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https://www.readbyqxmd.com/read/28432138/inhibition-of-drp1-ameliorates-synaptic-depression-a%C3%AE-deposition-and-cognitive-impairment-in-alzheimer-s-disease-model
#1
Seung-Hyun Baek, So Jung Park, Jae In Jeong, Sung Hyun Kim, Jihoon Han, Jae Won Kyung, Sang-Ha Baik, Yuri Choi, Bo-Youn Choi, Jinsu Park, Gahee Bahn, Ji Hyun Shin, Doo Sin Jo, Joo-Yong Lee, Choon-Gon Jang, Thiruma V Arumugam, Jongpil Kim, Jeung-Whan Han, Jae-Young Koh, Dong-Hyung Cho, Dong-Gyu Jo
Excessive mitochondrial fission is a prominent early event, and contributes to mitochondrial dysfunction, synaptic failure and neuronal cell death in the progression of Alzheimer's disease (AD). However, it remains to be determined whether inhibition of excessive mitochondrial fission is beneficial in mammal models of AD. To determine whether dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fragmentation, can be a disease-modifying therapeutic target for AD, we examine the effects of Drp1 inhibitor on mitochondrial and synaptic dysfunctions induced by oligomeric β-amyloid (Aβ) in neurons, and neuropathology and cognitive functions in APP/PS1 double transgenic AD mice...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432106/prohibitin-induced-obesity-leads-to-anovulation-and-polycystic-ovary-in-mice
#2
Sudharsana Rao Ande, Khanh Hoa Nguyen, Yang Xin Zi Xu, Suresh Mishra
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and the most common cause of female infertility. However, the etiology of the disease and the mechanisms by which this disorder progress remain unclear. Here we report that a transgenic obese mouse (Mito-Ob) developed by overexpressing prohibitin in adipocytes develops polycystic ovaries. Initially, the female Mito-Ob mice were equally fertile to their wild-type littermates. Mito-Ob mice begin to gain weight after puberty, become significantly obese between 3-6 months of age, and roughly 25% of them become infertile by 9 months of age...
April 21, 2017: Biology Open
https://www.readbyqxmd.com/read/28432072/translocase-of-inner-membrane-50-functions-as-a-novel-protective-regulator-of-pathological-cardiac-hypertrophy
#3
Kai Tang, Yifan Zhao, Hailing Li, Mengyun Zhu, Weiming Li, Weijing Liu, Guofu Zhu, Dachun Xu, Wenhui Peng, Ya-Wei Xu
BACKGROUND: Translocase of inner membrane 50 (TIM50) is a member of the translocase of inner membrane (TIM) complex in the mitochondria. Previous research has demonstrated the role of TIM50 in the regulation of oxidative stress and cardiac morphology. However, the role of TIM50 in pathological cardiac hypertrophy remains unknown. METHODS AND RESULTS: In the present study we found that the expression of TIM50 was downregulated in hypertrophic hearts. Using genetic loss-of-function animal models, we demonstrated that TIM50 deficiency increased heart and cardiomyocyte size with more severe cardiac fibrosis compared with wild-type littermates...
April 21, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28432017/dual-functional-nanoparticles-for-precise-drug-delivery-to-alzheimer-s-disease-lesions-targeting-mechanisms-pharmacodynamics-and-safety
#4
Xiaoyao Zheng, Chi Zhang, Qian Guo, Xu Wan, Xiayan Shao, Qingfeng Liu, Qizhi Zhang
Alzheimer's disease (AD) is the most common form of dementia and is characterized by the cerebral accumulation of extracellular amyloid plaques. In a previous study, this histopathological hallmark was used as a target on a dual-functional nanoparticle (TQNP) to deliver biotechnological drugs, such as the H102 peptide, a β-sheet breaker, to AD lesions precisely. This delivery system could reduce the amyloid-β (Aβ) burden in the brains of AD model mice, as well as ameliorated the memory impairment of the mice...
April 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28431906/transgenic-mice-with-increased-astrocyte-expression-of-ccl2-show-altered-behavioral-effects-of-alcohol
#5
Jennifer G Bray, Amanda J Roberts, Donna L Gruol
Emerging research provides strong evidence that activation of CNS glial cells occurs in neurological diseases and brain injury and results in elevated production of neuroimmune factors. These factors can contribute to pathophysiological processes that lead to altered CNS function. Recently, studies have also shown that both acute and chronic alcohol consumption can produce activation of CNS glial cells and the production of neuroimmune factors, particularly the chemokine CCL2. The consequences of alcohol-induced increases in CCL2 levels in the CNS have yet to be fully elucidated...
April 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28431892/a-humanized-hla-dr4-mouse-model-for-autoimmune-myocarditis
#6
M Emrah Şelli, Anita C Thomas, David C Wraith, Andrew C Newby
Myocarditis, the principal cause of dilated cardiomyopathy and heart failure in young adults, is associated with autoimmunity to human cardiac α-myosin (hCAM) and the DR4 allele of human major histocompatibility II (MHCII). We developed an hCAM-induced myocarditis model in human HLA-DR4 transgenic mice that lack all mouse MHCII genes, demonstrating that immunization for 3weeks significantly increased splenic T-cell proliferative responses and titres of IgG1 and IgG2c antibodies, abolished weight gain, provoked cardiac inflammation and significantly impaired cardiac output and fractional shortening, by echocardiography, compared to adjuvant-injected mice...
April 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28431735/characterization-of-an-amyloid-only-transgenic-b6c3-tg-appswe-psen1de9-85dbo-mmjax-mouse-model-of-alzheimer-s-disease
#7
G S Finnie, R Gunnarsson, J Manavis, P C Blumbergs, K A Mander, S Edwards, C Van den Heuvel, J W Finnie
The spatiotemporal pattern of cerebral amyloid deposition, detectable as light microscopically recognizable aggregates in an 'amyloid only' transgenic mouse model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported for the first time in this strain. Monoclonal and polyclonal antibodies were used to detect amyloid deposition immunohistochemically in brains collected from these mice at 3-12 months of age. Amyloid aggregates (20-200 μm) were first found in serial, whole coronal sections of brain at 4 months of age and these increased progressively, plateauing at 11-12 months...
April 18, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28431562/effects-of-the-common-polymorphism-in-the-human-aldehyde-dehydrogenase-2-aldh2-gene-on-the-lung
#8
Aoi Kuroda, Ahmed E Hegab, Gao Jingtao, Shuji Yamashita, Nobuyuki Hizawa, Tohru Sakamoto, Hideyasu Yamada, Satoshi Suzuki, Makoto Ishii, Ho Namkoong, Takanori Asakura, Mari Ozaki, Hiroyuki Yasuda, Junko Hamamoto, Shizuko Kagawa, Kenzo Soejima, Tomoko Betsuyaku
BACKGROUND: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined...
April 21, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28430966/decreased-thromboembolic-stroke-but-not-atherosclerosis-or-vascular-remodeling-in-mice-with-rock2-deficient-platelets
#9
Nikola Sladojevic, Goo Taeg Oh, Hyung-Hwan Kim, Lea M Beaulieu, Hervé Falet, Karol Kaminski, Jane E Freedman, James K Liao
Aims: Rho-associated coiled-coil containing kinase (ROCK)-2 is an important mediator of the actin cytoskeleton. Because changes in the actin cytoskeleton are critical for platelet function, we hypothesized that ROCK2 in platelets will play important role in thrombosis and can be potentially a target for therapeutic intervention in thromboembolic stroke. Methods and Results: We generated platelet-specific ROCK2-deficient mice (ROCK2 Plt-/- ) from conditional ROCK2 fl°x/fl°x and platelet factor (PF)-4-Cre transgenic mice...
April 14, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430664/identification-of-a-novel-pd-l1-positive-solid-tumor-transplantable-in-hla-a-0201-drb1-0101-transgenic-mice
#10
Laurie Rangan, Jeanne Galaine, Romain Boidot, Mohamad Hamieh, Magalie Dosset, Julie Francoual, Laurent Beziaud, Jean-René Pallandre, Elodie Lauret Marie Joseph, Afag Asgarova, Christophe Borg, Talal Al Saati, Yann Godet, Jean Baptiste Latouche, Séverine Valmary-Degano, Olivier Adotévi
HLA-A*0201/DRB1*0101 transgenic mice (A2/DR1 mice) have been developed to study the immunogenicity of tumor antigen-derived T cell epitopes. To extend the use and application of this mouse model in the field of antitumor immunotherapy, we described a tumor cell line generated from a naturally occurring tumor in A2/DR1 mouse named SARC-L1. Histological and genes signature analysis supported the sarcoma origin of this cell line. While SARC-L1 tumor cells lack HLA-DRB1*0101 expression, a very low expression of HLA-A*0201 molecules was found on these cells...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430602/fluoxetine-attenuates-the-impairment-of-spatial-learning-ability-and-prevents-neuron-loss-in-middle-aged-appswe-psen1de9-double-transgenic-alzheimer-s-disease-mice
#11
Jing Ma, Yuan Gao, Lin Jiang, Feng-Lei Chao, Wei Huang, Chun-Ni Zhou, Wei Tang, Lei Zhang, Chun-Xia Huang, Yi Zhang, Yan-Min Luo, Qian Xiao, Hua-Rong Yu, Rong Jiang, Yong Tang
Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer's disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429406/haplodeficiency-of-cathepsin-d-does-not-affect-cerebral-amyloidosis-and-autophagy-in-app-ps1-transgenic-mice
#12
Shaowu Cheng, Willayat Y Wani, David A Hottman, Angela Jeong, Dongfeng Cao, Kyle J LeBlanc, Paul Saftig, Jianhua Zhang, Ling Li
Autophagy and lysosomal function are important for protein homeostasis and their dysfunction have been associated with Alzheimer's disease (AD). Increased immunoreactivities of an important lysosomal protease, cathepsin D (Cat D), are evident in amyloid plaques and neurons in patients with AD. The current study tests the hypothesis that deleting one allele of the cathepsin D gene (Ctsd) impacts cerebral β-amyloidosis in APPsw/PS1dE9 (APP/PS1) double transgenic mice. Despite a significant 38% decrease of Cat D level in APP/PS1/Ctsd+/- compared to APP/PS1/Ctsd+/+ mice, no changes in steady state levels and deposition of Aβ were found in the brain...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28428886/vaccination-with-inhibin-%C3%AE-provides-effective-immunotherapy-against-testicular-stromal-cell-tumors
#13
Robert Aguilar, Justin M Johnson, Patrick Barrett, Vincent K Tuohy
BACKGROUND: Testicular cancer is the most common male neoplasm occurring in men between the ages of 20 and 34. Although germ-line testicular tumors respond favorably to current standard of care, testicular stromal cell (TSC) tumors derived from Sertoli cells or Leydig cells often fail to respond to chemotherapy or radiation therapy and have a 5-year overall survival significantly lower than the more common and more treatable germ line testicular tumors. METHODS: To improve outcomes for TSC cancer, we have developed a therapeutic vaccine targeting inhibin-α, a protein produced by normal Sertoli and Leydig cells of the testes and expressed in the majority of TSC tumors...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428278/oncogenic-role-of-snd1-in-development-and-progression-of-hepatocellular-carcinoma
#14
Nidhi Jariwala, Devaraja Rajasekaran, Rachel G Mendoza, Xue-Ning Shen, Ayesha Siddiq, Maaged Akiel, Chadia L Robertson, Mark A Subler, Jolene Windle, Paul B Fisher, Arun J Sanyal, Devanand Sarkar
SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). In this study, we show that hepatocyte-specific SND1 transgenic mice (Alb/SND1 mice) develop spontaneous HCC with partial penetrance and exhibit more highly aggressive HCC induced by chemical carcinogenesis. Livers from Alb/SND1 mice exhibited a relative increase in inflammatory markers and spheroid-generating tumor initiating cells (TIC). Mechanistic investigations defined roles for Akt and NF-kappaB signaling pathways in promoting TIC formation in Alb/SND1 mice...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28426964/ipsc-derived-human-microglia-like-cells-to-study-neurological-diseases
#15
Edsel M Abud, Ricardo N Ramirez, Eric S Martinez, Luke M Healy, Cecilia H H Nguyen, Sean A Newman, Andriy V Yeromin, Vanessa M Scarfone, Samuel E Marsh, Cristhian Fimbres, Chad A Caraway, Gianna M Fote, Abdullah M Madany, Anshu Agrawal, Rakez Kayed, Karen H Gylys, Michael D Cahalan, Brian J Cummings, Jack P Antel, Ali Mortazavi, Monica J Carson, Wayne W Poon, Mathew Blurton-Jones
Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGLs) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426279/combination-of-gemcitabine-and-docetaxel-regress-both-gastric-leiomyosarcoma-proliferation-and-invasion-in-an-imageable-patient-derived-orthotopic-xenograft-ipdox-model
#16
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Tasuku Kiyuna, Scott D Nelson, Sarah M Dry, Yunfeng Li, Tara A Russell, Arun S Singh, Bartosz Chmielowski, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
Gastric leiomyosarcoma is a recalcitrant cancer and chemotherapy strategy is controversial. The present study used a patient-derived orthotopic xenograft (PDOX) nude mouse model of gastric leiomyosarcoma to identify an effective therapeutic regimen in order to develop individualized precision medicine for this disease. A gastric leiomyosarcoma obtained from a patient was first grown in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP) in order to stably label the tumor stroma. The RFP-expressing tumor was then passaged orthotopically in the gastric wall of non-transgenic nude mice to establish an imageable PDOX (iPDOX) model...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28425860/a-novel-recombinant-multi-epitope-vaccine-could-induce-specific-cytotoxic-t-lymphocyte-response-in-vitro-and-in-vivo
#17
Yahong Wu, Wenjie Zhai, Meng Sun, Zhe Zou, Xiuman Zhou, Guodong Li, Zhongyi Yan, Yuanming Qi, Yanfeng Gao
Cytotoxic T lymphocytes (CTLs) against various tumor antigens play an important role in elimination of tumor cells. To develop therapeutic vaccines that can induce specific immune response, we designed a novel recombinant multiepitope vaccine YL66 which consists of HLA-A2-restricted CTL epitopes from two widely expressed tumor antigen cyclooxygenase-2 and MAGE-4, linked with membrane permeable Tat-PTD and the universal T helper epitope. The DNA fragment of YL66 was cloned into pGEX-4T-2-YL66 and pcDNA3.1(+)-YL66, respectively...
April 19, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28425851/altered-structure-and-function-of-adipose-tissue-in-long-lived-mice-with-growth-hormone-related-mutations
#18
Justin Darcy, Samuel McFadden, Andrzej Bartke
A major focus of biogerontology is elucidating the role(s) of the endocrine system in aging and the accumulation of age-related diseases. Endocrine control of mammalian longevity was first reported in Ames dwarf (Prop1(df)) mice, which are long-lived due to a recessive Prop1 loss-of-function mutation resulting in deficiency of growth hormone (GH), thyroid-stimulating hormone, and prolactin. Following this report, several other GH-related mutants with altered longevity have been described including long-lived Snell dwarf and growth hormone receptor knockout mice, and short-lived GH overexpressing transgenic mice...
March 21, 2017: Adipocyte
https://www.readbyqxmd.com/read/28425492/fluorescence-and-bioluminescence-imaging-of-angiogenesis-in-flk1-nano-lantern-transgenic-mice
#19
Jun Matsushita, Shigenori Inagaki, Tomomi Nishie, Tomoki Sakasai, Junko Tanaka, Chisato Watanabe, Ken-Ichi Mizutani, Yoshihiro Miwa, Ken Matsumoto, Kazuhiro Takara, Hisamichi Naito, Hiroyasu Kidoya, Nobuyuki Takakura, Takeharu Nagai, Satoru Takahashi, Masatsugu Ema
Angiogenesis is important for normal development as well as for tumour growth. However, the molecular and cellular mechanisms underlying angiogenesis are not fully understood, partly because of the lack of a good animal model for imaging. Here, we report the generation of a novel transgenic (Tg) mouse that expresses a bioluminescent reporter protein, Nano-lantern, under the control of Fetal liver kinase 1 (Flk1). Flk1-Nano-lantern BAC Tg mice recapitulated endogenous Flk1 expression in endothelial cells and lymphatic endothelial cells during development and tumour growth...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28425451/ifn%C3%AE-protects-neurons-from-damage-in-a-murine-model-of-hiv-1-associated-brain-injury
#20
Victoria E Thaney, Alan M O'Neill, Melanie M Hoefer, Ricky Maung, Ana B Sanchez, Marcus Kaul
Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects...
April 20, 2017: Scientific Reports
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