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Mouse modell for alzheimers disease

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https://www.readbyqxmd.com/read/28106772/neuroprotective-and-anti-apoptotic-effects-of-csp-1103-in-primary-cortical-neurons-exposed-to-oxygen-and-glucose-deprivation
#1
Vanessa Porrini, Ilenia Sarnico, Marina Benarese, Caterina Branca, Mariana Mota, Annamaria Lanzillotta, Arianna Bellucci, Edoardo Parrella, Lara Faggi, Pierfranco Spano, Bruno Pietro Imbimbo, Marina Pizzi
CSP-1103 (formerly CHF5074) has been shown to reverse memory impairment and reduce amyloid plaque as well as inflammatory microglia activation in preclinical models of Alzheimer's disease. Moreover, it was found to improve cognition and reduce brain inflammation in patients with mild cognitive impairment. Recent evidence suggests that CSP-1103 acts through a single molecular target, the amyloid precursor protein intracellular domain (AICD), a transcriptional regulator implicated in inflammation and apoptosis...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106556/an-improved-drugs-screening-system-reveals-that-baicalein-ameliorates-the-a%C3%AE-ampa-nmda-induced-depolarization-of-neurons
#2
Tian-Syuan Lin, Han-Jung Tsai, Chih-Han Lee, Yan-Qing Song, Rih-Sheng Huang, Hsiu-Mei Hsieh-Li, Mei-Chih Liang, Yenshou Lin
The presence of amyloid-β (Aβ) plaque and tau protein hyperphosphorylation in brain tissue is the pathological hallmark of Alzheimer's disease (AD). At least some Aβ neurotoxicity is caused by the presence of excess glutamate that has been induced by Aβ accumulation. Memantine is currently the only NMDA receptor inhibitor approved for treating moderate-to-severe AD patients. We utilized primary cortical neurons and DiBAC4(3), a slow-response voltage sensitive fluorescence dye, to create a novel system for screening herbal medicines that allows the identification of pure compounds able to ameliorate Aβ-induced abnormal depolarization...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106117/norovirus-p-particle-based-active-a%C3%AE-immunotherapy-elicits-sufficient-immunogenicity-and-improves-cognitive-capacity-in-a-mouse-model-of-alzheimer-s-disease
#3
Lu Fu, Yingnan Li, Yue Hu, Yayuan Zheng, Bin Yu, Haihong Zhang, Jiaxin Wu, Hui Wu, Xianghui Yu, Wei Kong
Disease-modifying immunotherapies focusing on reducing amyloid-beta (Aβ) deposition are the main treatment for Alzheimer's disease (AD). However, none of the Aβ immunotherapies has produced clinically meaningful results to date. The main reason for this lack of efficacy is that the vaccine induces insufficiently high antibody titers, as it contains small B-cell epitope of Aβ to avoid Aβ42-specific T-cell activation. With the aim of generating a potent AD vaccine, we designed the protein PP-3copy-Aβ1-6-loop123, comprising three copies of Aβ1-6 inserted into three loops of a novel vaccine platform, the norovirus P particle, which could present Aβ at its surface and remarkably enhance the immunogenicity of the vaccine...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28103298/perinatal-choline-supplementation-reduces-amyloidosis-and-increases-choline-acetyltransferase-expression-in-the-hippocampus-of-the-appsweps1de9-alzheimer-s-disease-model-mice
#4
Tiffany J Mellott, Olivia M Huleatt, Bethany N Shade, Sarah M Pender, Yi B Liu, Barbara E Slack, Jan K Blusztajn
Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT) female mice with hemizygous APPswe/PS1dE9 (APP.PS1) AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1...
2017: PloS One
https://www.readbyqxmd.com/read/28100745/disease-progression-dependent-effects-of-trem2-deficiency-in-a-mouse-model-of-alzheimer-s-disease
#5
Taylor R Jay, Anna M Hirsch, Margaret L Broihier, Crystal M Miller, Lee E Neilson, Richard M Ransohoff, Bruce T Lamb, Gary E Landreth
: Neuroinflammation is an important contributor to Alzheimer's disease (AD) pathogenesis, as underscored by the recent identification of immune-related genetic risk factors for AD, including coding variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2). Understanding TREM2 function promises to provide important insights into how neuroinflammation contributes to AD pathology. However, studies so far have produced seemingly conflicting results, with reports that amyloid pathology can be both decreased and increased in TREM2-deficient AD mouse models...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28099989/effects-of-a-dietary-ketone-ester-on-hippocampal-glycolytic-and-tca-cycle-intermediates-and-amino-acids-in-a-3xtgad-mouse-model-of-alzheimer-s-disease
#6
Robert J Pawlosky, Martin F Kemper, Yoshihero Kashiwaya, M Todd King, Mark P Mattson, Richard L Veech
In patients with Alzheimer's disease (AD) and in a triple transgenic (3xTgAD) mouse model of AD low glucose metabolism in the brain precedes loss of memory and cognitive decline. The metabolism of ketones in the brain by-passes glycolysis and therefore may correct several deficiencies that are associated with glucose hypometabolism. A dietary supplement composed of an ester of D-β-hydroxybutyrate and R-1,3 butane diol referred to as ketone ester (KE) was incorporated into a rodent diet and fed to 3xTgAD mice for 8 months...
January 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28096851/acetylcholinesterase-inhibitor-improves-learning-and-memory-impairment-induced-by-toxoplasma-gondii-infection
#7
Hossein Mahmoudvand, Vahid Sheibani, Hossein Keshavarz, Saeedeh Shojaee, Khadijeh Esmaeelpour, Naser Ziaali
BACKGROUND: Here, we established the mouse models of chronic toxoplasmosis by T. gondii Tehran strain to provide a good understanding about defining the possible association between T. gondii exposure and learning and memory impairments. Moreover, as secondary objective of the present study, we hypothesized whether administration of an acetylcholinesterase (AChE) inhibitor could reduce learning and memory impairments induced by T. gondii infection. METHODS: Twenty-four male BALB/c mice were used to establishment of latent toxoplasmosis...
April 2016: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/28096242/developing-therapeutics-for-prp-prion-diseases
#8
Kurt Giles, Steven H Olson, Stanley B Prusiner
The prototypical PrP prion diseases are invariably fatal, and the search for agents to treat them spans more than 30 years, with limited success. However, in the last few years, the application of high-throughput screening, medicinal chemistry, and pharmacokinetic optimization has led to important advances. The PrP prion inoculation paradigm provides a robust assay for testing therapeutic efficacy, and a dozen compounds have been reported that lead to meaningful extension in survival of prion-infected mice...
January 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28094952/effect-of-an-enhanced-nose-to-brain-delivery-of-insulin-on-mild-and-progressive-memory-loss-in-the-senescence-accelerated-mouse
#9
Noriyasu Kamei, Misa Tanaka, Hayoung Choi, Nobuyuki Okada, Takamasa Ikeda, Rei Itokazu, Mariko Takeda-Morishita
Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28091722/hyperphosphorylated-tau-causes-reduced-hippocampal-ca1-excitability-by-relocating-the-axon-initial-segment
#10
Robert John Hatch, Yan Wei, Di Xia, Jürgen Götz
Hyperphosphorylated tau has a critical role in tauopathies such as Alzheimer's disease and frontotemporal dementia, impairing neuronal function and eventually leading to neurodegeneration. A critical role for tau is supported by studies in transgenic mouse models that express the P301L tau mutation found in cases of familial frontotemporal dementia, with the accumulation of hyperphosphorylated tau in the hippocampus causing reductions in hippocampal long-term potentiation and impairments in spatial learning and memory...
January 16, 2017: Acta Neuropathologica
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
#11
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
#12
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/28079060/intranasal-lactoferrin-enhances-%C3%AE-secretase-dependent-amyloid-precursor-protein-processing-via-the-erk1-2-creb-and-hif-1%C3%AE-pathways-in-an-alzheimer-s-disease-mouse-model
#13
Chuang Guo, Zhao-Hui Yang, Shuai Zhang, Rui Chai, Han Xue, Yan-Hui Zhang, Jia-Yi Li, Zhan-You Wang
Growing evidence suggests that lactoferrin (Lf), an iron-binding glycoprotein, is a pleiotropic functional nutrient. Additionally, Lf was recently implicated as a neuroprotective agent. These properties make Lf a valuable therapeutic candidate for the treatment of Alzheimer's disease (AD). However, the mechanisms regulating the physiological roles of Lf in the pathologic condition of AD remain unknown. In the present study, an APPswe/PS1DE9 transgenic mouse model of AD was used. We explored whether intranasal human Lf (hLf) administration could reduce β-amyloid (Aβ) deposition and ameliorate cognitive decline in this AD model...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28078911/c5a-increases-the-injury-to-primary-neurons-elicited-by-fibrillar-amyloid-beta
#14
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
#15
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/28076758/polysaccharides-from-ganoderma-lucidum-promote-cognitive-function-and%C3%A2-neural-progenitor-proliferation-in-mouse-model-of-alzheimer-s-disease
#16
Shichao Huang, Jianxin Mao, Kan Ding, Yue Zhou, Xianglu Zeng, Wenjuan Yang, Peipei Wang, Cun Zhao, Jian Yao, Peng Xia, Gang Pei
Promoting neurogenesis is a promising strategy for the treatment of cognition impairment associated with Alzheimer's disease (AD). Ganoderma lucidum is a revered medicinal mushroom for health-promoting benefits in the Orient. Here, we found that oral administration of the polysaccharides and water extract from G. lucidum promoted neural progenitor cell (NPC) proliferation to enhance neurogenesis and alleviated cognitive deficits in transgenic AD mice. G. lucidum polysaccharides (GLP) also promoted self-renewal of NPC in cell culture...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28073379/tau-passive-immunization-inhibits-not-only-tau-but-also-a%C3%AE-pathology
#17
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/28072877/motor-cortex-theta-and-gamma-architecture-in-young-adult-appsweps1de9-alzheimer-mice
#18
Anna Papazoglou, Julien Soos, Andreas Lundt, Carola Wormuth, Varun Raj Ginde, Ralf Müller, Christina Henseler, Karl Broich, Kan Xie, Britta Haenisch, Dan Ehninger, Marco Weiergräber
Alzheimer's disease (AD) is a multifactorial disorder leading to progressive memory loss and eventually death. In this study, an APPswePS1dE9 AD mouse model has been analyzed for motor cortex theta, beta and gamma frequency alterations using computerized 3D stereotaxic electrode positioning and implantable video-EEG radiotelemetry to perform long-term M1 recordings from both genders considering age, circadian rhythm and activity status of experimental animals. We previously demonstrated that APPswePS1dE9 mice exibit complex alterations in hippocampal frequency power and another recent investigation reported a global increase of alpha, beta and gamma power in APPswePS1dE9 in females of 16-17 weeks of age...
2017: PloS One
https://www.readbyqxmd.com/read/28072821/maysin-and-its-flavonoid-derivative-from-centipedegrass-attenuates-amyloid-plaques-by-inducting-humoral-immune-response-with-th2-skewed-cytokine-response-in-the-tg-appswe-ps1de9-alzheimer-s-mouse-model
#19
Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Hyoung-Woo Bai, Seung Sik Lee, SungBeom Lee, Byung Yeoup Chung, Jae-Hyeon Cho
Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models...
2017: PloS One
https://www.readbyqxmd.com/read/28070672/opposing-effects-of-progranulin-deficiency-on-amyloid-and-tau-pathologies-via-microglial-tyrobp-network
#20
Hideyuki Takahashi, Zoe A Klein, Sarah M Bhagat, Adam C Kaufman, Mikhail A Kostylev, Tsuneya Ikezu, Stephen M Strittmatter
Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies...
January 9, 2017: Acta Neuropathologica
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