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Mouse modell for alzheimers disease

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https://www.readbyqxmd.com/read/28241067/cyclin-y-mediated-transcript-profiling-reveals-several-important-functional-pathways-regulated-by-cyclin-y-in-hippocampal-neurons
#1
I-Seul Joe, Jong-Hwan Kim, Hanna Kim, Jung-Hwa Hong, Mirang Kim, Mikyoung Park
Cyclin Y (CCNY), which is a cyclin protein known to play a role in cell division, is unexpectedly and thus interestingly expressed in non-proliferating neuronal cells. There have been only a few studies reporting the neuronal functions of CCNY in synapse remodeling and hippocampal long-term potentiation. Therefore, we here provide global and comprehensive information on the putative functions of CCNY in biological and functional pathways in neuronal systems. We adopted high-throughput RNA-sequencing technology for analyzing transcriptomes regulated by CCNY and utilized bioinformatics for identifying putative molecules, biological processes, and functional pathways that are possibly connected to CCNY functions in hippocampal neuronal cells of rats...
2017: PloS One
https://www.readbyqxmd.com/read/28238547/hallmarks-of-alzheimer-s-disease-in-stem-cell-derived-human-neurons-transplanted-into-mouse-brain
#2
Ira Espuny-Camacho, Amaia M Arranz, Mark Fiers, An Snellinx, Kunie Ando, Sebastian Munck, Jerome Bonnefont, Laurie Lambot, Nikky Corthout, Lorna Omodho, Elke Vanden Eynden, Enrico Radaelli, Ina Tesseur, Selina Wray, Andreas Ebneth, John Hardy, Karelle Leroy, Jean-Pierre Brion, Pierre Vanderhaeghen, Bart De Strooper
Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration...
February 15, 2017: Neuron
https://www.readbyqxmd.com/read/28237843/characterization-of-energy-and-neurotransmitter-metabolism-in-cortical-glutamatergic-neurons-derived-from-human-induced-pluripotent-stem-cells-a-novel-approach-to-study-metabolism-in-human-neurons
#3
Blanca I Aldana, Yu Zhang, Maria Fog Lihme, Lasse K Bak, Jørgen E Nielsen, Bjørn Holst, Poul Hyttel, Kristine K Freude, Helle S Waagepetersen
Alterations in the cellular metabolic machinery of the brain are associated with neurodegenerative disorders such as Alzheimer's disease. Novel human cellular disease models are essential in order to study underlying disease mechanisms. In the present study, we characterized major metabolic pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U-(13)C]glucose, [U-(13)C]glutamate or [U-(13)C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass spectrometry, and cellular amino acid content was quantified by high-performance liquid chromatography...
February 22, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28237313/peripheral-administration-of-the-soluble-tnf-inhibitor-xpro1595-modifies-brain-immune-cell-profiles-decreases-beta-amyloid-plaque-load-and-rescues-impaired-long-term-potentiation-in-5xfad-mice
#4
Kathryn P MacPherson, Pradoldej Sompol, George T Kannarkat, Jianjun Chang, Lindsey Sniffen, Mary E Wildner, Christopher M Norris, Malú G Tansey
: Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer's disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen...
February 22, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28230352/disease-modifying-effects-of-m1-muscarinic-acetylcholine-receptor-activation-in-an-alzheimer-s-disease-mouse-model
#5
Evan P Lebois, Jason P Schroeder, Thomas J Esparza, Thomas M Bridges, Craig W Lindsley, P Jeffrey Conn, David L Brody, John Scott Daniels, Allan I Levey
Alzheimer's Disease (AD) is the leading cause of dementia worldwide and currently no disease-modifying therapy is available to slow or prevent AD, underscoring the urgent need for neuroprotective therapies. Selective M1 muscarinic acetylcholine receptor (mAChR) activation is an attractive mechanism for AD therapy since M1 mediates key effects on memory, cognition, and behavior and has potential for disease-modifying effects on Aβ formation and tau phosphorylation. To validate M1 as a neuroprotective treatment target for AD, the M1-selective agonist, VU0364572, was chronically dosed to 5XFAD mice from a young age preceding Aβ pathology (2 months) to an age where these mice are known to display memory impairments (6 months)...
February 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28223920/therapeutic-potential-of-secreted-amyloid-precursor-protein-apps%C3%AE
#6
REVIEW
Bruce G Mockett, Max Richter, Wickliffe C Abraham, Ulrike C Müller
Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great potential as a therapeutic target. For example, APPsα is neurotrophic, neuroprotective, neurogenic, a stimulator of protein synthesis and gene expression, and enhances long-term potentiation (LTP) and memory...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#7
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28222521/the-effects-of-lw-afc-on-the-hippocampus-transcriptome-in-senescence-accelerated-mouse-prone-8-strain-a-mouse-model-of-alzheimer-s-disease
#8
Jianhui Wang, Yang Liu, Xiaorui Cheng, Xiaorui Zhang, Feng Liu, Gang Liu, Shanyi Qiao, Ming Ni, Wenxia Zhou, Yongxiang Zhang, Fei Li
The senescence-accelerated mouse prone 8 (SAMP8) strain is considered a robust experimental model for developing preventative and therapeutic treatments for Alzheimer's disease (AD), a neurodegenerative disease which cannot be effectively prevented, halted, or cured. Our previous studies showed that LW-AFC, a new formula derived from the classical traditional Chinese medicinal prescription Liuwei Dihuang decoction, ameliorates cognitive deterioration in PrP-hAβPPswe/PS1ΔE9 transgenic mice and SAMP8 mice. This study aims to investigate the mechanism that mediates how LW-AFC improves cognitive deficit on the basis of the transcriptome...
February 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222512/aqp4-association-with-amyloid-deposition-and-astrocyte-pathology-in-the-tg-arcswe-mouse-model-of-alzheimer-s-disease
#9
Jing Yang, Rui Zhang, Changhe Shi, Chengyuan Mao, Zhihua Yang, Zhenhe Suo, Reidun Torp, Yuming Xu
Amyloid-β deposition in senile plaques is one of the main pathological changes in Alzheimer's disease (AD). We previously reported that aquaporin-4 (AQP4) is redistributed within the astrocytes in cerebral amyloid angiopathy in the tg-ArcSwe mouse model of AD, suggesting that AQP4 may participate in amyloid-β deposition. However, the role of AQP4 in plaque formation is not currently clear. The objective of the current study was to explore the AQP4 distribution within plaques in the tg-ArcSwe mice in more depth by the combined application of immunofluorescence cytochemistry and immunogold electron microscopy...
February 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222511/evaluation-of-a-dna-a%C3%AE-42-vaccine-in-aged-nzw-rabbits-antibody-kinetics-and-immune-profile-after-intradermal-immunization-with-full-length-dna-a%C3%AE-42-trimer
#10
Doris Lambracht-Washington, Min Fu, Mary Wight-Carter, Matthew Riegel, Roger N Rosenberg
A pathological hallmark of Alzheimer's disease (AD) are amyloid plaques in the brain consisting of aggregated amyloid-β 42 peptide (Aβ42) derived from cellular amyloid-β protein precursor (AβPP). Based on successful experiments in mouse AD models, active immunization with Aβ42 peptide and passive immunizations with anti-Aβ42 antibodies were started in clinical trials. Active Aβ42 peptide immunization in humans had led to an inflammatory autoimmune response, and the trial was stopped. Passive immunizations had shown some effects in slowing AD pathology...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222506/synaptic-compensation-as-a-probable-cause-of-prolonged-mild-cognitive-impairment-in-alzheimer-s-disease-implications-from-a-transgenic-mouse-model-of-the-disease
#11
Narjes Baazaoui, Michael Flory, Khalid Iqbal
Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease in which cognitive decline takes place over a period of several years with a very variable period of mild cognitive impairment (MCI) and, in some cases, relatively long period before progression to dementia. The cognitive deficit during MCI is probably due to neuronal loss, an intermediate level of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT) and synaptosis, which is interrupted with a transient compensatory increase. We found impairment in reference memory accompanied by a decrease in the expression of synaptophysin, β-III tubulin, and MAP2 and a trend for GluR1, at 12 weeks of age in 3xTg-AD mice (hAPPSwe, P301L tau, PS1 [M146V] knock-in), a widely used transgenic model of AD...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28218311/s-38093-a-histamine-h3-antagonist-inverse-agonist-promotes-hippocampal-neurogenesis-and-improves-context-discrimination-task-in-aged-mice
#12
Jean-Philippe Guilloux, Benjamin A Samuels, Indira Mendez-David, Alice Hu, Marjorie Levinstein, Charlène Faye, Maryam Mekiri, Elisabeth Mocaer, Alain M Gardier, René Hen, Aurore Sors, Denis J David
Strategies designed to increase adult hippocampal neurogenesis (AHN) may have therapeutic potential for reversing memory impairments. H3 receptor antagonists/inverse agonists also may be useful for treating cognitive deficits. However, it remains unclear whether these ligands have effects on AHN. The present study aimed to investigate the effects of a 28-day treatment with S 38093, a novel brain-penetrant antagonist/inverse agonist of H3 receptors, on AHN (proliferation, maturation and survival) in 3-month-old and in aged 16-month-old mice...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203484/lw-afc-effects-on-n-glycan-profile-in-senescence-accelerated-mouse-prone-8-strain-a-mouse-model-of-alzheimer-s-disease
#13
Jianhui Wang, Xiaorui Cheng, Ju Zeng, Jiangbei Yuan, Zhongfu Wang, Wenxia Zhou, Yongxiang Zhang
Glycosylation is one of the most common eukaryotic post-translational modifications, and aberrant glycosylation has been linked to many diseases. However, glycosylation and glycome analysis is a significantly challenging task. Although several lines of evidence have indicated that protein glycosylation is defective in Alzheimer's disease (AD), only a few studies have focused on AD glycomics. The etiology of AD is unclear and there are no effective disease-modifying treatments for AD. In this study, we found that the object recognition memory, passive avoidance, and spatial learning and memory of senescence-accelerated mouse prone 8 (SAMP8) strain, an AD animal model, were deficient, and LW-AFC, which was prepared from the traditional Chinese medicine prescription Liuwei Dihuang decoction, showed beneficial effects on the deterioration of cognitive capability in SAMP8 mice...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28193696/astrocytic-orosomucoid-2-modulates-microglial-activation-and-neuroinflammation
#14
Myungjin Jo, Jong-Heon Kim, Gyunjee Song, Minchul Seo, Eun Mi Hwang, Kyoungho Suk
Orosomucoid (ORM) is an acute-phase protein that belongs to the immunocalin subfamily, a group of small-molecule binding proteins with immunomodulatory functions. Little is known about the role of ORM proteins in the central nervous system. The aim of the present study was to investigate the brain expression of ORM and its role in neuroinflammation. Expression of Orm2, but not Orm1 or Orm3, was highly induced in the mouse brain after systemic injection of lipopolysaccharide (LPS). Plasma levels of ORM2 were also significantly higher in patients with cognitive impairment than in normal subjects...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28193453/energy-and-the-alzheimer-brain
#15
REVIEW
Mortimer Mamelak
The high energy demands of the poorly myelinated long axon hippocampal and cortical neurons render these neurons selectively vulnerable to degeneration in Alzheimer's disease. However, pathology engages all of the major elements of the neurovascular unit of the mature Alzheimer brain, the neurons, glia and blood vessels. Neurons present with retrograde degeneration of the axodendritic tree, capillaries with string vessels and markedly reduced densities and glia with signs of inflammatory activation. The neurons, capillaries and astrocytes of the mature Alzheimer brain harbor structurally defective mitochondria...
February 11, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28191738/the-role-of-neuroinflammation-and-amyloid-in-cognitive-impairment-in-an-app-ps1-transgenic-mouse-model-of-alzheimer-s-disease
#16
Shenghua Zhu, Junhui Wang, Yanbo Zhang, Jue He, Jiming Kong, Jun-Feng Wang, Xin-Min Li
AIMS: Both amyloid deposition and neuroinflammation appear in the early course of Alzheimer's disease (AD). However, the progression of neuroinflammation and its relationship with amyloid deposition and behavioral changes have not been fully elucidated. A better understanding the role of neuroinflammation in AD might extend our current knowledge to therapeutic intervention possibilities. METHODS: This study systematically characterized changes in behavioral abnormalities in APP/PS1 transgenic mice...
February 12, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28188358/protective-effect-of-valproic-acid-in-streptozotocin-induced-sporadic-alzheimer-s-disease-mouse-model-possible-involvement-of-the-cholinergic-system
#17
Mirna Ezzat Sorial, Nesrine Salah El Dine El Sayed
Sporadic Alzheimer's disease (SAD) is a slowly progressive neurological disorder that is the most common form of dementia. Cholinergic system dysfunction and amyloid beta formation are the two main underlying pathological mechanisms for the disease development. In recent studies, insulin receptor desensitization and disturbances in the downstream effects of insulin receptor signaling were observed in the brains of Alzheimer's patients. Currently, intracereberoventricular (ICV) injection of streptozotocin (STZ) is found to induce behavioral, neurochemical, and structural alterations in animals resembling those found in SAD patients...
February 10, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28176819/reduction-of-abeta-amyloid-pathology-in-appps1-transgenic-mice-in-the-absence-of-gut-microbiota
#18
T Harach, N Marungruang, N Duthilleul, V Cheatham, K D Mc Coy, G Frisoni, J J Neher, F Fåk, M Jucker, T Lasser, T Bolmont
Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176624/vitamin-d-combined-with-resveratrol-prevents-cognitive-decline-in-samp8-mice
#19
Jinbo Cheng, Yehua Rui, Liqiang Qin, Jiaying Xu, Shufen Han, Linxi Yuan, Xuebin Yin, Zhongxiao Wan
Background Vitamin D (VD) and resveratrol (RSV) are two nutritional molecules that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. The senescence-accelerated mouse-prone 8 (SAMP8) is a useful model of Alzheimer's disease (AD)-related memory impairment. Objective We aimed to explore how the combination of vitamin D with resveratrol would affect memory impairments shown by SAMP8 mice, as well as the potential mechanisms...
February 6, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28174113/involvement-of-glun2b-subunit-containing-n-methyl-d-aspartate-nmda-receptors-in-mediating-the-acute-and-chronic-synaptotoxic-effects-of-oligomeric-amyloid-beta-a%C3%AE-in-murine-models-of-alzheimer-s-disease-ad
#20
Gerhard Rammes, Corinna Mattusch, Matthias Wulff, Franziska Seeser, Matthias Kreuzer, Kaichuan Zhu, Jan M Deussing, Jochen Herms, Chris G Parsons
To elucidate whether a permanent reduction of the GluN2B subunit affects the pathology of Alzheimer's disease (AD), we cross-bred mice heterozygous for GluN2B receptors in the forebrain (hetGluN2B) with a mouse model for AD carrying a mutated amyloid precursor protein with the Swedish and Arctic mutation (mAPP) resulting in a hetGluN2B/mAPP transgenic. By means of voltage-sensitive dye imaging (VSDI) in the di-synaptic hippocampal pathway and the recording of field excitatory postsynaptic potentials (fEPSPs), hippocampal slices of all genotypes (WT, hetGluN2B, mAPP and hetGluN2B/mAPP, age 9-18 months) were tested for spatiotemporal activity propagation and LTP induction...
February 4, 2017: Neuropharmacology
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