Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224, USA.
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nat Rev Neurosci. 2018 Feb;19(2):63-80. doi: 10.1038/nrn.2017.156. Epub 2018 Jan 11.
During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease.
在进化过程中，那些在禁食状态下大脑和身体功能良好的个体成功地获得了食物，从而得以生存和繁殖。禁食和长时间运动可耗尽肝糖原储存，并使酮体从脂肪细胞衍生的脂肪酸中产生。这种细胞燃料来源的代谢转换伴随着大脑神经网络的细胞和分子适应性增强，从而提高其功能并增强其对压力、损伤和疾病的抵抗力。在这里，我们考虑间歇性代谢转换如何优化大脑功能和韧性，即在整个生命周期中，重复代谢挑战的循环，诱导酮症（禁食和/或运动），然后是恢复期（进食、休息和睡眠），重点是参与认知和情绪的神经元回路。这种代谢转换会影响多种信号通路，从而促进大脑的神经可塑性和对损伤和疾病的抵抗力。
