基本情報
- 所属
- 自治医科大学 医学部 客員教授
- 学位
- 医学博士(自治医科大学)
- ORCID ID
https://orcid.org/0000-0002-3185-7790
- J-GLOBAL ID
- 200901074911542236
- researchmap会員ID
- 1000063389
神経疾患の遺伝子治療を開発しています。
研究キーワード
14経歴
6-
2024年4月 - 現在
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2008年11月 - 現在
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2019年4月 - 2024年3月
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2019年4月 - 2024年3月
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2014年11月 - 2019年3月
委員歴
2-
- 現在
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- 2019年5月
受賞
4-
2019年3月
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2011年7月
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2009年6月
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2000年6月
論文
366-
Nature Communications 2024年6月 査読有り
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International journal of cardiology 400 131704-131704 2024年4月1日
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Biological & pharmaceutical bulletin 2024年3月1日Diabetic retinopathy (DR) can cause visual impairment and blindness, and the increasing global prevalence of diabetes underscores the need for effective therapies to prevent and treat DR. Therefore, this study aimed to evaluate the protective effect of pemafibrate treatment against DR, using a Spontaneously Diabetic Torii (SDT) fatty rat model of obese type 2 diabetes. SDT fatty rats were fed either a diet supplemented with pemafibrate (0.3 mg/kg/day) for 16 weeks, starting at 8 weeks of age (Pf SDT fatty: study group), or normal chow (SDT fatty: controls). Normal chow was provided to Sprague-Dawley (SD) rats (SD: normal controls). Electroretinography (ERG) was performed at 8 and 24 weeks of age to evaluate the retinal neural function. After sacrifice, retinal thickness, number of retinal folds, and choroidal thickness were evaluated, and immunostaining was performed for aquaporin-4 (AQP4). No significant differences were noted in food consumption, body weight, or blood glucose level after pemafibrate administration. Triglyceride levels were reduced, and high-density lipoprotein cholesterol levels were increased. Extension of oscillatory potential (OP)1 and OP3 waves on ERG was suppressed in the Pf SDT fatty group. Retinal thickness at 1,500 microns from the optic disc improved in the Pf SDT fatty group. No significant improvements were noted in choroidal thickness or number of retinal folds. Quantitative analyses showed that AQP4-positive regions in the retinas were significantly larger in the Pf SDT fatty group than in the SDT fatty group. The findings suggest that pemafibrate treatment can exert protective effects against DR.
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eNeuro 10(10) 2023年10月Depression is a frequent and serious illness, and stress is considered the main risk factor for its onset. First-line antidepressants increase serotonin (5-hydroxytryptamine; 5-HT) levels in the brain. We previously reported that an N-acetyltransferase, Shati/Nat8l, is upregulated in the dorsal striatum (dSTR) of stress-susceptible mice exposed to repeated social defeat stress (RSDS) and that dSTR Shati/Nat8l overexpression in mice (dSTR-Shati OE) induces stress vulnerability and local reduction in 5-HT content. Male mice were used in this study, and we found that dSTR 5-HT content decreased in stress-susceptible but not in resilient mice. Moreover, vulnerability to stress in dSTR-Shati OE mice was suppressed by the activation of serotonergic neurons projecting from the dorsal raphe nucleus (dRN) to the dSTR, followed by upregulation of 5-HT content in the dSTR using designer receptors exclusively activated by designer drugs (DREADD). We evaluated the role of GABA in modulating the serotonergic system in the dRN. Stress-susceptible after RSDS and dSTR-Shati OE mice exhibited an increase in dRN GABA content. Furthermore, dRN GABA content was correlated with stress sensitivity. We found that the blockade of GABA signaling in the dRN suppressed stress susceptibility in dSTR-Shati OE mice. In conclusion, we propose that dSTR 5-HT and dRN GABA, controlled by striatal Shati/Nat8l via the dSTR-dRN neuronal circuitry, critically regulate stress sensitivity. Our study provides insights into the neural processes that underlie stress and suggests that dSTR Shati/Nat8l could be a novel therapeutic target for drugs against depression, allowing direct control of the dRN serotonergic system.
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Human gene therapy 34(19-20) 1064-1071 2023年10月The inner ear is a primary lesion in sensorineural hearing loss and has been a target in gene therapy. The efficacy of gene therapy depends on achieving sufficient levels of transduction at a safe vector dose. Vectors derived from various adeno-associated viruses (AAVs) are predominantly used to deliver therapeutic genes to inner ear cells. AAV9 and its variants vector are attractive candidates for clinical applications since they can cross the mesothelial cell layer and transduce inner hair cells (IHCs), although this requires relatively high doses. In this study, we investigated the effects of sucrose on the transduction of a variant of the AAV9 vector for gene transfer in the inner ear. We found that high concentrations of sucrose increased gene transduction in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in vitro. In addition, we demonstrated that simultaneous administration of sucrose enhanced the transduction of mouse IHCs and spiral ligament cells using an AAV9 variant vector. The procedure did not increase the thresholds in the auditory brainstem response, suggesting that sucrose had no adverse effect on auditory function. This versatile method may be valuable in the development of novel gene therapies for adult-onset sensorineural hearing loss.
MISC
214-
NEUROSCIENCE RESEARCH 71 E140-E141 2011年
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NEUROSCIENCE RESEARCH 71 E101-E101 2011年
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NEUROSCIENCE RESEARCH 71 E213-E214 2011年
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乱用薬物による薬物依存の発症メカニズム・予防・診断及び治療法に関する研究 平成22年度 総括研究報告書 45-54 2011年
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運動失調症の病態解明と治療法開発に関する研究班 平成22年度 総括・分担研究報告書 17-19 2011年
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JOURNAL OF GENE MEDICINE 12(12) 1024-1024 2010年12月
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NEUROSCIENCE RESEARCH 68 E66-E66 2010年
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NEUROSCIENCE RESEARCH 68 E55-E56 2010年
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Functional neurosurgery : proceedings of the annual meeting of the Japan Society for Stereotactic and Functional Neurosurgery 48(2) 128-132 2009年12月12日
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JOURNAL OF GENE MEDICINE 11(12) 1151-1152 2009年12月
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日本臨床 67 444-447 2009年6月
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日本臨床 67 448-451 2009年6月
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MOLECULAR THERAPY 17 S168-S168 2009年5月
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NEUROSCIENCE RESEARCH 65 S24-S24 2009年
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JOURNAL OF PHYSIOLOGICAL SCIENCES 59 170-170 2009年
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日本東洋醫學雜誌 59 172-172 2008年5月7日
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日本東洋醫學雜誌 59 205-205 2008年5月7日
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JOURNAL OF PHARMACOLOGICAL SCIENCES 106 138P-138P 2008年
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日本組織細胞化学会総会プログラムおよび抄録集 (48) 122-122 2007年9月28日
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NEUROSCIENCE RESEARCH 58 S138-S138 2007年
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Functional neurosurgery : proceedings of the annual meeting of the Japan Society for Stereotactic and Functional Neurosurgery 45(2) 148-152 2006年12月10日
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JOURNAL OF GENE MEDICINE 8(12) 1469-1469 2006年12月
共同研究・競争的資金等の研究課題
17-
日本学術振興会 科学研究費助成事業 2022年6月 - 2025年3月
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日本学術振興会 科学研究費助成事業 2020年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 2016年4月 - 2018年3月
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日本学術振興会 科学研究費助成事業 2015年4月 - 2018年3月
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日本学術振興会 科学研究費助成事業 2015年4月 - 2017年3月