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发育过程中抑制线粒体钙单向转运体损害成年果蝇的记忆。

Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs Memory in Adult Drosophila.

作者信息

Drago Ilaria, Davis Ronald L

机构信息

Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.

Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.

出版信息

Cell Rep. 2016 Sep 6;16(10):2763-2776. doi: 10.1016/j.celrep.2016.08.017. Epub 2016 Aug 25.

Abstract

The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn)-a brain region critical for olfactory memory formation-causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism.

摘要

细胞质钙摄入线粒体对于多种生理过程至关重要,包括钙缓冲、新陈代谢和细胞存活。在此,我们证明,在果蝇蘑菇体神经元(MBn)——对嗅觉记忆形成至关重要的脑区——中抑制线粒体钙单向转运体,会导致记忆受损,而不会改变学习能力。仅在化蛹期间抑制单向转运体活性会损害成年果蝇的记忆,而在成年期进行同样的抑制则没有效果。行为障碍与MBn的结构缺陷有关,包括突触小泡减少和αβ MBn轴突长度增加。我们的结果揭示了线粒体单向转运体复合物在成年生物体中为正常记忆形成建立必要的结构和功能神经元底物方面的体内发育作用。

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本文引用的文献

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Architecture of the mitochondrial calcium uniporter.线粒体钙单向转运体的结构
Nature. 2016 May 12;533(7602):269-73. doi: 10.1038/nature17656. Epub 2016 May 2.
2
Homozygous deletion in MICU1 presenting with fatigue and lethargy in childhood.MICU1 纯合缺失导致儿童期出现疲劳和嗜睡。
Neurol Genet. 2016 Mar 3;2(2):e59. doi: 10.1212/NXG.0000000000000059. eCollection 2016 Apr.
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The molecular era of the mitochondrial calcium uniporter.线粒体钙离子单向转运体的分子时代。
Nat Rev Mol Cell Biol. 2015 Sep;16(9):545-53. doi: 10.1038/nrm4039. Epub 2015 Aug 19.
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Functional neuroanatomy of Drosophila olfactory memory formation.果蝇嗅觉记忆形成的功能神经解剖学
Learn Mem. 2014 Sep 15;21(10):519-26. doi: 10.1101/lm.034363.114. Print 2014 Oct.
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Unresolved questions from the analysis of mice lacking MCU expression.缺乏 MCU 表达的小鼠分析中的未解决问题。
Biochem Biophys Res Commun. 2014 Jul 11;449(4):384-5. doi: 10.1016/j.bbrc.2014.04.144. Epub 2014 May 1.

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