Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice.
Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice.
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DOI：
10.1038/s41467-023-39941-0
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发表时间：
2023-08-10
影响因子：
16.6
通讯作者：
Picard, Martin
中科院分区：
文献类型：
--
作者：
Rosenberg, Ayelet M.;Saggar, Manish;Monzel, Anna S.;Devine, Jack;Rogu, Peter;Limoges, Aaron;Junker, Alex;Sandi, Carmen;Mosharov, Eugene V.;Dumitriu, Dani;Anacker, Christoph;Picard, Martin
大脑和行为受到能量的约束，受到线粒体能量转换能力的限制。然而，大脑行为的关系还没有在全脑范围内进行系统的研究。在这里，我们研究了线粒体呼吸链容量的多个特征和应激相关行为的雄性小鼠不同的行为表型之间的关联。对17个脑区的571个样本进行了线粒体呼吸链酶活性和线粒体DNA（mtDNA）含量的小型化测定，定义了线粒体行为关联的特定模式。通过将多切片网络分析应用于我们的全脑线粒体数据集，我们确定了三个具有共享线粒体特征的大规模脑区网络。由皮质-纹状体区组成的主要网络表现出最强的神经行为相关性，占动物间行为差异的50%，这表明这种基于线粒体的网络在功能上是重要的。基于线粒体的脑网络也与区域基因表达和结构连接重叠，并表现出不同的分子线粒体表型特征。这项工作提供了融合的多模态证据，锚定在酶活性，基因表达和动物行为，不同的，行为相关的线粒体表型存在于整个雄性小鼠大脑。脑线粒体在影响认知方面发挥着至关重要的作用，但它们的多样性往往被忽视。这项对小鼠的研究确定了不同的线粒体表型，这些表型分布为大规模网络，占动物间行为变异的很大一部分。
The brain and behavior are under energetic constraints, limited by mitochondrial energy transformation capacity. However, the mitochondria-behavior relationship has not been systematically studied at a brain-wide scale. Here we examined the association between multiple features of mitochondrial respiratory chain capacity and stress-related behaviors in male mice with diverse behavioral phenotypes. Miniaturized assays of mitochondrial respiratory chain enzyme activities and mitochondrial DNA (mtDNA) content were deployed on 571 samples across 17 brain areas, defining specific patterns of mito-behavior associations. By applying multi-slice network analysis to our brain-wide mitochondrial dataset, we identified three large-scale networks of brain areas with shared mitochondrial signatures. A major network composed of cortico-striatal areas exhibited the strongest mitochondria-behavior correlations, accounting for up to 50% of animal-to-animal behavioral differences, suggesting that this mito-based network is functionally significant. The mito-based brain networks also overlapped with regional gene expression and structural connectivity, and exhibited distinct molecular mitochondrial phenotype signatures. This work provides convergent multimodal evidence anchored in enzyme activities, gene expression, and animal behavior that distinct, behaviorally-relevant mitochondrial phenotypes exist across the male mouse brain. Brain mitochondria play crucial roles that influence cognition, yet their diversity is often overlooked. This study in mice identifies distinct mitochondrial phenotypes distributed as large-scale networks, accounting for a large portion of animal-to-animal behavioural variation.
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上皮卵巢癌中的线粒体表现出异常的表型和与生物行为因子的钝化关联。
影响因子：
4.6
作者：
Bindra S;McGill MA;Triplett MK;Tyagi A;Thaker PH;Dahmoush L;Goodheart MJ;Ogden RT;Owusu-Ansah E;R Karan K;Cole S;Sood AK;Lutgendorf SK;Picard M
通讯作者：
Picard M
影响因子：
8.8
作者：
Faitg J;Lacefield C;Davey T;White K;Laws R;Kosmidis S;Reeve AK;Kandel ER;Vincent AE;Picard M
通讯作者：
Picard M
影响因子：
5.3
作者：
Fanet H;Capuron L;Castanon N;Calon F;Vancassel S
通讯作者：
Vancassel S
DOI：
10.1073/pnas.1018985108
发表时间：
2011-05-03
影响因子：
11.1
作者：
Bassett, Danielle S.;Wymbs, Nicholas F.;Grafton, Scott T.
通讯作者：
Grafton, Scott T.
影响因子：
25
作者：
Bassett DS;Yang M;Wymbs NF;Grafton ST
通讯作者：
Grafton ST