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イタノ ナオキ
ITANO NAOKI
板野 直樹 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2014/04 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Hyaluronan Deficiency Due to Has3 Knock-Out Causes Altered Neuronal Activity and Seizures via Reduction in Brain Extracellular Space |
| 執筆形態 | その他 |
| 掲載誌名 | JOURNAL OF NEUROSCIENCE |
| 出版社・発行元 | SOC NEUROSCIENCE |
| 巻・号・頁 | 34(18),pp.6164-6176 |
| 著者・共著者 | Amaia M. Arranz,Katherine L. Perkins,Fumitoshi Irie,David P. Lewis,Jan Hrabe,Fanrong Xiao,Naoki Itano,Koji Kimata,Sabina Hrabetova,Yu Yamaguchi |
| 概要 | Hyaluronan (HA), a large anionic polysaccharide (glycosaminoglycan), is a major constituent of the extracellular matrix of the adult brain. To address its function, we examined the neurophysiology of knock-out mice deficient in hyaluronan synthase (Has) genes. Here we report that these Has mutant mice are prone to epileptic seizures, and that in Has3(-/-) mice, this phenotype is likely derived from a reduction in the size of the brain extracellular space (ECS). Among the three Has knock-out models, namely Has3(-/-), Has1(-/-), and Has2(CKO), the seizures were most prevalent in Has3(-/-) mice, which also showed the greatest HA reduction in the hippocampus. Electrophysiology in Has3(-/-) brain slices demonstrated spontaneous epileptiform activity in CA1 pyramidal neurons, while histological analysis revealed an increase in cell packing in the CA1 stratum pyramidale. Imaging of the diffusion of a fluorescent marker revealed that the transit of molecules through the ECS of this layer was reduced. Quantitative analysis of ECS by the real-time iontophoretic method demonstrated that ECS volume was selectively reduced in the stratum pyramidale by similar to 40% in Has3(-/-) mice. Finally, osmotic manipulation experiments in brain slices from Has3(-/-) and wild-type mice provided evidence for a causal link between ECS volume and epileptiform activity. Our results provide the first direct evidence for the physiological role of HA in the regulation of ECS volume, and suggest that HA-based preservation of ECS volume may offer a novel avenue for development of antiepileptogenic treatments. |
| DOI | 10.1523/JNEUROSCI.3458-13.2014 |
| ISSN | 0270-6474 |