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A bright future for the tree shrew in neuroscience research:Summary from the inaugural Tree Shrew Users Meeting

Zoological Research 2021年第4期42卷 478-481页

作者： Elise Savier Madineh Sedigh-Sarvestani ralf wimmer David Fitzpatrick University of Virginia CharlottesvilleVirginia 22903-1738USA Max Planck Florida Institute for Neuroscience JupiterFlorida 33458-2906USA Massachusetts Institute of Technology CambridgeMassachusetts 02139-4307USA

Tree shrews(Tupaia spp.)have been used in neuroscience research since the 1960s due to their evolutionary proximity to *** use of and interest in this animal model have recently increased,in part due to the adaptation of modern neuroscience tools in this *** tools include quantitative behavioral assays,calcium imaging,optogenetics and *** facilitate the exchange and development of these new technologies and associated research findings,we organized the inaugural“Tree Shrew Users Meeting”which was held online due to the COVID-19 ***,we review this meeting and discuss the history of tree shrews as an animal model in neuroscience research and summarize the current themes being investigated using this animal,as well as future directions.

关键词： Tree Shrew Users Meeting Animal models Tupaia Neuroscience

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Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model

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World Journal of Hepatology 2016年第8期8卷 401-410页

作者： Florian P Reiter ralf wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk Department of Medicine Ⅱ Liver Center Munich University of Munich Institute of Pathology University of Munich Department of Medicine Ⅰ Krankenhaus Barmherzige Brüder Research Unit for Experimental and Molecular Hepatology Division of Gastroenterology and Hepatology Department of Internal Medicine Hans Popper Laboratory of Molecular Hepatology Division of Gastroenterology and Hepatology Department of Internal Medicine Ⅲ Medical University of Vienna Transplant Center Munich of the University of Munich

AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse ***: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-te

关键词： Cholestasis Primary sclerosing cholangitis The ATP-binding cassette transporter b4 Liver fibrosis Interleukin-1

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