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Mouse modell for alzheimers disease

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https://www.readbyqxmd.com/read/28527208/neuronal-expression-of-truncated-tau-efficiently-promotes-neurodegeneration-in-animal-models-pitfalls-of-toxic-oligomer-analysis
#1
Rostislav Skrabana, Branislav Kovacech, Peter Filipcik, Norbert Zilka, Santosh Jadhav, Tomas Smolek, Eva Kontsekova, Michal Novak
Animal models of neurodegeneration induced by neuronal expression of truncated tau protein emerge as an important tool for understanding the pathogenesis of human tauopathies and for therapy development. Here we highlight common features of truncated tau models and make a critical assessment of possible pitfalls in their analysis. Particularly, the amount of soluble tau oligomers, which are suspected to be neurotoxic agents participating on the spreading of pathology inside the brain, may be overestimated due to a post-lysis oxidative tau oligomerization...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28523553/dna-modifications-and-alzheimer-s-disease
#2
Rebecca G Smith, Katie Lunnon
Alzheimer's disease (AD) is a complex neurodegenerative disease, affecting millions of people worldwide. While a number of studies have focused on identifying genetic variants that contribute to the development and progression of late-onset AD, the majority of these only have a relatively small effect size. There are also a number of other risk factors, for example, age, gender, and other comorbidities; however, how these influence disease risk is not known. Therefore, in recent years, research has begun to investigate epigenetic mechanisms for a potential role in disease etiology...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28522250/ppargamma-agonists-rescue-increased-phosphorylation-of-fgf14-at-s226-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#3
Wei-Chun J Hsu, Norelle Wildburger, Sigmund J Haidacher, Miroslav N Nenov, Oluwarotimi Folorunso, Aditya K Singh, Brent C Chesson, Whitney F Franklin, Ibdanelo Cortez, Rovshan G Sadygov, Kelly T Dineley, Jai Rudra, Giulio Taglialatela, Cheryl F Lichti, Larry Denner, Fernanda Laezza
BACKGROUND: Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal model of AD, RSG treatment rescued cognitive deficits and reduced aberrant activity of granule neurons in the dentate gyrus (DG), an area critical for memory formation...
May 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28521765/inhibition-of-o-glcnacase-leads-to-elevation-of-o-glcnac-tau-and-reduction-of-tauopathy-and-cerebrospinal-fluid-tau-in-rtg4510-mice
#4
Nicholas B Hastings, Xiaohai Wang, Lixin Song, Brent D Butts, Diane Grotz, Richard Hargreaves, J Fred Hess, Kwok-Lam Karen Hong, Cathy Ruey-Ruey Huang, Lynn Hyde, Maureen Laverty, Julie Lee, Diane Levitan, Sherry X Lu, Maureen Maguire, Veeravan Mahadomrongkul, Ernest J McEachern, Xuesong Ouyang, Thomas W Rosahl, Harold Selnick, Michaela Stanton, Giuseppe Terracina, David J Vocadlo, Ganfeng Wang, Joseph L Duffy, Eric M Parker, Lili Zhang
BACKGROUND: Hyperphosphorylation of microtubule-associated protein tau is a distinct feature of neurofibrillary tangles (NFTs) that are the hallmark of neurodegenerative tauopathies. O-GlcNAcylation is a lesser known post-translational modification of tau that involves the addition of N-acetylglucosamine onto serine and threonine residues. Inhibition of O-GlcNAcase (OGA), the enzyme responsible for the removal of O-GlcNAc modification, has been shown to reduce tau pathology in several transgenic models...
May 18, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28520620/-epigallocatechin-3-gallate-ameliorates-memory-impairment-and-rescues-the-abnormal-synaptic-protein-levels-in-the-frontal-cortex-and-hippocampus-in-a-mouse-model-of-alzheimer-s-disease
#5
Yufang Guo, Yan Zhao, Ying Nan, Xiang Wang, Yulong Chen, Shuang Wang
(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic extract in green tea and it has attracted increasing attention for its multiple bioactive effects. However, the mechanisms by which EGCG exerts its neuroprotective actions in Alzheimer's disease (AD) are presently lacking. In the present study, a sporadic AD transgenic mouse model known as senescence-accelerated mouse prone 8 (SAMP8) was used to investigate whether oral administration of EGCG could improve recognition and memory function through reduction of amyloid β (Aβ) and tau hyperphosphorylation...
May 17, 2017: Neuroreport
https://www.readbyqxmd.com/read/28518113/enhanced-sample-multiplexing-of-tissues-using-combined-precursor-isotopic-labeling-and-isobaric-tagging-cpilot
#6
Christina D King, Joseph D Dudenhoeffer, Liqing Gu, Adam R Evans, Renã A S Robinson
There is an increasing demand to analyze many biological samples for disease understanding and biomarker discovery. Quantitative proteomics strategies that allow simultaneous measurement of multiple samples have become widespread and greatly reduce experimental costs and times. Our laboratory developed a technique called combined precursor isotopic labeling and isobaric tagging (cPILOT), which enhances sample multiplexing of traditional isotopic labeling or isobaric tagging approaches. Global cPILOT can be applied to samples originating from cells, tissues, bodily fluids, or whole organisms and gives information on relative protein abundances across different sample conditions...
May 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28518111/using-enzyme-based-biosensors-to-measure-tonic-and-phasic-glutamate-in-alzheimer-s-mouse-models
#7
Holly C Hunsberger, Sharay E Setti, Ryan T Heslin, Jorge E Quintero, Greg A Gerhardt, Miranda N Reed
Neurotransmitter disruption is often a key component of diseases of the central nervous system (CNS), playing a role in the pathology underlying Alzheimer's disease, Parkinson's disease, depression, and anxiety. Traditionally, microdialysis has been the most common (lauded) technique to examine neurotransmitter changes that occur in these disorders. But because microdialysis has the ability to measure slow 1-20 minute changes across large areas of tissue, it has the disadvantage of invasiveness, potentially destroying intrinsic connections within the brain and a slow sampling capability...
May 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28516241/innate-immunity-in-alzheimer-s-disease-the-relevance-of-animal-models
#8
REVIEW
Diana K Franco Bocanegra, James A R Nicoll, Delphine Boche
The mouse is one of the organisms most widely used as an animal model in biomedical research, due to the particular ease with which it can be handled and reproduced in laboratory. As a member of the mammalian class, mice share with humans many features regarding metabolic pathways, cell morphology and anatomy. However, important biological differences between mice and humans exist and must be taken into consideration when interpreting research results, to properly translate evidence from experimental studies into information that can be useful for human disease prevention and/or treatment...
May 17, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28514851/blood-brain-barrier-penetrating-biologic-tnf-%C3%AE-inhibitor-for-alzheimer-s-disease
#9
Rudy Chang, Jillian Knox, Jae Chang, Aram Derbedrossian, Vitaly Vasilevko, David Cribbs, Ruben J Boado, William M Pardridge, Rachita Sumbria
OBJECTIVE: Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28512130/combination-therapy-with-octyl-gallate-and-ferulic-acid-improves-cognition-and-neurodegeneration-in-a-transgenic-mouse-model-of-alzheimer-disease
#10
Takashi Mori, Naoki Koyama, Jun Tan, Tatsuya Segawa, Masahiro Maeda, Terrence Town
To date, there is no effective Alzheimer disease (AD) modifying therapy. Nonetheless, combination therapy holds promise, and nutraceuticals (natural dietary compounds with therapeutic properties) and their synthetic derivatives are well-tolerated candidates. We tested whether combination therapy with octyl gallate (OG) and ferulic acid (FA) improves cognition and mitigates AD-like pathology in the PSAPP transgenic mouse model of cerebral amyloidosis. One-year-old mice with established β-amyloid plaques received daily doses of OG and FA alone or in combination for 3 months...
May 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28511979/water-and-t-maze-protocols-are-equally-efficient-methods-to-assess-spatial-memory-in-3xtg-alzheimer-s-disease-mice
#11
K E Davis, K Burnett, J Gigg
Rodent spatial memory is commonly tested using the water-maze; however, there is a potential confound of stress on learning in this behavioural paradigm. This is particularly relevant when testing spatial memory in models of neurodegeneration, such as the 3xTg mouse model for Alzheimer's disease. Here, we first confirmed that 3xTgAD mice express fear conditioning and then compared the performance of young and middle-aged mice on short-duration versions of the radial arm water-maze (RAWM) and the minimally stressful T-maze spontaneous alternation task...
May 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28511572/mtor-drives-cerebral-blood-flow-and-memory-deficits-in-ldlr-mice-modeling-atherosclerosis-and-vascular-cognitive-impairment
#12
Jordan B Jahrling, Ai-Ling Lin, Nicholas DeRosa, Stacy A Hussong, Candice E Van Skike, Milena Girotti, Martin Javors, Qingwei Zhao, Leigh Ann Maslin, Reto Asmis, Veronica Galvan
We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28506438/prion-like-spreading-in-tauopathies
#13
REVIEW
Jacob I Ayers, Benoit I Giasson, David R Borchelt
Tau is a microtubule-associated protein that functions in regulating cytoskeleton dynamics, especially in neurons. Misfolded and aggregated forms of tau produce pathological structures in a number of neurodegenerative diseases, including Alzheimer's disease (AD) and tauopathy dementias. These disorders can present with a sporadic etiology, such as in AD, or a familial etiology, such as in some cases of frontotemporal dementia with parkinsonism. Notably, the pathological features of tau pathology in these diseases can be very distinct...
April 13, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28505967/nfatc2-modulates-microglial-activation-in-the-a%C3%AE-pp-ps1-mouse-model-of-alzheimer-s-disease
#14
Gunjan D Manocha, Atreyi Ghatak, Kendra L Puig, Susan D Kraner, Christopher M Norris, Colin K Combs
Alzheimer's disease (AD) brains are characterized by fibrillar amyloid-β (Aβ) peptide containing plaques and associated reactive microglia. The proinflammatory phenotype of the microglia suggests that they may negatively affect disease course and contribute to behavioral decline. This hypothesis predicts that attenuating microglial activation may provide benefit against disease. Prior work from our laboratory and others has characterized a role for the transcription factor, nuclear factor of activated T cells (NFAT), in regulating microglial phenotype in response to different stimuli, including Aβ peptide...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28505105/new-functions-of-apc-c-ubiquitin-ligase-in-the-nervous-system-and-its-role-in-alzheimer-s-disease
#15
REVIEW
Tanja Fuchsberger, Ana Lloret, Jose Viña
The E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) regulates important processes in cells, such as the cell cycle, by targeting a set of substrates for degradation. In the last decade, APC/C has been related to several major functions in the nervous system, including axon guidance, synaptic plasticity, neurogenesis, and neuronal survival. Interestingly, some of the identified APC/C substrates have been related to neurodegenerative diseases. There is an accumulation of some degradation targets of APC/C in Alzheimer's disease (AD) brains, which suggests a dysregulation of the protein complex in the disorder...
May 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28504673/a-fluoro-nissl-dye-identifies-pericytes-as-distinct-vascular-mural-cells-during-in-vivo-brain-imaging
#16
Eyiyemisi C Damisah, Robert A Hill, Lei Tong, Katie N Murray, Jaime Grutzendler
Pericytes and smooth muscle cells are integral components of the brain microvasculature. However, no techniques exist to unambiguously identify these cell types, greatly limiting their investigation in vivo. Here we show that the fluorescent Nissl dye NeuroTrace 500/525 labels brain pericytes with specificity, allowing high-resolution optical imaging in the live mouse. We demonstrate that capillary pericytes are a population of mural cells with distinct morphological, molecular and functional features that do not overlap with precapillary or arteriolar smooth muscle actin-expressing cells...
May 15, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28502704/ketogenic-diet-leads-to-o-glcnac-modification-in-the-btbr-t-tf-j-mouse-model-of-autism
#17
Christopher Newell, Virginia L Johnsen, Nellie C Yee, Warren J Xu, Matthias S Klein, Aneal Khan, Jong M Rho, Jane Shearer
BACKGROUND: Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBR(T+tf/j) (BTBR) mouse model of ASD...
May 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28502066/ebselen-ameliorates-%C3%AE-amyloid-pathology-tau-pathology-and-cognitive-impairment-in-triple-transgenic-alzheimer-s-disease-mice
#18
Yongli Xie, Yibin Tan, Youbiao Zheng, Xiubo Du, Qiong Liu
Alzheimer's disease (AD) is a progressive neurodegenerative disease which is clinically characterized by memory loss and cognitive decline caused by protein misfolding and aggregation. Imbalance between free radicals and the antioxidant system is a prominent and early feature in the neuropathology of AD. Selenium (Se), a vital trace element with excellent antioxidant potential, is preferentially retained in the brain in Se-limited conditions and has been reported to provide neuroprotection through resisting oxidative damage...
May 13, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28501671/multifunctional-liposomes-delay-phenotype-progression-and-prevent-memory-impairment-in-a-presymptomatic-stage-mouse-model-of-alzheimer-disease
#19
Simona Mancini, Claudia Balducci, Edoardo Micotti, Daniele Tolomeo, Gianluigi Forloni, Massimo Masserini, Francesca Re
The failure of clinical trials largely focused on mild to moderate stages of Alzheimer disease has suggested to the scientific community that the effectiveness of Amyloid-β (Aβ)-centered treatments should be evaluated starting as early as possible, well before irreversible brain damage has occurred. Accordingly, also the preclinical development of new therapies should be carried out taking into account this suggestion. In the present investigation we evaluated the efficacy of a treatment with liposomes multifunctionalized for crossing the blood-brain barrier and targeting Aβ, carried out on young APP/PS1 Tg mice, taken as a model of pre-symptomatic disease stage...
May 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28500878/identification-of-changes-in-neuronal-function-as-a-consequence-of-aging-and-tauopathic-neurodegeneration-using-a-novel-and-sensitive-magnetic-resonance-imaging-approach
#20
Sarah N Fontaine, Alexandria Ingram, Ryan A Cloyd, Shelby E Meier, Emily Miller, Danielle Lyons, Grant K Nation, Elizabeth Mechas, Blaine Weiss, Chiara Lanzillotta, Fabio Di Domenico, Frederick Schmitt, David K Powell, Moriel Vandsburger, Jose F Abisambra
Tauopathies, the most common of which is Alzheimer's disease (AD), constitute the most crippling neurodegenerative threat to our aging population. Tauopathic patients have significant cognitive decline accompanied by irreversible and severe brain atrophy, and it is thought that neuronal dysfunction begins years before diagnosis. Our current understanding of tauopathies has yielded promising therapeutic interventions but have all failed in clinical trials. This is partly due to the inability to identify and intervene in an effective therapeutic window early in the disease process...
April 18, 2017: Neurobiology of Aging
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