ウイルスベクター開発研究センター発足後の成果
2024年
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Konno A, Shinohara Y, Hirai H.
Production of Spinocerebellar Ataxia Type 3 Model Mice by Intravenous Injection of AAV-PHP.B Vectors.
Int J Mol Sci. 2024, 25(13), 7205; https://doi.org/10.3390/ijms25137205
Kinoshita K, Motomura K, Ushida K, Hirata Y, Konno A, Hirai H, Kotani S, Hitora-Imamura N, Kurauchi Y, Seki T, Katsuki H.
Nurr1 overexpression in the primary motor cortex alleviates motor dysfunction induced by intracerebral hemorrhage in the striatum in mice
Neurotherapeutics. 2024 May 3:e00370. doi: 10.1016/j.neurot.2024.e00370. Online ahead of print.
Watanave M, Kawachi M, Konno A, Aoki R, Fukai Y, Matsuzaki Y, Kaneko R, Hirai H.
Protein kinase Cγ negatively regulates the intrinsic excitability in zebrin-negative cerebellar Purkinje cells
Front Cell Neurosci. 2024 Feb 16;18:1349878. doi: 10.3389/fncel.2024.1349878. eCollection 2024.
Tan W, Ikoma Y, Takahashi Y, Konno A, Hirai H, Hirase H, Matsui K.
Anxiety control by astrocytes in the lateral habenula.
Neurosci Res. 2024 Feb 2:S0168-0102(24)00010-5. doi: 10.1016/j.neures.2024.01.006. Online ahead of print.
Kawabata H, Konno A, Matsuzaki Y, Sato Y, Kawachi M, Aoki R, Tsutsumi S, Togai S, Kobayashi R, Horii T, Hatada I, Hirai H.
Improving cell-specific recombination using AAV vectors in the murine CNS by capsid and expression cassette optimization.
Mol Ther Methods Clin Dev. 2024 Jan 10. in press doi: 10.1016/j.omtm.2024.101185
2023年
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Morishima M, Matsumura S, Tohyama S, Nagashima T, Konno A, Hirai H, Watabe AM.
Excitatory subtypes of the lateral amygdala neurons are differentially involved in regulation of synaptic plasticity and excitation/inhibition balance in aversive learning in mice.
Front Cell Neurosci. 2023 Dec 14;17:1292822. doi: 10.3389/fncel.2023.1292822. eCollection 2023.
Nagashima T, Mikami K, Tohyama S, Konno A, Hirai H, Watabe AM.
State-dependent modulation of positive and negative affective valences by a parabrachial nucleus-to-ventral tegmental area pathway in mice.
Front Neural Circuits. 2023 Nov 29;17:1273322. doi: 10.3389/fncir.2023.1273322. eCollection 2023.
Ozawa K, Nagao M, Konno A, Iwai Y, Vittani M, Kusk P, Mishima T, Hirai H, Nedergaard M, Hirase H.
Astrocytic GPCR-Induced Ca2+ Signaling Is Not Causally Related to Local Cerebral Blood Flow Changes.
Int J Mol Sci. 2023 Sep 2;24(17):13590. doi: 10.3390/ijms241713590.
Murase S, Sakitani N, Maekawa T, Yoshino D, Takano K, Konno A, Hirai H, Saito T, Tanaka S, Shinohara K, Kishi T, Yoshikawa Y, Sakai T, Ayaori M, Inanami H, Tomiyasu K, Takashima A, Ogata T, Tsuchimochi H, Sato S, Saito S, Yoshino K, Matsuura Y, Funamoto K, Ochi H, Shinohara M, Nagao M, Sawada Y.
Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans.
Nat Biomed Eng. 2023 Nov;7(11):1350-1373. doi: 10.1038/s41551-023-01061-x. Epub 2023 Jul 6.
Ichinose S, Susuki Y, Hosoi N, Kaneko R, Ebihara M, Hirai H, Iwasaki H.
Interaction between Teneurin-2 and microtubules via EB proteins provides a platform for GABAA receptor exocytosis.
Elife. 2023 Jun 5;12:e83276. doi: 10.7554/eLife.83276.
Yaguchi K, Hagihara M, Konno A, Hirai H, Yukinaga H, Miyamichi K.
Dynamic modulation of pulsatile activities of oxytocin neurons in lactating wild-type mice.
PLoS One. 2023 May 10;18(5):e0285589. doi: 10.1371/journal.pone.0285589. eCollection 2023.
Kawabata H, Konno A, Matsuzaki Y, Hirai H.
A blood-brain barrier-penetrating AAV2 mutant created by a brain microvasculature endothelial cell-targeted AAV2 variant.
Mol Ther Methods Clin Dev. 2023 Mar 2;29:81-92. doi: 10.1016/j.omtm.2023.02.016. eCollection 2023 Jun 8.
Uggerud IM, Kråkenes T, Hirai H, Vedeler CA, Schubert M.
Development and Optimization of a Multilayer Rat Purkinje Neuron Culture.
Cerebellum. 2023 Jan 10. doi: 10.1007/s12311-022-01510-4. Online ahead of print.
2022年
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Jin M, Matsumoto S, Ayaki T, Yamakado H, Taguchi T, Togawa N, Konno A, Hirai H, Nakajima H, Komai S, Ishida R, Chiba S, Takahashi R, Takao T, Hirotsune S.
DOPAnization of tyrosine in α-synuclein by tyrosine hydroxylase leads to the formation of oligomers.
Nat Commun. 2022 Nov 12;13(1):6880. doi: 10.1038/s41467-022-34555-4.
Okada Y, Hosoi N, Matsuzaki Y, Fukai Y, Hiraga A, Nakai J, Nitta K, Shinohara Y, Konno A, Hirai H.
Development of microglia-targeting adeno-associated viral vectors as tools to study microglial behavior in vivo.
Commun Biol. 2022 Nov 11;5(1):1224. doi: 10.1038/s42003-022-04200-3.
Ninomiya A, Amano I, Kokubo M, Takatsuru Y, Ishii S, Hirai H, Hosoi N, Koibuchi N.
Long-term depression-inductive stimulation causes long-term potentiation in mouse Purkinje cells with a mutant thyroid hormone receptor.
Proc Natl Acad Sci USA. 2022 Nov 8;119(45):e2210645119. doi: 10.1073/pnas.2210645119. Epub 2022 Nov 2.
Morizawa YM, Matsumoto M, Nakashima Y, Endo N, Aida T, Ishikane H, Beppu K, Moritoh S, Inada H, Osumi N, Shigetomi E, Koizumi S, Yang G, Hirai H, Tanaka K, Tanaka KF, Ohno N, Fukazawa Y, Matsui K.
Synaptic pruning through glial synapse engulfment upon motor learning.
Nat Neurosci. 2022 Nov;25(11):1458-1469. doi: 10.1038/s41593-022-01184-5. Epub 2022 Nov 1.
Wang X, Delle C, Asiminas A, Akther S, Vittani M, Brøgger P, Kusk P, Vo CT, Radovanovic T, Konno A, Hirai H, Fukuda M, Weikop P, Goldman SA, Nedergaard M, Hirase H.
Liver-secreted fluorescent blood plasma markers enable chronic imaging of the microcirculation.
Cell Rep Methods. 2022 Sep 21;2(10):100302. doi: 10.1016/j.crmeth.2022.100302. eCollection 2022 Oct 24.
Shuvaev AN, Belozor OS, Mozhei OI, Shuvaev AN, Fritsler YV, Khilazheva ED, Mosyagina AI, Hirai H, Teschemacher AG, Kasparov S.
Indirect Negative Effect of Mutant Ataxin-1 on Short- and Long-Term Synaptic Plasticity in Mouse Models of Spinocerebellar Ataxia Type 1.
Cells. 2022 Jul 20;11(14):2247. doi:10.3390/cells11142247
Tokuyama T, Uosaki H, Sugiura A, Nishitai G, Takeda K, Nagashima S, Shiiba I, Ito N, Amo T, Mohri S, Nishimura A, Nishida M, Konno A, Hirai H, Ishido S, Yoshizawa T, Shindo T, Takada S, Kinugawa S, Inatome R, Yanagi S
Protective roles of MITOL against myocardial senescence and ischemic injury partly via Drp1 regulation.
iScience. 2022 Jun 11;25(7):104582. doi: 10.1016/j.isci.2022.104582.
Inada K, Hagihara M, Tsujimoto K, Abe T, Konno A, Hirai H, Kiyonari H, Miyamichi K.
Plasticity of neural connections underlying oxytocin-mediated parental behaviors of male mice.
Neuron. 2022 Jun 15;110(12):2009-2023.e5. doi: 10.1016/j.neuron.2022.03.033. Epub 2022 Apr 19.
Ueda E, Ohta T, Konno A, Hirai H, Kurauchi Y, Katsuki H, Seki T.
D-Cysteine Activates Chaperone-Mediated Autophagy in Cerebellar Purkinje Cells via the Generation of Hydrogen Sulfide and Nrf2 Activation.
Cells. 2022 Apr 5;11(7):1230. doi: 10.3390/cells11071230.
Hirai H, Fukai Y, Konno A, Hosoi N.
Electrophysiological and Imaging Analysis of GFP-Tagged Protein Kinase C γ Translocation in Cerebellar Purkinje Cells.
Cerebellum. 2022 Oct;21(5):776-783. doi: 10.1007/s12311-022-01384-6. Epub 2022 Feb 26.
Sakai A, Yasui T, Watanave M, Tatsumi R, Yamamoto Y, Takano W, Tani Y, Okamura I, Hirai H, Takeda S.
Development of novel potent ligands for GPR85, an orphan G protein-coupled receptor expressed in the brain.
Genes Cells. 2022 May;27(5):345-355. doi: 10.1111/gtc.12931. Epub 2022 Mar 1.
Watanave M, Takahashi N, Hosoi N, Konno A, Yamamoto H, Yasui H, Kawachi M, Horii T, Matsuzaki Y, Hatada I, Hirai H.
Protein kinase Cγ in cerebellar Purkinje cells regulates Ca 2+-activated large-conductance K + channels and motor coordination
Proc Natl Acad Sci U S A. 2022 Feb 15;119(7):e2113336119. doi: 10.1073/pnas.2113336119.
Suzuki A, Kosugi S, Murayama E, Sasakawa E, Ohkawa N, Konno A, Hirai H, Inokuchi K.
A cortical cell ensemble in the posterior parietal cortex controls past experience-dependent memory updating.
Nat Commun. 2022 Jan 11;13(1):41. doi: 10.1038/s41467-021-27763-x
Ninomiya A, Mshaty A, Haijima A, Yajima H, Kokubo M, Khairinisa MA, Ariyani W, Fujiwara Y, Ishii S, Hosoi N, Hirai H, Amano I, Koibuchi N.
The neurotoxic effect of lactational PFOS exposure on cerebellar functional development in male mice.
Food Chem Toxicol. 2022 Jan;159:112751. doi: 10.1016/j.fct.2021.112751. Epub 2021 Dec 3.
2021年
- Cendelin J, Cvetanovic M, Gandelman M, Hirai H, Orr HT, Pulst SM, Strupp M, Tichanek F, Tuma J, Manto M.
Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications.
Cerebellum. 2021 Aug 10. doi: 10.1007/s12311-021-01311-1. Online ahead of print. - Kawakami R, Matsui M, Konno A, Kaneko R, Shrestha S, Shrestha S, Sunaga H, Hanaoka H, Goto S, Hosojima M, Kabasawa H, Obokata M, Koitabashi N, Matsui H, Sasaki T, Saito A, Yanagita M, Hirai H, Kurabayashi M, Iso T.
Urinary FABP1 is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury.
J Pathol. 2021 Dec;255(4):362-373. doi: 10.1002/path.5775. Epub 2021 Sep 1. - Ohta T, Morikawa Y, Sato M, Konno A, Hirai H, Kurauchi Y, Hisatsune A, Katsuki H, Seki T.
Therapeutic potential of d-cysteine against in vitro and in vivo models of spinocerebellar ataxia.
Exp Neurol. 2021 Sep;343:113791. doi: 10.1016/j.expneurol.2021.113791. Epub 2021 Jun 19. - Radhiyanti PT, Konno A, Matsuzaki Y, Hirai H.
Comparative study of neuron-specific promoters in mouse brain transduced by intravenously administered AAV-PHP.eB.
Neurosci Lett. 2021 Jun 21;756:135956. doi: 10.1016/j.neulet.2021.135956. Epub 2021 May 11. - Nagao S, Hirai H, Kano M, Yuzaki M.
Masao Ito-A Visionary Neuroscientist with a Passion for the Cerebellum.
Neuroscience. 2021 May 10;462:1-3. doi: 10.1016/j.neuroscience.2021.02.028. - Shuvaev AN, Belozor OS, Mozhei O, Yakovleva DA, Potapenko IV, Shuvaev AN, Smolnikova MV, Salmin VV, Salmina AB, Hirai H, Teschemacher AG, Kasparov S.
Chronic optogenetic stimulation of Bergman glia leads to dysfunction of EAAT1 and Purkinje cell death, mimicking the events caused by expression of pathogenic ataxin-1.
Neurobiol Dis. 2021 Jul;154:105340. doi: 10.1016/j.nbd.2021.105340. Epub 2021 Mar 19. - Sugimoto H, Horii T, Hirota JN, Sano Y, Shinoda Y, Konno A, Hirai H, Ishizaki Y, Hirase H, Hatada I, Furuichi T, Sadakata T.
The Ser19Stop single nucleotide polymorphism (SNP) of human PHYHIPL affects the cerebellum in mice.
Mol Brain. 2021 Mar 12;14(1):52. doi: 10.1186/s13041-021-00766-x. - Hoshino C, Konno A, Hosoi N, Kaneko R, Mukai R, Nakai J, Hirai H.
GABAergic neuron-specific whole-brain transduction by AAV-PHP.B incorporated with a new GAD65 promoter.
Mol Brain. 2021 Feb 15;14(1):33. doi: 10.1186/s13041-021-00746-1. - Ohgami N, Iizuka A, Hirai H, Yajima I, Iida M, Shimada A, Tsuzuki T, Jijiwa M, Asai N, Takahashi M, Kato M.
Loss-of-function mutation of c-Ret causes cerebellar hypoplasia in mice with Hirschsprung disease and Down’s syndrome.
J Biol Chem. Jan-Jun 2021;296:100389. doi: 10.1016/j.jbc.2021.100389. Epub 2021 Feb 6.
2020年
- Inoue A, Kobayashi T, Hirai H, Kanaya N, Kohara K.
Protocol for BATTLE-1EX: A High-Resolution Imaging Method to Visualize Whole Synaptic Structures and their Components in the Nervous System.
J STAR Protoc. 2020 Nov 25;1(3):100166. doi: 10.1016/j.xpro.2020.100166. eCollection 2020 Dec 18. - Konno A, Hirai H.
Efficient whole brain transduction by systemic infusion of minimally purified AAV-PHP.eB.
J Neurosci Methods. 2020 Aug 15;346:108914. doi: 10.1016/j.jneumeth.2020.108914. - Sato M, Ohta T, Morikawa Y, Konno A, Hirai H, Kurauchi Y, Hisatsune A, Katsuki H, Seki T.
Ataxic phenotype and neurodegeneration are triggered by the impairment of chaperone-mediated autophagy in cerebellar neurons.
Neuropathol Appl Neurobiol. 2020 Jul 28. doi: 10.1111/nan.12649. - Sato M, Ueda E, Konno A, Hirai H, Kurauchi Y, Hisatsune A, Katsuki H, Seki T.
Glucocorticoids negatively regulates chaperone mediated autophagy and microautophagy.
Biochem Biophys Res Commun. 2020 Jul 12;528(1):199-205. doi: 10.1016/j.bbrc.2020.04.132. - Kohara K, Inoue A, Nakano Y, Hirai H, Kobayashi T, Maruyama M, Baba R, Kawashima C.
BATTLE: Genetically Engineered Strategies for Split-Tunable Allocation of Multiple Transgenes in the Nervous System.
iScience. 2020 Jun 26;23(6):101248. doi: 10.1016/j.isci.2020.101248 - Chao OY, Marron Fernandez de Velasco E, Pathak SS, Maitra S, Zhang H, Duvick L, Wickman K, Orr HT, Hirai H, Yang YM.
Targeting Inhibitory Cerebellar Circuitry to Alleviate Behavioral Deficits in a Mouse Model for Studying Idiopathic Autism.
Neuropsychopharmacology. 2020 Mar 16. doi: 10.1038/s41386-020-0656-5. - Yasui H, Matsuzaki Y, Konno A, Hirai H.
Global knockdown of retinoid-related orphan receptor α in mature Purkinje cells reveals aberrant cerebellar phenotypes of spinocerebellar ataxia.
Neuroscience. 2020 Apr. doi: 10.1016/j.neuroscience.2020.04.004. - Oe Y, Wang X, Patriarchi T, Konno A, Ozawa K, Yahagi K, Hirai H, Tsuboi T, Kitaguchi T, Tian L, McHugh TJ, Hirase H.
Distinct temporal integration of noradrenaline signaling by astrocytic second messengers during vigilance.
Nature Communications. 2020 Jan 24;11(1):471. doi: 10.1038/s41467-020-14378-x.
2019年
- Matsumoto K, Mitani TT, Horiguchi SA, Kaneshiro J, Murakami TC, Mano T, Fujishima H, Konno A, Watanabe TM, Hirai H, Ueda HR.
Advanced CUBIC tissue clearing for whole-organ cell profiling.
Nature Protocols, 2019 Dec;14(12):3506-3537.
ウイルスベクター開発研究センター発足前の成果
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アストロサイト特異的AAVベクター
Shinohara Y, Konno A, Takahashi N, Matsuzaki Y, Kishi S, Hirai H.
Viral Vector-Based Dissection of Marmoset GFAP Promoter in Mouse and Marmoset Brains.
PLoS One. 2016 Aug 29;11(8):e0162023. -
ニューロン特異的AAVベクター
Shinohara Y, Ohtani T, Konno A, Hirai H
Viral Vector-Based Evaluation of Regulatory Regions in the Neuron-Specific Enolase (NSE) Promoter in Mouse Cerebellum In Vivo.
Cerebellum. 2017 Dec;16(5-6):913-922. -
プルキンエ細胞特異的AAVベクター
Nitta K, Matsuzaki Y, Konno A, Hirai H
Minimal Purkinje Cell-Specific PCP2/L7 Promoter Virally Available for Rodents and Non-human Primates.
Mol Ther Methods Clin Dev. 2017 Jul 27;6:159-170. -
AAVカプシドに対する中和抗体産生
Shinohara Y, Konno A, Nitta K, Matsuzaki Y, Yasui H, Suwa J, Hiromura K, Hirai H.
Effects of Neutralizing Antibody Production on AAV-PHP.B-Mediated Transduction of the Mouse Central Nervous System.
Mol Neurobiol. 2019 Jun;56(6):4203-4214. -
マーモセット中枢神経系への遺伝子発現
Matsuzaki Y, Konno A, Mochizuki R, Shinohara Y, Nitta K, Okada Y, Hirai H
Intravenous administration of the adeno-associated virus-PHP.B capsid fails to upregulate transduction efficiency in the marmoset brain.
Neurosci Lett. 2018 Feb 5;665:182-188.
Matsuzaki Y, Konno A, Mukai R, Honda F, Hirato M, Yoshimoto Y, Hirai H.
Transduction Profile of the Marmoset Central Nervous System Using Adeno-Associated Virus Serotype 9 Vectors.
Mol Neurobiol. 2017 Apr;54(3):1745-1758. -
血液脳関門透過型AAVベクター
Matsuzaki Y, Tanaka M, Hakoda S, Masuda T, Miyata R, Konno A, Hirai H
Neurotropic Properties of AAV-PHP.B Are Shared among Diverse Inbred Strains of Mice.
Mol Ther. 2019 Apr 10;27(4):700-704. Epub 2019 Feb 28.