Regulatory mechanisms of brain function by alternative splicing products of fosB gene

fosB基因选择性剪接产物对脑功能的调节机制

• 批准号: 23657116
• 负责人: NAKABEPPU Yusaku
• 金额: $ 2.5万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23657116/
• 关键词: 転写; 選択的スプライシング; 成体脳神経新生; てんかん; うつ; 最初期遺伝子; 側頭葉てんかん; うつ病; 海馬硬化; 遺伝子発現プロファイリング; AP-1転写因子; 前初期遺伝子

Under various brain stress, expression of fosB gene which encodes subunits of AP-1 transcription factor is highly induced in the hippocampus of mouse brain. The fosB gene produces two mature mRNAs (fosB and ・fosB) by alternative splicing, and whose products differentially regulate the response to various brain stress. Our analyses of fosB-null mice and mutant mice which produce only one of the two mRNAs revealed that both of the two fosB mRNA products play distinct roles in control of the adult neurogenesis in hippocampal dentate gyrus through regulating expression of various genes, and thus suppressing epilepsy and depressive behavior.

在各种脑应激下，编码AP-1转录因子亚基的fosB基因在小鼠大脑海马中高度诱导表达。fosB基因通过选择性剪接产生两种成熟mRNA（fosB和·fosB），其产物具有差异性调节。我们对 fosB 缺失小鼠和仅产生两种 mRNA 之一的突变小鼠的分析表明，这两种 fosB mRNA 产物在控制成年小鼠中发挥着不同的作用。通过调节各种基因的表达来调节海马齿状回的神经发生，从而抑制癫痫和抑郁行为。

项目成果

fosB-Null Mice Display Impaired Adult Hlppocampal Neurogenesis and Spontaneous Epilepsy

fosB 缺失小鼠表现出成年海马神经发生受损和自发性癫痫

• DOI: 10.1038/npp.2012.260
• 发表时间: 2013
• 期刊: Neuropsychopharmacology
• 影响因子: 7.6
• 作者: Yutsudo;N;et. al.
• 通讯作者: et. al.

脳内細胞におけるfosBによる遺伝子プロファイルの網羅的解析

脑细胞fosB基因谱综合分析

• 发表时间: 2011
• 作者: 能丸寛子;大西克典;外間政朗;湯通堂紀子;中別府雄作
• 通讯作者: 中別府雄作

ΔFosB and/or Δ2ΔFosB regulate proliferation of adult hippocampal neural progenitor cells and suppress spontaneous epileptic seizures

ΔFosB和/或Δ2ΔFosB调节成人海马神经祖细胞的增殖并抑制自发性癫痫发作

• 发表时间: 2011
• 作者: Noriko Yutsudo;Takashi Kamada;Hiroko Nomaru;Yoko H.Ohnishi;Yoshinori N.Ohnishi;Kosuke Kajitani;Kunihiko Sakumi;Hiroshi Shigeto;Yusaku Nakabeppu
• 通讯作者: Yusaku Nakabeppu

Comprehensive analysis of gene expression regulated by fosB gene in neuron and glia

fosB基因在神经元和胶质细胞中调控基因表达的综合分析

• 发表时间: 2012
• 作者: H.Nomaru;N.Yutsudo;M.Hokoma;Y.Nakabeppu
• 通讯作者: Y.Nakabeppu

FosB is essential for the enhancement of stress tolerance and antagonizes locomotor sensitization by ΔFosB.

• DOI: 10.1016/j.biopsych.2011.04.021
• 发表时间: 2011-09-01
• 期刊: BIOLOGICAL PSYCHIATRY
• 影响因子: 10.6
• 作者: Ohnishi, Yoshinori N.;Ohnishi, Yoko H.;Hokama, Masaaki;Nomaru, Hiroko;Yamazaki, Katsuhisa;Tominaga, Yohei;Sakumi, Kunihiko;Nestler, Eric J.;Nakabeppu, Yusaku
• 通讯作者: Nakabeppu, Yusaku