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cerebral spinal fluid mice

Jie Xu, Wu Zhang, Xiao-Jing Yan, Xue-Qiu Lin, Wei Li, Jian-Qing Mi, Jun-Min Li, Jiang Zhu, Zhu Chen, Sai-Juan Chen
BACKGROUND: DNMT3A mutations are frequently discovered in acute myeloid leukemia (AML), associated with poor outcome. Recently, a relapse case report of AML extramedullary disease has showed that AML cells harboring DNMT3A variation were detected in the cerebral spinal fluid. However, whether a causal relationship exists between DNMT3A mutation (D3Amut) and extramedullary infiltration (EMI) is unclear. METHODS: We took advantage of DNMT3A (R882C) mutation-carrying AML cell strain, that is, OCI-AML3, assessing its migration ability in vitro and in vivo...
October 10, 2016: Journal of Hematology & Oncology
Sophie Khazanov, Yael Paz, Amit Hefetz, Ben Jerry Gonzales, Yaara Netser, Abed AlFatah Mansour, Nissim Ben-Arie
During embryonic development of the central nervous system (CNS), the expression of the bHLH transcription factor Nato3 (Ferd3l) is unique and restricted to the floor plate of the neural tube. In mice lacking Nato3 the floor plate cells of the spinal cord do not fully maturate, whereas in the midbrain floor plate, progenitors lose some neurogenic activity, giving rise to a reduced population of dopaminergic neurons. Since the floor plate is considered to be disintegrated at the time of birth, Nato3 expression was never tested postnatally and in adult mice...
August 16, 2016: International Journal of Developmental Biology
Cristina García-Cáceres, Carmelo Quarta, Luis Varela, Yuanqing Gao, Tim Gruber, Beata Legutko, Martin Jastroch, Pia Johansson, Jovica Ninkovic, Chun-Xia Yi, Ophelia Le Thuc, Klara Szigeti-Buck, Weikang Cai, Carola W Meyer, Paul T Pfluger, Ana M Fernandez, Serge Luquet, Stephen C Woods, Ignacio Torres-Alemán, C Ronald Kahn, Magdalena Götz, Tamas L Horvath, Matthias H Tschöp
We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability...
August 11, 2016: Cell
C R Abraham, P C Mullen, T Tucker-Zhou, C D Chen, E Zeldich
In this chapter, we will describe what has been learned about Klotho and its potential functions in the brain. Klotho is localized in the choroid plexus and, to a lesser extent, in hippocampal neurons. Cognitive decline is a common issue in human aging affecting over 50% of the population. This cognitive decline can also be seen in animal models such as the Rhesus monkey. A long-term study undertaken by our lab demonstrated that normal brain aging in rhesus monkeys and other animal models is associated with a significant downregulation of Klotho expression...
2016: Vitamins and Hormones
Teng Jiang, Ying-Dong Zhang, Qi Chen, Qing Gao, Xi-Chen Zhu, Jun-Shan Zhou, Jian-Quan Shi, Huan Lu, Lan Tan, Jin-Tai Yu
As a novel risk gene for Alzheimer's disease (AD), triggering receptor expressed on myeloid cells 2 (TREM2) gene encodes a type I transmembrane receptor that is uniquely expressed by the microglia in the brain. Emerging evidence indicates a strong association between TREM2 and tau pathology in the cerebral spinal fluid or brain tissue of AD patients. In line with these clinical findings, we found that TREM2 was upregulated in the brain of P301S mice, an animal model of tau pathology, during disease progression...
June 2016: Neuropharmacology
Elizabeth Monreal-Escalante, Bernardo Bañuelos-Hernández, Marisela Hernández, Gladis Fragoso, Teresa Garate, Edda Sciutto, Sergio Rosales-Mendoza
Taenia solium cysticercosis is a major parasitic disease that affects the human health and the economy in underdeveloped countries. Porcine cysticercosis, an obligatory stage in the parasite life cycle, is a suitable target for vaccination. While several recombinant and synthetic antigens proved to be effective as vaccines, the cost and logistic difficulties have prevented their massive use. Taking this into account, a novel strategy for developing a multi-epitope low-cost vaccine is herein explored. The S3Pvac vaccine components (KETc1, KETc12, KETc7, and GK1 [KETc7]) and the protective HP6/TSOL18 antigen were expressed in a Helios2A polyprotein system, based on the 'ribosomal skip' mechanism mediated by the 2A sequence (LLNFDLLKLAGDVESNPG-P) derived from the Foot-and-mouth disease virus, which induces self-cleavage events at a translational level...
July 2015: Molecular Biotechnology
Yukiko Fujii, Tamon Niisoe, Kouji H Harada, Shinji Uemoto, Yasuhiro Ogura, Katsunobu Takenaka, Akio Koizumi
OBJECTIVES: Perfluoroalkyl carboxylic acids (PFCAs) consist of analogs with various carbon chain lengths. Their toxicokinetics have remained unexplored except in the case of perfluorooctanoic acid (8 carbon chemicals). This study aimed to investigate the toxicokinetics of PFCAs with six to fourteen carbon atoms (C6 to C14) in mice and humans. METHODS: We applied a two-compartment model to mice administered PFCAs intravenously or by gavage. The time courses of the serum concentration and tissue distribution and elimination were evaluated for 24 hours after treatment...
2015: Journal of Occupational Health
Y Joy Yu, Jasvinder K Atwal, Yin Zhang, Raymond K Tong, Kristin R Wildsmith, Christine Tan, Nga Bien-Ly, Maria Hersom, Janice A Maloney, William J Meilandt, Daniela Bumbaca, Kapil Gadkar, Kwame Hoyte, Wilman Luk, Yanmei Lu, James A Ernst, Kimberly Scearce-Levie, Jessica A Couch, Mark S Dennis, Ryan J Watts
Using therapeutic antibodies that need to cross the blood-brain barrier (BBB) to treat neurological disease is a difficult challenge. We have shown that bispecific antibodies with optimized binding to the transferrin receptor (TfR) that target β-secretase (BACE1) can cross the BBB and reduce brain amyloid-β (Aβ) in mice. Can TfR enhance antibody uptake in the primate brain? We describe two humanized TfR/BACE1 bispecific antibody variants. Using a human TfR knock-in mouse, we observed that anti-TfR/BACE1 antibodies could cross the BBB and reduce brain Aβ in a TfR affinity-dependent fashion...
November 5, 2014: Science Translational Medicine
Kathrin Meyer, Laura Ferraiuolo, Leah Schmelzer, Lyndsey Braun, Vicki McGovern, Shibi Likhite, Olivia Michels, Alessandra Govoni, Julie Fitzgerald, Pablo Morales, Kevin D Foust, Jerry R Mendell, Arthur H M Burghes, Brian K Kaspar
Spinal muscular atrophy (SMA) is the most frequent lethal genetic neurodegenerative disorder in infants. The disease is caused by low abundance of the survival of motor neuron (SMN) protein leading to motor neuron degeneration and progressive paralysis. We previously demonstrated that a single intravenous injection (IV) of self-complementary adeno-associated virus-9 carrying the human SMN cDNA (scAAV9-SMN) resulted in widespread transgene expression in spinal cord motor neurons in SMA mice as well as nonhuman primates and complete rescue of the disease phenotype in mice...
March 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
Lara S Hwa, Akiko Shimamoto, Tala Kayyali, Kevin J Norman, Rita J Valentino, Joseph F DeBold, Klaus A Miczek
Both the opioid antagonist naltrexone and corticotropin-releasing factor type-1 receptor (CRF-R1) antagonists have been investigated for the treatment of alcoholism. The current study examines the combination of naltrexone and CP154526 to reduce intermittent access ethanol drinking [intermittent access to alcohol (IAA)] in C57BL/6J male mice, and if these compounds reduce drinking via serotonergic mechanisms in the dorsal raphe nucleus (DRN). Systemic injections and chronic intracerebroventricular infusions of naltrexone, CP154526 or CP376395 transiently decreased IAA drinking...
January 2016: Addiction Biology
Neil R Marshall, Sofia Hassiotis, Barbara King, Tina Rozaklis, Paul J Trim, Stephen K Duplock, Leanne K Winner, Helen Beard, Marten F Snel, Robert D Jolly, John J Hopwood, Kim M Hemsley
Injection of lysosomal enzyme into cisternal or ventricular cerebrospinal fluid (CSF) has been carried out in 11 lysosomal storage disorder models, with each study demonstrating reductions in primary substrate and secondary neuropathological changes, and several reports of improved neurological function. Whilst acute studies in mucopolysaccharidosis (MPS) type II mice revealed that intrathecally-delivered enzyme (into thoraco-lumbar CSF) accesses the brain, the impact of longer-term treatment of affected subjects via this route is unknown...
January 2015: Experimental Neurology
Chen-Geng Liu, Jing Song, Yue-Qi Zhang, Pei-Chang Wang
Amyloid precursor protein (APP) has an important function in the generation of Alzheimer's disease (AD). In our previous study, miR‑193b was found to be downregulated in the hippocampi of 9‑month‑old APP/PS1 double‑transgenic mice using microRNA (miR) array. In the present study, bioinformatic analyses showed that miR‑193b was a miR that was predicted to potentially target the 3'‑untranslated region (UTR) of APP. Subsequently, the function of miR‑193b on APP was studied. The levels of miR‑193b, exosomal miR‑193b, Aβ, tau, p‑tau, HCY and APOE in samples from APP/PS1 double‑transgenic mice, mild cognitive impairment (MCI) and dementia of Alzheimer‑type (DAT) patients, were measured...
November 2014: Molecular Medicine Reports
Casmir Turnquist, Yihua Wang, David T Severson, Shan Zhong, Bin Sun, Jingyi Ma, Stefan N Constaninescu, Olaf Ansorge, Helen B Stolp, Zoltán Molnár, Francis G Szele, Xin Lu
Inflammation and loss of cell polarity play pivotal roles in neurodegeneration and cancer. A central question in both diseases is how the loss of cell polarity is sensed by cell death machinery. Here, we identify apoptosis-stimulating protein of p53 with signature sequences of ankyrin repeat-, SH3 domain-, and proline-rich region-containing protein 2 (ASPP2), a haploinsufficient tumor suppressor, activator of p53, and regulator of cell polarity, as a transcriptional target of signal transducer and activator of transcription 1 (STAT1)...
July 8, 2014: Proceedings of the National Academy of Sciences of the United States of America
Chen-Geng Liu, Jin-Ling Wang, Lei Li, Pei-Chang Wang
Amyloid precursor protein (APP) and β-site APP cleaving enzyme (BACE-1) play important roles in the pathogenesis of Alzheimer's disease (AD). In this study, using bioinformatics analysis, we demonstrate that miR-384 is a microRNA (miRNA or miR) predicted to potentially target the 3' untranslated regions (3'-UTRs) of both APP and BACE-1. SH-SY5Y cells were transfected with miR-384 mimic oligonucleotide, miR-384 inhibitor oligonucleotide, or a non-specific control siRNA. We found that the overexpression of miR-384 suppressed the mRNA and protein expression of both APP and BACE-1...
July 2014: International Journal of Molecular Medicine
Peng-Fei Wang, Huang Fang, Jing Chen, Sen Lin, Yong Liu, Xiao-Yi Xiong, Yan-Chun Wang, Ren-Ping Xiong, Feng-Lin Lv, Jian Wang, Qing-Wu Yang
Recent reports have shown that preconditioning with the TLR3 ligand polyinosinic-polycytidylic acid (poly(I:C)) protects against cerebral ischemia/reperfusion (I/R) injury. However, it is unclear whether poly(I:C) treatment after cerebral I/R injury is also effective. We used mouse/rat middle cerebral artery occlusion and cell oxygen-glucose deprivation models to evaluate the therapeutic effects and mechanisms of poly(I:C) treatment. Poly(I:C) was i.p. injected 3 h after ischemia (treatment group). Cerebral infarct volumes and brain edemas were significantly reduced, and neurologic scores were significantly increased...
May 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
David A Borkholder, Xiaoxia Zhu, Robert D Frisina
Delivery of therapeutic compounds to the inner ear via absorption through the round window membrane (RWM) has advantages over direct intracochlear infusions; specifically, minimizing impact upon functional hearing measures. However, previous reports show that significant basal-to-apical concentration gradients occur, with the potential to impact treatment efficacy. Here we present a new approach to inner ear drug delivery with induced advection aiding distribution of compounds throughout the inner ear in the murine cochlea...
January 28, 2014: Journal of Controlled Release: Official Journal of the Controlled Release Society
Kyle B Fraser, Mark S Moehle, João P L Daher, Philip J Webber, Jeri Y Williams, Carrie A Stewart, Talene A Yacoubian, Rita M Cowell, Terje Dokland, Tong Ye, Dongquan Chen, Gene P Siegal, Robert A Galemmo, Elpida Tsika, Darren J Moore, David G Standaert, Kyoko Kojima, James A Mobley, Andrew B West
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset Parkinson's disease (PD). Emerging evidence suggests a role for LRRK2 in the endocytic pathway. Here, we show that LRRK2 is released in extracellular microvesicles (i.e. exosomes) from cells that natively express LRRK2. LRRK2 localizes to collecting duct epithelial cells in the kidney that actively secrete exosomes into urine. Purified urinary exosomes contain LRRK2 protein that is both dimerized and phosphorylated. We provide a quantitative proteomic profile of 1673 proteins in urinary exosomes and find that known LRRK2 interactors including 14-3-3 are some of the most abundant exosome proteins...
December 15, 2013: Human Molecular Genetics
Xiaoqing Hu, Yuxuan Ji, Mingliang Wang, Fei Miao, Hongmei Ma, Hebai Shen, Nengqin Jia
The uniform-sized manganese oxide nanoparticles (the oleic-capped MnO NPs) were synthesized by the thermal decomposition of Mn-oleate complex and were transferred into water with the help of cationic surfactant of cetyltrimethyl ammonium bromide (CTAB), then the poly(vinylpyrrolidone) (PVP) membrane was further coated on to them with the aid of anionic dispersant of poly(styrenesulfonate) (PSS) by layer-by-layer electrostatic assembly to render them water soluble and biocompatible. They were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) and MTT assay...
June 2013: Journal of Biomedical Nanotechnology
Sjoerd A A van den Berg, Mattijs M Heemskerk, Janine J Geerling, Jan-Bert van Klinken, Frank G Schaap, Silvia Bijland, Jimmy F P Berbée, Vanessa J A van Harmelen, Amanda C M Pronk, Marijke Schreurs, Louis M Havekes, Patrick C N Rensen, Ko Willems van Dijk
Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the low APOA5 plasma abundance, we investigated an additional signaling role for APOA5 in high-fat diet (HFD)-induced obesity. Wild-type (WT) and Apoa5(-/-) mice fed a chow diet showed no difference in body weight or 24-h food intake (Apoa5(-/-), 4...
August 2013: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Mauro W Zappaterra, Anthony S LaMantia, Christopher A Walsh, Maria K Lehtinen
The CSF is a complex fluid with a dynamically varying proteome throughout development and in adulthood. During embryonic development, the nascent CSF differentiates from the amniotic fluid upon closure of the anterior neural tube. CSF volume then increases over subsequent days as the neuroepithelial progenitor cells lining the ventricles and the choroid plexus generate CSF. The embryonic CSF contacts the apical, ventricular surface of the neural stem cells of the developing brain and spinal cord. CSF provides crucial fluid pressure for the expansion of the developing brain and distributes important growth promoting factors to neural progenitor cells in a temporally-specific manner...
2013: Journal of Visualized Experiments: JoVE
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