title: Unpredictable chronic mild stress induces anxiety and depression-like behaviors and inactivates AMP-activated protein kinase in mice.
abstract: The unpredictable chronic mild stress (UCMS) model was developed based upon the stress-diathesis hypothesis of depression. Most effects of UCMS can be reversed by antidepressants, demonstrating a strong predictive validity of this model for depression. However, the mechanisms underlying the effects induced by UCMS remain incompletely understood. Increasing evidence has shown that AMP-activated protein kinase (AMPK) regulates intracellular energy metabolism and is especially important for neurons because neurons are known to have small energy reserves. Abnormalities in the AMPK pathway disturb normal brain functions and synaptic integrity. In the present study, we first investigated the effects of UCMS on a battery of different tests measuring anxiety and depression-like behaviors in female C57BL/6N mice after 4 weeks of UCMS exposure. Stressed mice showed suppressed body weight gain, heightened anxiety, and increased immobility in the forced swim and tail suspension tests. These results are representative of some of the core symptoms of depression. Simultaneously, we observed decrease of synaptic proteins in the cortex of mice subjected to UCMS, which is associated with decreased levels of phosphorylated AMP-activated protein kinase α (AMPKα) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase). Our findings suggest that AMPKα inactivation might be a mechanism by which UCMS causes anxiety/depression-like behaviors in mice.
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Shenghua
authors: S
authors: Zhu
authors: Mental Health Center, Shantou University, Shantou, Guangdong, China; Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors: Junhui
authors: J
authors: Wang
authors: Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors: Yanbo
authors: Y
authors: Zhang
authors: Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Victor
authors: V
authors: Li
authors: Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Jiming
authors: J
authors: Kong
authors: First Affiliated Hospital, Henan University, Kaifeng, Henan, China.
authors: Jue
authors: J
authors: He
authors: Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address: xinmin@ualberta.ca.
authors: Xin-Min
authors: XM
authors: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000201:enzymology / Q000209:etiology*; D001835:Body Weight; D002540:Cerebral Cortex / Q000201:enzymology*; D003863:Depression / Q000201:enzymology / Q000209:etiology*; D004789:Enzyme Activation; D005106:Exploratory Behavior; D005247:Feeding Behavior; D005260:Female; D006380:Helplessness, Learned; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications* / Q000201:enzymology
chemical_list: D009419:Nerve Tissue Proteins; D006903:Hydroxymethylglutaryl CoA Reductases; D055372:AMP-Activated Protein Kinases
keywords: Adenosine monophosphate-activated protein kinase; Anxiety; Depression; Unpredictable chronic mild stress