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イシヅカ ユウタ
Yuta Ishizuka
石塚 佑太 所属 川崎医科大学 医学部 基礎医学 病態代謝学 職種 講師 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Drebrin A regulates hippocampal LTP and hippocampus-dependent fear learning in adult mice. |
| 掲載誌名 | 正式名：Neuroscience 略 称：Neuroscience ISSNコード：18737544/03064522 |
| 掲載区分 | 国外 |
| 出版社 | ELSEVIER |
| 巻・号・頁 | 324,pp.218-26 |
| 著者・共著者 | Nobuhiko Kojima, Hiroki Yasuda, Kenji Hanamura, Yuta Ishizuka, Yuko Sekino, Tomoaki Shirao |
| 発行年月 | 2016/06 |
| 概要 | Structural plasticity of dendritic spines, which underlies higher brain functions including learning and memory, is dynamically regulated by the actin cytoskeleton and its associated proteins. Drebrin A is an F-actin-binding protein preferentially expressed in the brain and localized in the dendritic spines of mature neurons. Isoform conversion from drebrin E to drebrin A and accumulation of the latter in dendritic spines occurs during synapse maturation. We have previously demonstrated that drebrin A plays a pivotal role in spine morphogenesis and plasticity. However, it is unclear whether drebrin A plays a specific role in processes required for structural plasticity, and whether drebrin E can substitute in this role. To answer these questions, we analyzed mutant mice (named DAKO mice), in which isoform conversion from drebrin E to drebrin A is disrupted. In DAKO mouse brain, drebrin E continues to be expressed throughout life instead of drebrin A. Electrophysiological studies using hippocampal slices revealed that long-term potentiation of CA1 synapses was impaired in adult DAKO mice, but not in adolescents. In parallel with this age-dependent impairment, DAKO mice exhibited impaired hippocampus-dependent fear learning in an age-dependent manner; the impairment was evident in adult mice, but not in adolescents. In addition, histological investigation revealed that the spine length of the apical dendrite of CA1 pyramidal cells was significantly longer in adult DAKO mice than in wild-type mice. Our data indicate that the roles of drebrin E and drebrin A in brain function are different from each other, that the isoform conversion of drebrin is critical, and that drebrin A is indispensable for normal synaptic plasticity and hippocampus-dependent fear memory in the adult brain. |
| DOI | 10.1016/j.neuroscience.2016.03.015 |
| PMID | 26970584 |