Socially responsive effects of brain oxidative metabolism on aggression
Socially responsive effects of brain oxidative metabolism on aggression
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DOI：
10.1073/pnas.1412306111
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发表时间：
2014-08-26
影响因子：
11.1
通讯作者：
Robinson, Gene E.
中科院分区：
文献类型：
--
作者：
Li-Byarlay, Hongmei;Rittschof, Clare C.;Robinson, Gene E.
尽管持续存在高能量需求，大脑并不总是以通过氧化磷酸化产生最大 ATP 的比例使用葡萄糖和氧气。在某些情况下，尽管有足够的氧气供应，葡萄糖消耗量仍超过氧气消耗量，这种现象称为有氧糖酵解。尽管代谢可塑性似乎对正常认知至关重要，但研究其功能意义一直具有挑战性，因为很少有实验系统将大脑代谢模式与不同的行为状态联系起来。我们最近的转录组学分析建立了蜜蜂（Apis mellifera）攻击性与全脑氧化磷酸化活性降低之间的相关性，表明大脑代谢可塑性可能调节这种自然发生的行为。在这里，我们证明大脑新陈代谢和攻击性之间的关系是因果关系，在进化过程中保持不变，具有细胞类型特异性，并受到社会环境的调节。对蜜蜂进行药物治疗以抑制氧化磷酸化途径中的复合物 I 或 V 会导致攻击性增加。此外，转基因RNAi系和基因操作敲低果蝇（果蝇）神经元中复合物I的基因表达导致攻击性增加，但神经胶质细胞的敲低没有效果。最后，减少个体攻击性的蜂群水平的社会操作减弱了氧化磷酸化抑制对攻击性的影响，证明了社会环境对大脑功能的特定影响。由于神经元氧化磷酸化减少通常与脑部疾病有关，因此这些发现为理解大脑代谢可塑性和自然发生的行为可塑性提供了强有力的背景。
Despite ongoing high energetic demands, brains do not always use glucose and oxygen in a ratio that produces maximal ATP through oxidative phosphorylation. In some cases glucose consumption exceeds oxygen use despite adequate oxygen availability, a phenomenon known as aerobic glycolysis. Although metabolic plasticity seems essential for normal cognition, studying its functional significance has been challenging because few experimental systems link brain metabolic patterns to distinct behavioral states. Our recent transcriptomic analysis established a correlation between aggression and decreased whole-brain oxidative phosphorylation activity in the honey bee (Apis mellifera), suggesting that brain metabolic plasticity may modulate this naturally occurring behavior. Here we demonstrate that the relationship between brain metabolism and aggression is causal, conserved over evolutionary time, cell type-specific, and modulated by the social environment. Pharmacologically treating honey bees to inhibit complexes I or V in the oxidative phosphorylation pathway resulted in increased aggression. In addition, transgenic RNAi lines and genetic manipulation to knock down gene expression in complex I in fruit fly (Drosophila melanogaster) neurons resulted in increased aggression, but knockdown in glia had no effect. Finally, honey bee colony-level social manipulations that decrease individual aggression attenuated the effects of oxidative phosphorylation inhibition on aggression, demonstrating a specific effect of the social environment on brain function. Because decreased neuronal oxidative phosphorylation is usually associated with brain disease, these findings provide a powerful context for understanding brain metabolic plasticity and naturally occurring behavioral plasticity.