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https://www.readbyqxmd.com/read/28641136/age-exacerbates-abnormal-protein-expression-in-a-mouse-model-of-down-syndrome
#1
Md Mahiuddin Ahmed, Aaron Block, Suhong Tong, Muriel T Davisson, Katheleen J Gardiner
The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non-human chromosome 21 orthologous proteins are greater at 12 months than at ∼6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer's disease...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28641125/an-altered-redox-environment-assisted-by-over-expression-of-fetal-hemoglobins-protects-from-inflammatory-colitis-and-reduces-inflammatory-cytokine-expression
#2
R M Gorczynski, C Alexander, K Brandenburg, Z Chen, A Heini, D Neumann, J P Mach, E T Rietschel, A Tersikh, A J Ulmer, Kai Yu, U Zahringer, I Khatri
C5BL/6 female mice receiving dextran sodium sulfate in their drinking water develop an acute inflammatory colitis within 7d, with weight loss, histopathologic signs of inflammation, and colonic expression of inflammatory cytokines. In previous studies we have reported that increased inflammatory cytokine expression in aged mice can be attenuated by oral gavage of a crude fetal extract containing glutathione (GSH), MPLA and fetal hemoglobin, or more specifically by injection of a combination of these purified reagents...
June 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28640904/correlation-of-disease-severity-with-body-weight-and-high-fat-diet-in-the-fatzo-pco-mouse
#3
Brian A Droz, Bria L Sneed, Charles V Jackson, Karen M Zimmerman, M Dodson Michael, Paul J Emmerson, Tamer Coskun, Richard G Peterson
Obesity in many current pre-clinical animal models of obesity and diabetes is mediated by monogenic mutations; these are rarely associated with the development of human obesity. A new mouse model, the FATZO mouse, has been developed to provide polygenic obesity and a metabolic pattern of hyperglycemia and hyperinsulinemia, that support the presence of insulin resistance similar to metabolic disease in patients with insulin resistance/type 2 diabetes. The FATZO mouse resulted from a cross of C57BL/6J and AKR/J mice followed by selective inbreeding for obesity, increased insulin and hyperglycemia...
2017: PloS One
https://www.readbyqxmd.com/read/28640861/inhibition-of-nf-%C3%AE%C2%BAb-improves-the-stress-resistance-and-myogenic-differentiation-of-mdspcs-isolated-from-naturally-aged-mice
#4
Jonathan D Proto, Aiping Lu, Akaitz Dorronsoro, Alex Scibetta, Paul D Robbins, Laura J Niedernhofer, Johnny Huard
A decline in the regenerative capacity of adult stem cells with aging is well documented. As a result of this decline, the efficacy of autologous stem cell therapies is likely to decline with increasing donor age. In these cases, strategies to restore the function of aged stem cells would have clinical utility. Globally, the transcription factor NF-κB is up-regulated in aged tissues. Given the negative role that NF-κB plays in myogenesis, we investigated whether the age-related decline in the function of muscle-derived stem/progenitor cells (MDSPCs) could be improved by inhibition of NF-κB...
2017: PloS One
https://www.readbyqxmd.com/read/28640857/glucose-dysregulation-and-response-to-common-anti-diabetic-agents-in-the-fatzo-pco-mouse
#5
Richard G Peterson, Charles Van Jackson, Karen M Zimmerman, Jorge Alsina-Fernandez, M Dodson Michael, Paul J Emmerson, Tamer Coskun
The FATZO/Pco mouse is the result of a cross of the C57BL/6J and AKR/J strains. The crossing of these two strains and the selective inbreeding for obesity, insulin resistance and hyperglycemia has resulted in an inbred strain exhibiting obesity in the presumed presence of an intact leptin pathway. Routinely used rodent models for obesity and diabetes research have a monogenic defect in leptin signaling that initiates obesity. Given that obesity and its sequelae in humans are polygenic in nature and not associated with leptin signaling defects, the FATZO mouse may represent a more translatable rodent model for study of obesity and its associated metabolic disturbances...
2017: PloS One
https://www.readbyqxmd.com/read/28637206/improving-combination-osteoporosis-therapy-in-a-preclinical-model-of-heightened-osteoanabolism
#6
Yu Shao, Selene Hernandez-Buquer, Paul Childress, Keith R Stayrook, Marta B Alvarez, Hannah Davis, Lilian Plotkin, Yongzheng He, Keith W Condon, David B Burr, Stuart J Warden, Alexander G Robling, Feng-Chun Yang, Ronald C Wek, Matthew R Allen, Joseph P Bidwell
Combining anti-catabolic agents with parathyroid hormone (PTH) to enhance bone mass has yielded mixed results in osteoporosis patients. Towards the goal of enhancing the efficacy of these regimens, we tested their utility in combination with loss of the transcription factor Nmp4 since disabling this gene amplifies PTH-induced increases in trabecular bone in mice by boosting osteoblast secretory activity. We addressed whether combining a sustained anabolic response with an anti-catabolic results in superior bone acquisition compared to PTH mono-therapy...
June 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28636406/protective-effect-of-intravitreal-administration-of-exosomes-derived-from-mesenchymal-stem-cells-on-retinal-ischemia
#7
Elad Moisseiev, Johnathon D Anderson, Sharon Oltjen, Mayank Goswami, Robert J Zawadzki, Jan A Nolta, Susanna S Park
PURPOSE: Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model. METHODS: Oxygen-induced retinopathy (OIR) was induced by exposing one-week-old male C57BL/6J mice to 5 days of 75% hyperoxic conditioning, and returning to room air. After hyperoxic conditioning, the right eye of each mouse was injected intravitreally with 1 µl saline or exosomes derived from hMSCs and compared to control mice of the same age raised in room air without OIR injected intravitreally with saline...
June 21, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#8
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28635176/genetic-loss-of-the-muscarinic-m3-receptor-m3-r-markedly-alters-bile-formation-and-cholestatic-liver-injury-in-mice
#9
Franziska Durchschein, Elisabeth Krones, Marion J Pollheimer, Gernot Zollner, Martin Wagner, Jean-Pierre Raufman, Peter Fickert
Hepatic innervation represents a potentially underestimated regulator of liver function and regeneration. The muscarinic 3 receptor (M3 -R) is the primary cholangiocyte receptor for the afferent parasympathetic innervation of bile ducts. We aimed to determine the specific role of the M3 -R in bile formation and models for cholestatic liver disease in mice. We compared bile flow and composition in M3 -R knock-out mice (M3 -R(-/-) ) and wild type littermates (WT). M3 -R(-/-) mice showed significantly reduced bile flow compared to WT mice, most likely due to decreased biliary HCO3(-) secretion...
June 21, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28634890/ccl11-eotaxin-1-levels-predict-long-term-functional-outcomes-in-patients-following-ischemic-stroke
#10
Meaghan Roy-O'Reilly, Rodney M Ritzel, Sarah E Conway, Ilene Staff, Gilbert Fortunato, Louise D McCullough
Circulating levels of the pro-inflammatory cytokine C-C motif chemokine 11 (CCL11, also known as eotaxin-1) are increased in several animal models of neuroinflammation, including traumatic brain injury and Alzheimer's disease. Increased levels of CCL11 have also been linked to decreased neurogenesis in mice. We hypothesized that circulating CCL11 levels would increase following ischemic stroke in mice and humans, and that higher CCL11 levels would correlate with poor long-term recovery in patients. As predicted, circulating levels of CCL11 in both young and aged mice increased significantly 24 h after experimental stroke...
June 21, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28634450/leonurine-improves-age-dependent-impaired-angiogenesis-possible-involvement-of-mitochondrial-function-and-hif-1%C3%AE-dependent-vegf-activation
#11
Jia Qi, Jing J Wang, Jun L Duan, Zhao Y Lu, Yang G Yuan
Objective: Advanced age is associated with impaired angiogenesis in part because of mitochondrial dysfunction. We have recently reported that leonurine exerts protective effects in neuron via regulation of mitochondrial function. The aim of this study was to explore whether leonurine is able to attenuate mitochondrial dysfunction and to enhance angiogenesis in old rats with hindlimb ischemia. Methods and Results: At day 14 after surgery, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression was decreased in the ischemic muscle of aged animals, which was accompanied by enhanced oxidative stress, increased mitochondrial damage, decreased capillary density, and reduced limb perfusion compared with young mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28634345/sirtuin-3-deficiency-does-not-alter-host-defenses-against-bacterial-and-fungal-infections
#12
Eleonora Ciarlo, Tytti Heinonen, Jérôme Lugrin, Hans Acha-Orbea, Didier Le Roy, Johan Auwerx, Thierry Roger
Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase. SIRT3 regulates cell metabolism and redox homeostasis, and protects from aging and age-associated pathologies. SIRT3 may drive both oncogenic and tumor-suppressive effects. SIRT3 deficiency has been reported to promote chronic inflammation-related disorders, but whether SIRT3 impacts on innate immune responses and host defenses against infections remains essentially unknown. This aspect is of primary importance considering the great interest in developing SIRT3-targeted therapies...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633487/high-intensity-interval-training-hiit-improves-physical-performance-and-frailty-in-aged-mice
#13
Kenneth Ladd Seldeen, Ginger Lasky, Merced Maria Leiker, Manhui Pang, Kirkwood Ely Personius, Bruce Robert Troen
Sarcopenia and frailty are highly prevalent in older individuals, increasing the risk of disability and loss of independence. High intensity interval training (HIIT) may provide a robust intervention for both sarcopenia and frailty by achieving both strength and endurance benefits with lower time commitments than other exercise regimens. To better understand the impacts of HIIT during aging, we compared 24-month-old C57BL/6J sedentary mice with those that were administered 10-minute uphill treadmill HIIT sessions three times per week over 16 weeks...
June 17, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28632647/high-osteogenic-potential-of-adipose-and-muscle-derived-mesenchymal-stem-cells-in-spinal-ossification-model-mice
#14
Xizhe Liu, Gentaro Kumagai, Kanichiro Wada, Toshihiro Tanaka, Toru Asari, Kazuki Oishi, Taku Fujita, Hiroki Mizukami, Ken-Ichi Furukawa, Yasuyuki Ishibashi
STUDY DESIGN: Basic experiments in a mouse model of ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To assess the osteogenic potential of mesenchymal stem cells (MSCs) obtained from muscle and adipose tissue in Tiptoe-walking (ttw) mice, in which cervical OPLL compresses the spinal cord and causes motor and sensory dysfunction. SUMMARY OF BACKGROUND DATA: In humans, MSCs have been implicated in the pathogenesis of cervical OPLL...
June 19, 2017: Spine
https://www.readbyqxmd.com/read/28632458/aquaporins-novel-targets-for-age-related-ocular-disorders
#15
Rajkumar Patil, Haishan Wang, Najam A Sharif, Alok Mitra
Aquaporins (AQPs), a large family of membrane protein channels that facilitate transport of water and other small solutes, play important roles in physiological functions and human diseases. Up till now, 13 types of AQPs, numbered 0 through 12, have been identified in various mammalian tissues. Homologous genes for AQPs in amphibians, insects, and bacteria highlight the evolutionary conservation and, thus, the importance of these membrane channels. Many members of the AQP family are expressed in the eye. AQP1, which is a water-selective channel, is expressed in the anterior chamber (cornea, ciliary body, trabecular meshwork) and posterior chamber (retina and microvessels in choroid), controlling the fluid homeostasis in the eye...
June 20, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28632204/successful-pharmacotherapy-for-the-treatment-of-severe-feeding-aversion-with-mechanistic-insights-from-cross-species-neuronal-remodeling
#16
W G Sharp, A G Allen, K H Stubbs, K K Criado, R Sanders, C E McCracken, R G Parsons, L Scahill, S L Gourley
Pediatric feeding disorders affect up to 5% of children, causing severe food intake problems that can result in serious medical and developmental outcomes. Behavioral intervention (BI) is effective in extinguishing feeding aversions, and also expert-dependent, time/labor-intensive and not well understood at a neurobiological level. Here we first conducted a double-blind, placebo-controlled trial comparing BI with BI plus d-cycloserine (DCS). DCS is a partial N-methyl-d-aspartate (NMDA) receptor agonist shown to augment extinction therapies in multiple anxiety disorders...
June 20, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28632181/spirulina-protects-against-hepatic-inflammation-in-aging-an-effect-related-to-the-modulation-of-the-gut-microbiota
#17
Audrey M Neyrinck, Bernard Taminiau, Hannah Walgrave, Georges Daube, Patrice D Cani, Laure B Bindels, Nathalie M Delzenne
Aging predisposes to hepatic dysfunction and inflammation that can contribute to the development of non-alcoholic fatty liver disease. Spirulina, a cyanobacterium used as a food additive or food supplement, has been shown to impact immune function. We have tested the potential hepatoprotective effect of a Spirulina in aged mice and to determine whether these effects can be related to a modulation of the gut microbiota. Old mice have been fed a standard diet supplemented with or without 5% Spirulina for six weeks...
June 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28631843/age-related-spontaneous-lumbar-intervertebral-disc-degeneration-in-a-mouse-model
#18
Takashi Ohnishi, Hideki Sudo, Takeru Tsujimoto, Norimasa Iwasaki
The pathogenesis of intervertebral disc degeneration is unclear, but it is a major cause of several spinal diseases. Animal models have historically provided an appropriate benchmark for understanding the human spine. However, there is little information about when intervertebral disc degeneration begins in the mouse or regarding the relationship between magnetic resonance imaging and histological findings. The aim for this study was to obtain information about age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine using magnetic resonance imaging and a histological score regarding when the intervertebral disc degeneration started and how rapidly it progressed, as well as how our histological score detected the degeneration...
June 20, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28631813/high-fat-diet-attenuates-hyperglycemia-body-composition-changes-and-bone-loss-in-male-streptozotocin-induced-type-1-diabetic-mice
#19
Adriana Lelis Carvalho, Victoria E DeMambro, Anyonya R Guntur, Phuong Le, Kenichi Nagano, Roland Baron, Francisco José Albuquerque de Paula, Katherine J Motyl
There is a growing and alarming prevalence of obesity and the metabolic syndrome in type I diabetic patients (T1DM), particularly in adolescence. In general, low bone mass, higher fracture risk and increased marrow adipose tissue (MAT) are features of diabetic osteopathy in insulin deficient subjects. On the other hand, type 2 diabetes (T2DM) is associated with normal or high bone mass, a greater risk of peripheral fractures and no change in MAT. Therefore, we sought to determine the effect of weight gain on bone turnover in insulin deficient mice...
June 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28631230/sequence-analysis-of-chromosome-1-revealed-different-selection-patterns-between-chinese-wild-mice-and-laboratory-strains
#20
Fuyi Xu, Shixian Hu, Tianzhu Chao, Maochun Wang, Kai Li, Yuxun Zhou, Hongyan Xu, Junhua Xiao
Both natural and artificial selection play a critical role in animals' adaptation to the environment. Detection of the signature of selection in genomic regions can provide insights for understanding the function of specific phenotypes. It is generally assumed that laboratory mice may experience intense artificial selection while wild mice more natural selection. However, the differences of selection signature in the mouse genome and underlying genes between wild and laboratory mice remain unclear. In this study, we used two mouse populations: chromosome 1 (Chr 1) substitution lines (C1SLs) derived from Chinese wild mice and mouse genome project (MGP) sequenced inbred strains and two selection detection statistics: Fst and Tajima's D to identify the signature of selection footprint on Chr 1...
June 19, 2017: Molecular Genetics and Genomics: MGG
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