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-
HUMAN GENE THERAPY 28(12) A4-A4 2017年12月
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JOURNAL OF NEUROTRAUMA 34(13) A142-A143 2017年7月
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JOURNAL OF NEUROTRAUMA 34(13) A158-A158 2017年7月
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MOLECULAR THERAPY 25(5) 139-139 2017年5月
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MOLECULAR THERAPY 25(5) 105-105 2017年5月
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MOLECULAR THERAPY 25(5) 108-108 2017年5月
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MOLECULAR THERAPY 25(5) 246-246 2017年5月
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JOURNAL OF PHYSIOLOGICAL SCIENCES 67(1) 11-17 2017年1月We overview the 16-kDa proteolipid mediatophore, the transmembrane c-subunit of the V0 sector of the vacuolar proton ATPase (ATP6V0C) that was shown to mediate the secretion of acetylcholine. Acetylcholine, serotonin, and dopamine (DA) are released from cell soma and/or dendrites if ATP6V0C is expressed in cultured cells. Adeno-associated viral vector-mediated gene transfer of ATP6V0C into the caudate putamen enhanced the depolarization-induced overflow of endogenous DA in Parkinson-model mice. Motor impairment was ameliorated in hemiparkinsonian model mice when ATP6V0C was expressed with DA-synthesizing enzymes. The review discusses application in the future as a potential tool for gene therapy, cell transplantation therapy, and inducible pluripotent stem cell therapy in neurological diseases, from the view point of recent findings regarding vacuolar ATPase.
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HUMAN GENE THERAPY 27(11) A146-A147 2016年11月
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HUMAN GENE THERAPY 27(11) A45-A45 2016年11月
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INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 19 88-88 2016年6月
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INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 19 226-226 2016年6月
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INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 19 161-161 2016年6月
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日本アルコール・薬物医学会雑誌 50(4) 206-206 2015年8月
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JOURNAL OF PHARMACOLOGICAL SCIENCES 128(3) S188-S188 2015年7月
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An Update on Gene Therapy for the Treatment of Aromatic L-Amino Acid Decarboxylase (AADC) DeficiencyMOLECULAR THERAPY 23 S103-S103 2015年5月
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MOLECULAR THERAPY 23 S80-S80 2015年5月
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ビタミン 89(4) 248-248 2015年4月25日
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成人病と生活習慣病 : 日本成人病(生活習慣病)学会準機関誌 45(2) 213-217 2015年2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