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https://www.readbyqxmd.com/read/28449397/differential-proteome-profiling-in-the-hippocampus-of-amnesic-mice
#1
Meghraj Singh Baghel, Mahendra Kumar Thakur
Amnesia or memory loss is associated with brain aging and several neurodegenerative pathologies including Alzheimer's disease (AD). This can be induced by a cholinergic antagonist scopolamine, but the underlying molecular mechanism is poorly understood. The present study of proteome profiling in the hippocampus could provide conceptual insights into the molecular mechanisms involved in amnesia. To reveal this, mice were administered scopolamine to induce amnesia and memory impairment was validated by novel object recognition test...
April 27, 2017: Hippocampus
https://www.readbyqxmd.com/read/28448685/adult-neurobehavioral-alterations-in-male-and-female-mice-following-developmental-exposure-to-paracetamol-acetaminophen-characterization-of-a-critical-period
#2
Gaëtan Philippot, Torsten Gordh, Anders Fredriksson, Henrik Viberg
Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected...
April 27, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28448551/characterization-of-physiological-defects-in-adult-sirt6-mice
#3
Victoria Peshti, Alexey Obolensky, Liat Nahum, Yariv Kanfi, Moran Rathaus, Maytal Avraham, Simon Tinman, Fredrick W Alt, Eyal Banin, Haim Y Cohen
The NAD+-dependent SIRT6 deacetylase was shown to be a major regulator of lifespan and healthspan. Mice deficient for SIRT6 develop a premature aging phenotype and metabolic defects, and die before four weeks of age. Thus, the effect of SIRT6 deficiency in adult mice is unknown. Here we show that SIRT6-/- mice in mixed 129/SvJ/BALB/c background reach adulthood, allowing examination of SIRT6-related metabolic and developmental phenotypes in adult mice. In this mixed background, at 200 days of age, more than 80% of the female knock-out mice were alive whereas only 10% of male knock-out mice survived...
2017: PloS One
https://www.readbyqxmd.com/read/28448089/bone-degeneration-and-its-recovery-in-smp30-gnl-knockout-mice
#4
K Nishijima, T Ohno, A Amano, Y Kishimoto, Y Kondo, A Ishigami, S Tanaka
Senescence marker protein-30 (SMP30) decreases androgen-independently with aging and is a lactone-hydrolyzing enzyme gluconolactonase (GNL) that is involved in vitamin C biosynthesis. In the present study, bone properties of SMP30/GNL knockout (KO) mice with deficiency in vitamin C synthesis were investigated to reveal the effects of SMP30/GNL and exogenous vitamin C supplementation on bone formation. Mineral content (BMC) and mineral density (BMD) of the mandible and femur of SMP30/GNL KO and wild-type mice at 2 and 3 months of age with or without vitamin C supplementation were measured by dual-energy X-ray absorptiometry...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28448035/bioluminescence-imaging-of-neuroinflammation-in-transgenic-mice-after-peripheral-inoculation-of-alpha-synuclein-fibrils
#5
Sara Breid, Maria E Bernis, Julius B Tachu, Maria C Garza, Holger Wille, Gültekin Tamgüney
To study the prion-like behavior of misfolded alpha-synuclein, mouse models are needed that allow fast and simple transmission of alpha-synuclein prionoids, which cause neuropathology within the central nervous system (CNS). Here we describe that intraglossal or intraperitoneal injection of alpha-synuclein fibrils into bigenic Tg(M83(+/-):Gfap-luc(+/-)) mice, which overexpress human alpha-synuclein with the A53T mutation from the prion protein promoter and firefly luciferase from the promoter for glial fibrillary acidic protein (Gfap), is sufficient to induce neuropathologic disease...
April 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447205/treatment-with-geranylgeranylacetone-induces-heat-shock-protein-70-and-attenuates-neonatal-hyperoxic-lung-injury-in-a-model-of-bronchopulmonary-dysplasia
#6
Shuko Tokuriki, Aiko Igarashi, Takashi Okuno, Genrei Ohta, Hironobu Naiki, Yusei Ohshima
PURPOSE: Bronchopulmonary dysplasia (BPD) is a respiratory complication characterized by abnormal alveolar development in premature infants. Geranylgeranylacetone (GGA) can induce heat shock protein (HSP) 70, which has cytoprotective effects against various stressors. Here, we investigated whether GGA protected neonatal lungs from hyperoxic stress in a murine BPD model, and measured the serum HSP70 levels in preterm humans treated with oxygen. METHODS: Newborn mice were exposed to >90% oxygen and administered GGA or vehicle alone orally on days 1, 2, and 3 of life...
April 26, 2017: Lung
https://www.readbyqxmd.com/read/28446632/dietary-methionine-restriction-regulates-liver-protein-synthesis-and-gene-expression-independently-of-eukaryotic-initiation-factor-2-phosphorylation-in-mice
#7
Ashley P Pettit, William O Jonsson, Albert R Bargoud, Emily T Mirek, Frederick F Peelor, Yongping Wang, Thomas W Gettys, Scot R Kimball, Benjamin F Miller, Karyn L Hamilton, Ronald C Wek, Tracy G Anthony
Background: The phosphorylation of eukaryotic initiation factor 2 (p-eIF2) during dietary amino acid insufficiency reduces protein synthesis and alters gene expression via the integrated stress response (ISR).Objective: We explored whether a Met-restricted (MR) diet activates the ISR to reduce body fat and regulate protein balance.Methods: Male and female mice aged 3-6 mo with either whole-body deletion of general control nonderepressible 2 (Gcn2) or liver-specific deletion of protein kinase R-like endoplasmic reticulum kinase (Perk) alongside wild-type or floxed control mice were fed an obesogenic diet sufficient in Met (0...
April 26, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28446426/the-ablation-of-s1p3-receptor-protects-mouse-soleus-from-age-related-drop-of-muscle-mass-force-and-regenerative-capacity
#8
Michela Bondi, Elena Germinario, Marco Pirazzini, Giulia Zanetti, Francesca Cencetti, Chiara Donati, Luisa Gorza, Romeo Betto, Paola Bruni, Daniela Danieli-Betto
We investigated the effects of S1P3 deficiency on the age-related atrophy, decline of force and regenerative capacity of soleus muscle from 23-month-old male mice. During ageing, in old wild type mice, soleus mass and muscle fiber cross-sectional area (CSA) were reduced by about 26% and 24%, respectively, compared to the adult muscle. By contrast, the mass and fiber CSA of old S1P3-null soleus were comparable to the adult muscle. Moreover, in wild type soleus twitch and tetanic tensions diminished from adult to old age...
April 26, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28445460/polyglutamine-tracts-regulate-beclin-1-dependent-autophagy
#9
Avraham Ashkenazi, Carla F Bento, Thomas Ricketts, Mariella Vicinanza, Farah Siddiqi, Mariana Pavel, Ferdinando Squitieri, Maarten C Hardenberg, Sara Imarisio, Fiona M Menzies, David C Rubinsztein
Nine neurodegenerative diseases are caused by expanded polyglutamine (polyQ) tracts in different proteins, such as huntingtin in Huntington's disease and ataxin 3 in spinocerebellar ataxia type 3 (SCA3). Age at onset of disease decreases with increasing polyglutamine length in these proteins and the normal length also varies. PolyQ expansions drive pathogenesis in these diseases, as isolated polyQ tracts are toxic, and an N-terminal huntingtin fragment comprising exon 1, which occurs in vivo as a result of alternative splicing, causes toxicity...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445139/pannexin1-knockout-and-blockade-reduces-ischemic-stroke-injury-in-female-but-not-in-male-mice
#10
Moises Freitas-Andrade, John F Bechberger, Brian A MacVicar, Victor Viau, Christian C Naus
The membrane channel Pannexin 1 (Panx1) mediates apoptotic and inflammatory signaling cascades in injured neurons, responses previously shown to be sexually dimorphic under ischemic conditions. We tested the hypothesis that Panx1 plays an underlying role in mediating sex differences in stroke outcome responses. Middle-aged, 8-9 month old male and female wild type and Panx1 KO mice were subjected to permanent middle cerebral artery (MCA) occlusion, and infarct size and astrocyte and microglia activation were assessed 4 days later...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445087/cardioprotection-by-mild-hypothermia-is-abolished-in-aged-mice
#11
Junjie Guo, Shuning Zhang, Leilei Ma, Hongtao Shi, Jianbing Zhu, Jian Wu, Yi An, Junbo Ge
Mild hypothermia (MH) renders the hearts resistant to ischemia/reperfusion (IR) injury in animal experiments. Unexpectedly, this effect was not observed in recent clinical trials. The aged hearts in mice have been demonstrated to be more susceptible to IR injury. This study aimed to examine whether the cardioprotection of MH was abolished in aged mice. Young (Y, 3 months old) and aged (A, 20 months old) male C57BL/6 mice were randomized into six groups. Sham (Y-SHAM and A-SHAM) and control (Y-CON+IR and A-CON+IR) animals maintained core body temperature at 37°C ± 0...
April 26, 2017: Therapeutic Hypothermia and Temperature Management
https://www.readbyqxmd.com/read/28442885/complement-c5a-receptor-knockout-has-diminished-light-induced-microglia-macrophage-retinal-migration
#12
Delu Song, Michael E Sulewski, Chenguang Wang, Jiantao Song, Rupak Bhuyan, Jacob Sterling, Esther Clark, Wen-Chao Song, Joshua L Dunaief
PURPOSE: The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. METHODS: We assessed the effect of anaphylatoxin C3a receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced migration of microglia/macrophages into the mouse outer retina via immunofluorescence and real-time quantitative PCR...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28441664/protection-against-legionnaire-s-disease-recombinant-flagellin-a-of-legionella-pneumophila-can-induce-protective-immunity-against-bacteremia-in-a-balb-c-murine-model
#13
Ashraf Mohabati Mobarez, Roya Ahmadrajabi, Nima Khoramabadi, Ali-Hatef Salmanian
To investigate the immunoprotective effects of the recombinant type A flagellin (FLA), the flaA gene of Legionella pneumophila serogroup 1 strain Paris was cloned into pET28a(+). Recombinant FLA (rFLA) was overexpressed in E. coli BL21 (DE3) and purified by Ni2+ exchange chromatography. Female BALB/c aged 6-8 weeks were immunized with 20 μg of rFLA. Nonimmunized mice along with mice inoculated with a sublethal dose of live L. pneumophila intravenously were considered as negative and positive controls, respectively...
April 26, 2017: Journal of Molecular Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28441414/regional-early-and-progressive-loss-of-brain-pericytes-but-not-vascular-smooth-muscle-cells-in-adult-mice-with-disrupted-platelet-derived-growth-factor-receptor-%C3%AE-signaling
#14
Angeliki Maria Nikolakopoulou, Zhen Zhao, Axel Montagne, Berislav V Zlokovic
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain...
2017: PloS One
https://www.readbyqxmd.com/read/28441076/a-novel-neuroprotective-small-molecule-for-glial-cell-derived-neurotrophic-factor-induction-and-photoreceptor-rescue
#15
Petr Baranov, Hong Lin, Kathryn McCabe, David Gale, Shenshen Cai, Burke Lieppman, Dwight Morrow, Phoebe Lei, Justin Liao, Michael Young
PURPOSE: Degenerative diseases of the retina, such as retinitis pigmentosa and age-related macular degeneration, are characterized by the irreversible loss of photoreceptors. Several growth factors, including glial cell derived neurotrophic factor (GDNF), have been shown to rescue retinal neurons. An alternative strategy to direct GDNF administration is its induction in host retina by small molecules. Here we studied the ability of a novel small molecule GSK812 to induce GDNF in vitro/in vivo and rescue photoreceptors...
April 25, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28439667/myricetin-induced-brown-adipose-tissue-activation-prevents-obesity-and-insulin-resistance-in-db-db-mice
#16
Tao Hu, Xiaoxue Yuan, Gang Wei, Haoshu Luo, Hyuek Jong Lee, Wanzhu Jin
PURPOSE: Myricetin, a dietary flavonoid, is effective in the treatment of obesity and insulin resistance by increasing glucose transport and lipogenesis in adipocyte and diminishing systemic inflammation in obesity. However, it has not been revealed yet whether myricetin is associated with brown adipose tissue (BAT) activation that tightly mediates systemic energy metabolism. Therefore, this study assessed whether myricetin activated brown adipose tissue in db/db mouse. METHODS: Myricetin (400 mg/kg) in distilled water was fed daily by oral gavage to leptin receptor-deficient db/db male mice at 4 weeks of age for 14 weeks...
April 24, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28439080/ets-related-gene-mediated-androgen-receptor-aggregation-and-endoplasmic-reticulum-stress-in-prostate-cancer-development
#17
Taduru L Sreenath, Shiela S Macalindong, Natallia Mikhalkevich, Shashwat Sharad, Ahmed Mohamed, Denise Young, Talaibek Borbiev, Charles Xavier, Rishita Gupta, Muhammad Jamal, Kevin Babcock, Shyh-Han Tan, Marja T Nevalainen, Albert Dobi, Gyorgy Petrovics, Isabell A Sesterhenn, Inger L Rosner, Charles J Bieberich, Peter Nelson, Valeri Vasioukhin, Shiv Srivastava
Mechanistic studies of deregulated ERG in prostate cancer and other cancers continue to enhance its role in cancer biology and its utility as a biomarker and therapeutic target. Here, we show that ERG, through its physical interaction with androgen receptor, induces AR aggregation and endoplasmic reticulum stress in the prostate glands of ERG transgenic mice. Histomorphological alterations and the expression of ER stress sensors Atf6, Ire1α, Perk, their downstream effectors Grp78/BiP and eIF2α in ERG transgenic mouse prostate glands indicate the presence of chronic ER stress...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439009/estrogen-receptor-%C3%AE-a-regulator-of-androgen-receptor-signaling-in-the-mouse-ventral-prostate
#18
Wan-Fu Wu, Laure Maneix, Jose Insunza, Ivan Nalvarte, Per Antonson, Juha Kere, Nancy Yiu-Lin Yu, Virpi Tohonen, Shintaro Katayama, Elisabet Einarsdottir, Kaarel Krjutskov, Yu-Bing Dai, Bo Huang, Wen Su, Margaret Warner, Jan-Åke Gustafsson
As estrogen receptor β(-/-) (ERβ(-/-)) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young (2-mo-old) and aging (18-mo-old) ERβ(-/-) mice and their WT littermates. We also treated young and old WT mice with an ERβ-selective agonist and evaluated protein expression. The most significant findings were that ERβ down-regulates androgen receptor (AR) signaling and up-regulates the tumor suppressor phosphatase and tensin homolog (PTEN)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438992/microglial-nf%C3%AE%C2%BAb-tnf%C3%AE-hyperactivation-induces-obsessive-compulsive-behavior-in-mouse-models-of-progranulin-deficient-frontotemporal-dementia
#19
Grietje Krabbe, S Sakura Minami, Jon I Etchegaray, Praveen Taneja, Biljana Djukic, Dimitrios Davalos, David Le, Iris Lo, Lihong Zhan, Meredith C Reichert, Faten Sayed, Mario Merlini, Michael E Ward, David C Perry, Suzee E Lee, Ana Sias, Christopher N Parkhurst, Wen-Biao Gan, Katerina Akassoglou, Bruce L Miller, Robert V Farese, Li Gan
Frontotemporal dementia (FTD) is the second most common dementia before 65 years of age. Haploinsufficiency in the progranulin (GRN) gene accounts for 10% of all cases of familial FTD. GRN mutation carriers have an increased risk of autoimmune disorders, accompanied by elevated levels of tissue necrosis factor (TNF) α. We examined behavioral alterations related to obsessive-compulsive disorder (OCD) and the role of TNFα and related signaling pathways in FTD patients with GRN mutations and in mice lacking progranulin (PGRN)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438970/the-severity-of-vestibular-dysfunction-in-deafness-as-a-determinant-of-comorbid-hyperactivity-or-anxiety
#20
Michelle W Antoine, Sarath Vijayakumar, Nicholas McKeehan, Sherri M Jones, Jean M Hébert
Attention-deficit/hyperactivity disorder (ADHD) and anxiety-related disorders occur at rates 2-3 times higher in deaf compared with hearing children. Potential explanations for these elevated rates and the heterogeneity of behavioral disorders associated with deafness have usually focused on socio-environmental rather than biological effects. Children with the 22q11.2 deletion or duplication syndromes often display hearing loss and behavioral disorders including ADHD and anxiety-related disorders. Here, we show that mouse mutants with either a gain- or loss-of-function of the T-Box transcription factor gene, Tbx1, which lies within the 22q11...
April 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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