School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Department of Pediatrics, Hospital of Nanjing University of Chinese Medicine, Nanjing, 210004, China.
Psychopharmacology (Berl). 2022 Mar;239(3):729-743. doi: 10.1007/s00213-021-05958-w. Epub 2022 Feb 8.
Major depressive disorder is a leading cause of disability worldwide, affecting up to 17 % of the general population. The neural mechanisms of depression, however, are yet to be uncovered. Recently, attention has been drawn to the effects of dysfunctional brain-gut axis on depression, and many substances have been suggested to be involved in the communication between the gut and brain, such as ghrelin.
We herein systematically examined the changes of metabolomics after unpredictable chronic mild stress (UCMS)-induced depression-like behaviors in rats and compared the altered metabolites in the hippocampus and jejunum samples.
Our results show that many metabolites significantly changed with UCMS both in the hippocampus and jejunum, such as L-glutamine, L-tyrosine, hydroxylamine, and 3-phosphoglyceric acid. Further studies suggested that these changes are the reasons for anxiety-like behaviors and depression-like behaviors in UCMS rats and also are the reasons for hippocampal neural plasticity.
Coexistence of brain and gut metabolic changes in UCMS-induced depressive behavior in rats suggests a possible role of brain-gut axis in depression. This study provides insights into the neurobiology of depression.
重度抑郁症是全球范围内导致残疾的主要原因,影响了高达 17%的普通人群。然而,抑郁症的神经机制仍未被揭示。最近,人们对功能失调的脑-肠轴对抑郁症的影响引起了关注,许多物质被认为参与了肠道与大脑之间的通讯,例如胃饥饿素。
我们在此系统地检查了不可预测的慢性轻度应激(UCMS)诱导的抑郁样行为后大鼠的代谢组学变化,并比较了海马体和空肠样本中改变的代谢物。
我们的结果表明,UCMS 后许多代谢物在海马体和空肠中都发生了显著变化,如 L-谷氨酰胺、L-酪氨酸、羟胺和 3-磷酸甘油酸。进一步的研究表明,这些变化是 UCMS 大鼠出现焦虑样行为和抑郁样行为的原因,也是海马体神经可塑性的原因。
UCMS 诱导的抑郁行为大鼠中脑和肠道代谢变化的共存表明脑-肠轴在抑郁症中的可能作用。这项研究为抑郁症的神经生物学提供了新的见解。