Neurotransmission is an energetically expensive process that underlies cognition. During intense electrical activity or dietary restrictions, the glucose level in the brain plummets, forcing neurons to utilize alternative fuels. However, the molecular mechanisms of neuronal metabolic plasticity remain poorly understood. Here, we demonstrate that glucose-deprived neurons activate the CREB and PGC1α transcriptional program, which induces expression of the mitochondrial deacetylase Sirtuin 3 (Sirt3) both in vitro and in vivo. We show that Sirt3 localizes to axonal mitochondria and stimulates mitochondrial oxidative capacity in hippocampal nerve terminals. Sirt3 plays an essential role in sustaining synaptic transmission in the absence of glucose by providing metabolic support for the retrieval of synaptic vesicles after release. These results demonstrate that the transcriptional induction of Sirt3 facilitates the metabolic plasticity of synaptic transmission.

中文翻译：

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Sirtuin3 确保葡萄糖剥夺过程中神经传递的代谢可塑性


神经传递是一个能量昂贵的过程，是认知的基础。在剧烈的电活动或饮食限制期间，大脑中的葡萄糖水平会直线下降，迫使神经元使用替代燃料。然而，神经元代谢可塑性的分子机制仍然知之甚少。在这里，我们证明葡萄糖剥夺神经元激活 CREB 和 PGC1α 转录程序，该程序在体外和体内诱导线粒体脱乙酰酶 Sirtuin 3 （Sirt3） 的表达。我们表明 Sirt3 定位于轴突线粒体并刺激海马神经末梢的线粒体氧化能力。Sirt3 通过为释放后突触小泡的恢复提供代谢支持，在缺乏葡萄糖的情况下维持突触传递中起着重要作用。这些结果表明，Sirt3 的转录诱导促进了突触传递的代谢可塑性。