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https://www.readbyqxmd.com/read/28918469/aversive-and-non-aversive-memory-impairment-in-the-mucopolysaccharidosis-ii-mouse-model
#1
Amanda Stapenhorst Azambuja, Lilian Correa, Bernardo Pappi Gabiatti, Giselle Renata Martins, Álvaro de Oliveira Franco, Maria Flávia Marques Ribeiro, Guilherme Baldo
Hunter syndrome (MPS II, OMIM 309900) is a lysosomal storage disorder due to deficient iduronate sulphatase activity. Patients present multiple cognitive alterations, and the aim of this work was to verify if MPS II mice also present some progressive cognitive alterations. For that, MPS II mice from 2 to 6 months of age were submitted to repeated open field and inhibitory avoidance tests to evaluate memory parameters. MPS II mice presented impaired memory at 6 months evaluated by open field test. They also performed poorly in the inhibitory avoidance test from 4 months...
September 16, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28918254/permissive-role-for-mglu1-metabotropic-glutamate-receptors-in-excitotoxic-retinal-degeneration
#2
Francesca Liberatore, Domenico Bucci, Giada Mascio, Michele Madonna, Paola Di Pietro, Martina Beneventano, Alda Maria Puliti, Giuseppe Battaglia, Valeria Bruno, Ferdinando Nicoletti, Maria Rosaria Romano
Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age- related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. Mice at postnatal day 9 were challenged with a toxic dose of monosodium glutamate (MSG, 3 g/kg), which caused the death of >70% of Brn-3a(+) RGCs...
September 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28918027/adeno-associated-viral-vector-mediated-mtor-inhibition-by-short-hairpin-rna-suppresses-laser-induced-choroidal-neovascularization
#3
Tae Kwann Park, Si Hyung Lee, Jun Sub Choi, Seung Kwan Nah, Hee Jong Kim, Ha Yan Park, Heuiran Lee, Steven Hyun Seung Lee, Keerang Park
Choroidal neovascularization (CNV) is the defining characteristic feature of the wet subtype of age-related macular degeneration (AMD) and may result in irreversible blindness. Based on anti-vascular endothelial growth factor (anti-VEGF), the current therapeutic approaches to CNV are fraught with difficulties, and mammalian target of rapamycin (mTOR) has recently been proposed as a possible therapeutic target, although few studies have been conducted. Here, we show that a recombinant adeno-associated virus-delivered mTOR-inhibiting short hairpin RNA (rAAV-mTOR shRNA), which blocks the activity of both mTOR complex 1 and 2, represents a promising therapeutic approach for the treatment of CNV...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917978/sen1500-a-novel-oral-amyloid-%C3%AE-aggregation-inhibitor-attenuates-brain-pathology-in-a-mouse-model-of-alzheimer-s-disease
#4
D Brunner, S Flunkert, J Neddens, S Duller, D I C Scopes, J M Treherne, B Hutter-Paier
INTRODUCTION: Amyloid-β (Aβ) aggregation is thought to be a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The development of new drugs inhibiting the Aβ aggregation process is, therefore, important. SEN1500, an orally bioavailable and CNS-penetrant Aβ aggregation inhibitor, has previously been shown to reduce spatial learning and memory deficits in an APP transgenic mouse model. To verify that the pharmacological properties of SEN1500 are not unique to this model, we investigated brain Aβ pathology, neuroinflammation, as well as memory in a different mouse model of AD expressing the human amyloid precursor protein with Swedish and London mutations (APPSL)...
September 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28917663/leucine-rich-%C3%AE-2-glycoprotein-overexpression-in-the-brain-contributes-to-memory-impairment
#5
Chihiro Akiba, Madoka Nakajima, Masakazu Miyajima, Ikuko Ogino, Masami Miura, Ritsuko Inoue, Eri Nakamura, Fumio Kanai, Norihiro Tada, Miyuki Kunichika, Mitsutaka Yoshida, Kinya Nishimura, Akihide Kondo, Hidenori Sugano, Hajime Arai
We previously reported increase in leucine-rich α2-glycoprotein (LRG) concentration in cerebrospinal fluid is associated with cognitive decline in humans. To investigate relationship between LRG expression in the brain and memory impairment, we analyzed transgenic mice overexpressing LRG in the brain (LRG-Tg) focusing on hippocampus. Immunostaining and Western blotting revealed age-related increase in LRG expression in hippocampal neurons in 8-, 24-, and 48-week-old controls and LRG-Tg. Y-maze and Morris water maze tests indicated retained spatial memory in 8- and 24-week-old LRG-Tg, while deteriorated in 48-week-old LRG-Tg compared with age-matched controls...
August 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28917185/ghrelin-and-hypothalamic-npy-agrp-expression-in-mice-are-affected-by-chronic-early-life-stress-exposure-in-a-sex-specific-manner
#6
K Y Yam, S R Ruigrok, I Ziko, S N De Luca, P J Lucassen, S J Spencer, A Korosi
Early-life stress (ES) is a risk factor for metabolic disorders (e.g. obesity) with a notoriously higher prevalence in women compared to men. However, mechanisms underlying these effects remain elusive. The development of the hypothalamic feeding and metabolic regulatory circuits occurs mostly in the early sensitive postnatal phase in rodents and is tightly regulated by the metabolic hormones leptin and ghrelin. We have previously demonstrated that chronic ES reduces circulating leptin and alters adipose tissue metabolism early and later in life similarly in both sexes...
September 7, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28916968/hmgb-proteins-and-arthritis
#7
REVIEW
Noboru Taniguchi, Yasuhiko Kawakami, Ikuro Maruyama, Martin Lotz
The high-mobility group box (HMGB) family includes four members: HMGB1, 2, 3 and 4. HMGB proteins have two functions. In the nucleus, HMGB proteins bind to DNA in a DNA structure-dependent but nucleotide sequence-independent manner to function in chromatin remodeling. Extracellularly, HMGB proteins function as alarmins, which are endogenous molecules released upon tissue damage to activate the immune system. HMGB1 acts as a late mediator of inflammation and contributes to prolonged and sustained systemic inflammation in subjects with rheumatoid arthritis...
September 15, 2017: Human Cell
https://www.readbyqxmd.com/read/28916483/recombinant-humanized-anti-vascular-endothelial-growth-factor-monoclonal-antibody-efficiently-suppresses-laser-induced-choroidal-neovascularization-in-rhesus-monkeys
#8
Wan-Wan Ji, Dong-An Yu, Peng Yang, Peng Fang, Yu-Xia Cao, Hu Li, Ning Xie, Shou-Sheng Yan
Neovascular age-related macular degeneration, characterized by abnormal choroidal neovascularization (CNV), is a major cause of blindness worldwide. Anti-vascular endothelial growth factor (VEGF) antibodies have demonstrated significant efficacy in improving visual acuity. TMAB001 is a new recombinant humanized rabbit anti-VEGF monoclonal antibody. It presents high activities in vitro studies. In the binding affinity assay, TMAB001 exhibited a high binding capability to VEGF with an affinity constant of 10(-11)M...
September 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28916138/peptide-yy-induces-characteristic-meal-patterns-of-aged-mice
#9
Sachiko Mogami, Chihiro Yamada, Naoki Fujitsuka, Tomohisa Hattori
BACKGROUND & AIM: Changes in eating behavior occur in the elderly due to oral and swallowing dysfunctions. We aimed to clarify the difference between basal meal patterns of young and aged mice in relation to appetite regulating hormones. METHODS: Thirty two of young (7-week-old) and aged (23-25-month-old) C57BL/6 male mice were acclimated to a single housing and then transferred to a highly sensitive automated feeding monitoring device. Feeding behavior was monitored from the onset of the dark phase after habituation to the device...
September 12, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28915576/hepatic-b-cell-leukemia-3-suppresses-chemically-induced-hepatocarcinogenesis-in-mice-through-altered-mapk-and-nf-%C3%AE%C2%BAb-activation
#10
Nadine Gehrke, Marcus A Wörns, Amrit Mann, Yvonne Huber, Nadine Hoevelmeyer, Thomas Longerich, Ari Waisman, Peter R Galle, Jörn M Schattenberg
The transcriptional nuclear factor kappa B (NF-κB)-coactivator B cell leukemia-3 (Bcl-3) is a molecular regulator of cell death and proliferation. Bcl-3 has been shown to be widely expressed in different cancer types including hepatocellular carcinoma (HCC). Its influence on hepatocarcinogenesis is still undetermined. To examine the role of Bcl-3 in hepatocarcinogenesis mice with hepatocyte-specific overexpression of Bcl-3 (Bcl-3(Hep)) were exposed to diethylnitrosamine (DEN) and phenobarbital (PB). Hepatic Bcl-3 overexpression attenuated DEN/PB-induced hepatocarcinogenesis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915561/differentially-expressed-lncrnas-and-mirnas-with-associated-cerna-networks-in-aged-mice-with-postoperative-cognitive-dysfunction
#11
Changwei Wei, Ting Luo, Shanshan Zou, Xiaobin Zhou, Wenzhen Shen, Xiaolin Ji, Qi Li, Anshi Wu
Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients. Using microarray analyses, we comprehensively compared long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) expression profiles in hippocampal tissues from a mouse model of POCD and control mice. A total of 175 lncRNAs, 117 mRNAs, and 26 miRNAs were differentially expressed between POCD and control mice. Gene ontology (GO) and KEGG pathway enrichment analyses were performed to explore the principal functions of dysregulated genes...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915326/adaptive-immunity-and-metabolic-health-harmony-becomes-dissonant-in-obesity-and-aging
#12
Leena P Bharath, Blanche C Ip, Barbara S Nikolajczyk
Adipose tissue (AT) is the primary energy reservoir organ, and thereby plays a critical role in energy homeostasis and regulation of metabolism. AT expands in response to chronic overnutrition or aging and becomes a major source of inflammation that has marked influence on systemic metabolism. The chronic, sterile inflammation that occurs in the AT during the development of obesity or in aging contributes to onset of devastating diseases such as insulin resistance, diabetes, and cardiovascular pathologies. Numerous studies have shown that inflammation in the visceral AT of humans and animals is a critical trigger for the development of metabolic syndrome...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28913652/differences-in-bone-structure-and-unloading-induced-bone-loss-between-c57bl-6n-and-c57bl-6j-mice
#13
Jeyantt S Sankaran, Manasvi Varshney, Stefan Judex
The C57BL/6 mouse, the most frequently utilized animal model in biomedical research, is in use as several substrains, all of which differ by a small array of genomic differences. Two of these substrains, C57BL/6J (B6J) and C57BL/6N (B6N), are commonly used but it is unclear how phenotypically similar or different they are. Here, we tested whether adolescent B6N mice have a bone phenotype and respond to the loss of weightbearing differently than B6J. At 9 weeks of age, normally ambulating B6N had lower trabecular bone volume fraction but greater bone formation rates and osteoblast surfaces than corresponding B6J...
September 14, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28913408/hepatocyte-specific-deletion-of-mouse-lamin-a-c-leads-to-male-selective-steatohepatitis
#14
Raymond Kwan, Graham F Brady, Maria Brzozowski, Sujith V Weerasinghe, Hope Martin, Min-Jung Park, Makayla J Brunt, Ram K Menon, Xin Tong, Lei Yin, Colin L Stewart, M Bishr Omary
BACKGROUND & AIMS: Lamins are nuclear intermediate filament proteins that comprise the major components of the nuclear lamina. Mutations in LMNA, which encodes lamins A/C, cause laminopathies, including lipodystrophy, cardiomyopathy, and premature aging syndromes. However, the role of lamins in the liver is unknown, and it is unclear whether laminopathy-associated liver disease is caused by primary hepatocyte defects or systemic alterations. METHODS: To address these questions, we generated mice carrying a hepatocyte-specific deletion of Lmna (knockout [KO] mice) and characterized the KO liver and primary hepatocyte phenotypes by immunoblotting, immunohistochemistry, microarray analysis, quantitative real-time polymerase chain reaction, and Oil Red O and Picrosirius red staining...
November 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28912711/increased-hippocampal-probdnf-contributes-to-memory-impairments-in-aged-mice
#15
Mona Buhusi, Chris Etheredge, Ann-Charlotte Granholm, Catalin V Buhusi
Memory decline during aging or accompanying neurodegenerative diseases, represents a major health problem. Neurotrophins have long been considered relevant to the mechanisms of aging-associated cognitive decline and neurodegeneration. Mature Brain-Derived Neurotrophic Factor (BDNF) and its precursor (proBDNF) can both be secreted in response to neuronal activity and exert opposing effects on neuronal physiology and plasticity. In this study, biochemical analyses revealed that increased levels of proBDNF are present in the aged mouse hippocampus relative to young and that the level of hippocampal proBDNF inversely correlates with the ability to perform in a spatial memory task, the water radial arm maze (WRAM)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28912643/decreased-glial-gaba-and-tonic-inhibition-in-cerebellum-of-mouse-model-for-attention-deficit-hyperactivity-disorder-adhd
#16
Yoo Sung Kim, Junsung Woo, C Justin Lee, Bo-Eun Yoon
About 5~12% of school-aged children suffer from the Attention-Deficit/Hyperactivity Disorder (ADHD). However, the core mechanism of ADHD remains unclear. G protein-coupled receptor kinase-interacting protein-1 (GIT1) has recently been reported to be associated with ADHD in human and the genetic deletion of GIT1 result in ADHD-like behaviors in mice. Mice lacking GIT1 shows a shift in neuronal excitation/inhibition (E/I) balance. However, the pricise mechanism for E/I imbalance and the role of neuron-glia interaction in GIT1 knockout (KO) mice have not been studied...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28912581/secretory-phospholipase-a2-iia-overexpressing-mice-exhibit-cyclic-alopecia-mediated-through-aberrant-hair-shaft-differentiation-and-impaired-wound-healing-response
#17
Gopal L Chovatiya, Rahul M Sarate, Raghava R Sunkara, Nilesh P Gawas, Vineet Kala, Sanjeev K Waghmare
Secretory phospholipase A2 Group-IIA (sPLA2-IIA) is involved in lipid catabolism and growth promoting activity. sPLA2-IIA is deregulated in many pathological conditions including various cancers. Here, we have studied the role of sPLA2-IIA in the development of cyclic alopecia and wound healing response in relation to complete loss of hair follicle stem cells (HFSCs). Our data showed that overexpression of sPLA2-IIA in homozygous mice results in hyperproliferation and terminal epidermal differentiation followed by hair follicle cycle being halted at anagen like stage...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912521/advanced-glycation-end-product-age-albumin-from-activated-macrophage-is-critical-in-human-mesenchymal-stem-cells-survival-and-post-ischemic-reperfusion-injury
#18
Myeongjoo Son, Woong Chol Kang, Seyeon Oh, Delger Bayarsaikhan, Hyosang Ahn, Jaesuk Lee, Hyunjin Park, Sojung Lee, Junwon Choi, Hye Sun Lee, Phillip C Yang, Kyunghee Byun, Bonghee Lee
Post-ischemic reperfusion injury (PIRI) triggers an intense inflammatory response which is essential for repair but is also implicated in pathogenesis of post-ischemic remodeling in several organs in human. Stem cell therapy has recently emerged as a promising method for treatment of PIRI in human. However, satisfactory results have not been reported due to severe loss of injected stem cells in PIRI including critical limb ischemia (CLI). For investigating the advanced glycation end-product-albumin (AGE-albumin) from activated macrophages is critical in both muscle cell and stem cell death, we evaluated the recovery of PIRI-CLI by injection of human bone marrow derived mesenchymal stem cells (hBD-MSCs) with or without soluble receptor for AGEs (sRAGE)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912502/caloric-restriction-delays-age-related-methylation-drift
#19
Shinji Maegawa, Yue Lu, Tomomitsu Tahara, Justin T Lee, Jozef Madzo, Shoudan Liang, Jaroslav Jelinek, Ricki J Colman, Jean-Pierre J Issa
In mammals, caloric restriction consistently results in extended lifespan. Epigenetic information encoded by DNA methylation is tightly regulated, but shows a striking drift associated with age that includes both gains and losses of DNA methylation at various sites. Here, we report that epigenetic drift is conserved across species and the rate of drift correlates with lifespan when comparing mice, rhesus monkeys, and humans. Twenty-two to 30-year-old rhesus monkeys exposed to 30% caloric restriction since 7-14 years of age showed attenuation of age-related methylation drift compared to ad libitum-fed controls such that their blood methylation age appeared 7 years younger than their chronologic age...
September 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28912356/biomarkers-of-disease-can-be-detected-in-mice-as-early-as-4-weeks-after-initiation-of-exposure-to-third-hand-smoke-levels-equivalent-to-those-found-in-homes-of-smokers
#20
Neema Adhami, Yuxin Chen, Manuela Martins-Green
Third-hand smoke (THS) is a newly discovered environmental health hazard that results from accumulation and aging of second-hand smoke (SHS) toxins on surfaces where smoking has occurred. Our objective was to determine whether there is a time-dependent effect of THS exposure on health. Using an in vivo exposure mouse system that mimics exposure of humans to THS, we investigated its effects on biomarkers found in serum, and in liver and brain tissues. Mice were exposed to THS for 1, 2, 4, or 6 months and brain, liver, and serum were collected...
October 1, 2017: Clinical Science (1979-)
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