbate these changes. METHODS: Wild-type mice, in which amyloid deposition is absent, were compared to transgenic APP littermates (TgSwDI) which develop age-dependent increases in amyloid...
December 31, 2016: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28039536/cardiolipin-in-central-nervous-system-physiology-and-pathology
#13
REVIEW
Caitlin B Pointer, Andis Klegeris
Cardiolipin, an anionic phospholipid found primarily in the inner mitochondrial membrane, has many well-defined roles within the peripheral tissues, including the maintenance of mitochondrial membrane fluidity and the regulation of mitochondrial functions. Within the central nervous system (CNS), cardiolipin is found within both neuronal and non-neuronal glial cells, where it regulates metabolic processes, supports mitochondrial functions, and promotes brain cell viability. Furthermore, cardiolipin has been shown to act as an elimination signal and participate in programmed cell death by apoptosis of both neurons and glia...
December 30, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28039031/worsening-of-memory-deficit-induced-by-energy-dense-diet-in-a-rat-model-of-early-alzheimer-s-disease-is-associated-to-neurotoxic-a%C3%AE-species-and-independent-of-neuroinflammation
#14
Pamela V Martino Adami, Pablo Galeano, Marina L Wallinger, Celia Quijano, Alejandro Rabossi, Eleonora S Pagano, Natividad Olivar, Carlos Reyes Toso, Daniel Cardinali, Luis I Brusco, Sonia Do Carmo, Rafael Radi, Goar Gevorkian, Eduardo M Castaño, A Claudio Cuello, Laura Morelli
Diet is a modifiable risk factor for Alzheimer's disease (AD), but the mechanisms linking alterations in peripheral metabolism and cognition remain unclear. Since it is especially difficult to study long-term effects of high-energy diet in individuals at risk for AD, we addressed this question by using the McGill-R-Thy1-APP transgenic rat model (Tg(+/-)) that mimics presymptomatic AD. Wild-type and Tg(+/-) rats were exposed during 6months to a standard diet or a Western diet (WD), high in saturated fat and sugar...
December 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28035965/anti-neuroinflammatory-ent-kaurane-diterpenoids-from-pteris-multifida-roots
#15
Jung Wha Kim, Ji Yeon Seo, Won Keun Oh, Sang Hyun Sung
Activated microglia are known to be a major source of cellular neuroinflammation which causes various neurodegenerative diseases, including Alzheimer's disease. In our continuing efforts to search for new bioactive phytochemicals against neuroinflammatory diseases, the 80% methanolic extract of Pteris multifida (Pteridaceae) roots was found to exhibit significant NO inhibitory activity in lipopolysaccharide (LPS)-activated BV-2 microglia cells. Three new ent-kaurane diterpenoids, pterokaurane M₁ 2-O-β-d-glucopyranoside (4), 2β,16α-dihydroxy-ent-kaurane 2,16-di-O-β-d-glucopyranoside (10), and 2β,16α,17-trihydroxy-ent-kaurane 2-O-β-d-glucopyranoside (12), were isolated along with nine other known compounds from P...
December 26, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28027926/early-life-stress-lastingly-alters-the-neuroinflammatory-response-to-amyloid-pathology-in-an-alzheimer-s-disease-mouse-model
#16
Lianne Hoeijmakers, Silvie R Ruigrok, Anna Amelianchik, Daniela Ivan, Anne-Marie van Dam, Paul J Lucassen, Aniko Korosi
Exposure to stress during the sensitive period of early-life increases the risk to develop cognitive impairments and psychopathology later in life. In addition, early-life stress (ES) exposure, next to genetic causes, has been proposed to modulate the development and progression of Alzheimer's disease (AD), however evidence for this hypothesis is currently lacking. We here tested whether ES modulates progression of AD-related neuropathology and assessed the possible contribution of neuroinflammatory factors in this...
December 24, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28009077/inflammasomes-as-therapeutic-targets-for-alzheimer-s-disease
#17
Claire S White, Catherine B Lawrence, David Brough, Jack Rivers-Auty
Alzheimer's disease is the most common form of progressive dementia, typified initially by short term memory deficits which develop into a dramatic global cognitive decline. The classical hall marks of Alzheimer's disease include the accumulation of amyloid oligomers and fibrils, and the intracellular formation of neurofibrillary tangles of hyperphosphorylated tau. It is now clear that inflammation also plays a central role in the pathogenesis of the disease through a number of neurotoxic mechanisms. Microglia are the key immune regulators of the CNS which detect amyloidopathy through cell surface and cytosolic pattern recognition receptors (PRRs) and respond by initiating inflammation through the secretion of cytokines such as interleukin-1β (IL-1β)...
December 23, 2016: Brain Pathology
https://www.readbyqxmd.com/read/28007893/young-microglia-restore-amyloid-plaque-clearance-of-aged-microglia
#18
Anna Daria, Alessio Colombo, Gemma Llovera, Heike Hampel, Michael Willem, Arthur Liesz, Christian Haass, Sabina Tahirovic
Alzheimer's disease (AD) is characterized by deposition of amyloid plaques, neurofibrillary tangles, and neuroinflammation. In order to study microglial contribution to amyloid plaque phagocytosis, we developed a novel ex vivo model by co-culturing organotypic brain slices from up to 20-month-old, amyloid-bearing AD mouse model (APPPS1) and young, neonatal wild-type (WT) mice. Surprisingly, co-culturing resulted in proliferation, recruitment, and clustering of old microglial cells around amyloid plaques and clearance of the plaque halo...
December 21, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28004107/humulus-japonicus-inhibits-the-progression-of-alzheimer-s-disease-in-a-app-ps1-transgenic-mouse-model
#19
Tae-Shin Park, Young-Kyoung Ryu, Hye-Yeon Park, Jae Yun Kim, Jun Go, Jung-Ran Noh, Yong-Hoon Kim, Jung Hwan Hwang, Dong-Hee Choi, Won-Keun Oh, Chul-Ho Lee, Kyoung-Shim Kim
Humulus japonicus Siebold & Zucc. (HJ) has traditionally been administered to patients with pulmonary disease, skin disease and hypertension in Korea, and it is considered to exert anti-inflammatory, antioxidant, antimicrobial and antimycobacterial effects. However, its effects against Alzheimer's disease (AD) have yet to be explored. Thus, this study was carried out to investigate whether HJ has a beneficial effect on the progression of AD in an animal model. A methanolic extract of HJ (500 mg/kg/day) was intragastrically administered to 5-month-old APP/PS1 transgenic (Tg-APP/PS1) mice for 2...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28003160/regulatory-factor-x1-depresses-apoe-dependent-a%C3%AE-uptake-by-mirna-124-in-microglial-response-to-oxidative-stress
#20
Chen-Zhuo Feng, Jin-Bo Yin, Jian-Jun Yang, Lin Cao
Decreased proteolytic clearance of soluble amyloid β (Aβ) in microglia affects Aβ accumulation on Alzheimer's disease progression. However, the potential molecular mechanism by which microglial Aβ uptake is regulated remains unclear. In this study, we identified a microRNA, miR-124, that was down-regulated in aging with a function in regulating apolipoprotein E (ApoE)-dependent Aβ uptake by targeting regulatory factor X1 (RFX1) transcripts on BV2 microglia cell. Decreased expression of miRNA-124 in BV2 cells exposed to mild hydrogen peroxide increased RFX1 protein level and decreased the expression of ApoE, a gene which has been suggested to enhance cellular Aβ uptake in microglia...
December 18, 2016: Neuroscience
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