Laboratory for Functional and Metabolic Imaging (LIFMET), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Laboratory of Behavioral Genetics, Brain and Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Elife. 2020 Jan 10;9:e50631. doi: 10.7554/eLife.50631.
Emerging evidence suggests that hierarchical status provides vulnerability to develop stress-induced depression. Energy metabolic changes in the nucleus accumbens (NAc) were recently related to hierarchical status and vulnerability to develop depression-like behavior. Acetyl-L-carnitine (LAC), a mitochondria-boosting supplement, has shown promising antidepressant-like effects opening therapeutic opportunities for restoring energy balance in depressed patients. We investigated the metabolic impact in the NAc of antidepressant LAC treatment in chronically-stressed mice using H-magnetic resonance spectroscopy (H-MRS). High rank, but not low rank, mice, as assessed with the tube test, showed behavioral vulnerability to stress, supporting a higher susceptibility of high social rank mice to develop depressive-like behaviors. High rank mice also showed reduced levels of several energy-related metabolites in the NAc that were counteracted by LAC treatment. Therefore, we reveal a metabolic signature in the NAc for antidepressant-like effects of LAC in vulnerable mice characterized by restoration of stress-induced neuroenergetics alterations and lipid function.
新出现的证据表明，等级地位使人易患应激引起的抑郁症。伏隔核（NAc）中的能量代谢变化与等级地位和易患抑郁症样行为有关。乙酰-L-肉碱（LAC）是一种线粒体增强补充剂，具有有希望的抗抑郁样作用，为恢复抑郁患者的能量平衡提供了治疗机会。我们使用 H 磁共振波谱（H-MRS）研究了慢性应激小鼠中抗抑郁 LAC 治疗对 NAc 的代谢影响。通过管试验评估，高等级但不是低等级的小鼠表现出对压力的行为脆弱性，这支持了高社会等级的小鼠更容易发展出抑郁样行为的更高易感性。高等级的小鼠的 NAc 中也显示出几种与能量相关的代谢物水平降低，而 LAC 治疗则可以逆转这种情况。因此，我们揭示了 LAC 在易受伤害的小鼠中具有抗抑郁样作用的 NAc 代谢特征，表现为应激诱导的神经能量改变和脂质功能的恢复。
