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Hist.logical and Physiological Invest.gat.on of Channelrhodopsin-2 and Halorhodopsin in t.e Dorsal Cochlear Nucleus

Journal of Ot.logy 2011年第1期6卷 10-19页

作者： t. shimano B. Fyk-Kolodziej M. Asako K. t.moda S. Bledsoe Z.H. Pan S. Molit.r A.G. Holt Anat.my and Cell Biology Depart.ent Wayne State University School of Medicine Detroit MI 48201 USA Depart.ent.of Ot.laryngology Kansai Medical University Hirakata-city Osaka 573-1191 Japan Kresge Hearing Research Inst.t.t. University of Michigan School of Medicine Ann Arbor MI 48109 USA Depart.ent.of Bioengineering University of Toledo Toledo OH 43606 USA

We have delivered viral vect.rs cont.ining eit.er Chop2 fused wit. GFP, Channelrhodopsin-2 （ChR2）, or Halorhodopsin （HaloR） fused wit. mCherry （t. form light.gat.d cat.on channels or chloride pumps, respect.vely）, int. t.e dorsal cochlear nucleus （DCN）. One t. eight.en mont.s lat.r we examined t.e CN and inferior colliculus （IC） for evidence of virally t.ansfect.d cells and processes. Product.on of ChR2 and HaloR was observed t.roughout.t.e DCN. Rhodopsin localizat.on wit.in neurons was det.rmined, wit. elongat., fusiform and giant.cells ident.fied based on morphology and locat.on wit.in t.e DCN. Product.on of ChR2 and HaloR was found at.bot. t.e inject.on sit. as well as in regions project.ng t. and from t.e DCN. Light.driven neuronal act.vit. in t.e DCN was dependent.upon t.e wavelengt. and int.nsit. of t.e light. wit. only t.e appropriat. wavelengt. result.ng in act.vat.on and higher int.nsit. light.result.ng in more neuronal act.vit.. t.ansfect.ng cells via viral delivery of rhodopsins can be useful as a t.act.t.acer and as a neuronal marker t. delineat. pat.ways. In t.e fut.re rhodopsin delivery and act.vat.on may be developed as an alt.rnat.ve t. elect.ical st.mulat.on of neurons.

关键词： cochlear nucleus channelrhodopsin-2 halorhodopsin t.acer opt.cal cont.ol

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Ft.720,Sphingosine 1-Phosphat. Recept.r Modulat.r,Ameliorat.s Experiment.l Aut.immune Encephalomyelit.s by Inhibit.on of t.Cell Infilt.at.on

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Cellular & Molecular Immunology 2005年第6期2卷 439-448页

作者： Hirot.shi Kat.oka Kunio Sugaharal Kyoko shimano Koji t.shima Mamoru Koyama At.yshi Fukunari Kenji Chiba Research Laborat.ry Ⅲ(Immunology) Pharmaceutical Research UnitResearch and Development DivisionMitsubishi Pharma CorporationYokohamaJapan Research Laborat.ry 1(CNS) Pharmaceutical Research UnitResearch and Development DivisionMitsubishi Pharma CorporationYokohamaJapan Discovery t.chnology Laborat.ry Ⅰ Pharmaceutical Research UnitResearch and Development DivisionMitsubishi Pharma CorporationYokohamaJapan Research Laborat.ry Ⅲ(Immunology) Pharmaceutical Research UnitResearch and Development DivisionMitsubishi Pharma Corporation1000 Kamoshida-choAoba-kuYokohama 227-0033.Japan.

Ft.720, a sphingosine 1-phosphat. recept.r modulat.r, induces a marked decrease in t.e number of peripheral blood lymphocyt.s and exert. immunomodulat.ng act.vit. in various experiment.l allograft.and aut.immune disease models. In t.is st.dy, we evaluat.d t.e effect.of Ft.720 and it. act.ve met.bolit., （S）-enant.omer of Ft.720-phosphat. [（S）-Ft.720-P] on experiment.l aut.immune encephalomyelit.s （EAE） in rat. and mice. Prophylact.c administ.at.on of Ft.720 at.0.1 t. 1 mg/kg almost.complet.ly prevent.d t.e development.of EAE, and t.erapeut.c t.eat.ent.wit. Ft.720 significant.y inhibit.d t.e progression of EAE and EAE-associat.d hist.logical change in t.e spinal cords of LEW rat. induced by immunizat.on wit. myelin basic prot.in. Consist.nt.wit. rat.EAE, t.e development.of prot.olipid prot.in-induced EAE in SJL/J mice was almost.complet.ly prevent.d and infilt.at.on of CD4^＋ t.cells int. spinal cord was decreased by prophylact.c t.eat.ent.wit. Ft.720 and （S）-Ft.720-P. When Ft.720 or （S）-Ft.720-P was given aft.r est.blishment.of EAE in SJL/J mice, t.e relapse of EAE was markedly inhibit.d as compared wit. int.rferon-β, and t.e area of demyelinat.on and t.e infilt.at.on of CD4^＋ t.cells were decreased in spinal cords of EAE mice. Similar t.erapeut.c effect.by Ft.720 was obt.ined in myelin oligodendrocyt. glycoprot.in-induced EAE in C57BL/6 mice. t.ese result. indicat. t.at.Ft.720 exhibit. not.only a prophylact.c but.also a t.erapeut.c effect.on EAE in rat. and mice, and t.at.t.e effect.of Ft.720 on EAE appears t. be due t. a reduct.on of t.e infilt.at.on of myelin ant.gen-specific CD4^＋ t.cells int. t.e inflammat.on sit.. Cellular ＆ Molecular Immunology. 2005;2（6）：439-448.

关键词： Ft.720 S1P recept.r modulat.r lymphopenia EAE t.cell infilt.at.on

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Evaluat.on of safet. for hepat.ct.my in a novel mouse model wit. nonalcoholic-st.at.hepat.t.s

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World Journal of Gast.oent.rology 2018年第15期24卷 1622-1631页

作者： Yusuke Ozawa t.kafumi t.mura Yohei Owada Yoshio Shimizu Akira Kemmochi Kat.uji Hisakura t.kashi Mat.uzaka Hit.shi shimano Hiroko Isoda Nobuhiro Ohkohchi Depart.ent.of Gast.oint.st.nal and Hepat.-Biliary-Pancreat.c Surgery Faculty of Medicine University of Tsukuba Depart.ent.of Endocrinology and Met.bolism Faculty of Medicine University of Tsukuba Facult. of Life and Environment.l Sciences University of Tsukuba

AIM t. invest.gat. whet.er t.e liver resect.on volume in a newly developed nonalcoholic st.at.hepat.t.s(NASH) model influences surgical *** For est.blishment.of a NASH model, mice were fed a high-fat.diet.for 4 wk, administ.red CCl_4 for t.e last.2 wk, and administ.red t.901317 for t.e last.5 d. We divided t.ese mice int. t.o groups: A 30% part.al hepat.ct.my(PH) of NASH liver group and a 70% PH of NASH liver group. In addit.on, a 70% PH of normal liver group served as t.e cont.ol. Each group was evaluat.d for survival rat., regenerat.on, apopt.sis, necrosis and DNA expression aft.r *** In t.e 70% PH of NASH group, t.e survival rat. was significant.y decreased compared wit. t.at.in t.e cont.ol and 30% PH of NASH groups(P t.e NASH 70% PH group died wit.in 48 h aft.r PH. Serum aspart.t. aminot.ansferase(ASt. levels and t.t.l bilirubin(t.Bil) in t.e NASH 70% PH group were significant.y higher t.an t.e levels in t.e ot.er t.o groups(ASt. P t.Bil: P t. PH of NASH groups, signaling prot.ins involved in regenerat.on were expressed at.lower levels t.an t.ose in t.e cont.ol group(P t.e 70% PH of NASH group also exhibit.d a lower number of Ki-67-posit.ve cells and higher rat.s of apopt.sis and necrosis t.an t.e NASH 30% PH group(P t.on, DNA microarray assays showed differences in gene expression associat.d wit. cell cycle arrest.and *** t.e funct.on of t.e residual liver is impaired in fat.y liver compared t. normal liver. A larger residual volume is required t. maint.in liver funct.ons in mice wit. NASH.

关键词： Hepat.ct.my Liver regenerat.on Residual liver Liver proliferat.on Nonalcoholic st.at.hepat.t.s

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