Metabolomics Analysis of the Prefrontal Cortex in a Rat Chronic Unpredictable Mild Stress Model of Depression

Abstract

Background:Depressive disorder is the leading cause of disability and suicidality worldwide. Metabolites are considered indicators and regulators of depression. However, the pathophysiology of the prefrontal cortex (PFC) in depression remains unclear.MethodsA chronic unpredictable mild stress (CUMS) model and a maturation rodent model of depression was used to investigate metabolic changes in the PFC. Eighteen male Sprague-Dawley rats were randomly divided into CUMS and control groups. The sucrose preference test (SPT) and forced swimming test (FST) were employed to evaluate and record depression-associated behaviors and changes in body weight (BW). High-performance liquid chromatography–tandem mass spectrometry was applied to test metabolites in rat PFC. Furthermore, principal component analysis and orthogonal partial least-squares discriminant analysis were employed to identify differentially abundant metabolites. Metabolic pathways were analyzed using MetaboAnalyst. Finally, a metabolite-protein interaction network was established to illustrate the function of differential metabolites.ResultsSPT and FST results confirmed successful establishment of the CUMS-induced depression-like behavior model in rats. Five metabolites, including 1-methylnicotinamide, 3-methylhistidine, acetylcholine, glycerophospho-N-palmitoyl ethanolamine, α-D-mannose 1-phosphate, were identified as potential biomarkers of depression. Four pathways changed in the CUMS group. Metabolite-protein interaction analysis revealed that 10 pathways play roles in the metabolism of depression.ConclusionFive potential biomarkers were identified in the PFC and metabolite-protein interactions associated with metabolic pathophysiological processes were explored using the CUMS model. The results of this study will assist physicians and scientists in discovering potential diagnostic markers and novel therapeutic targets for depression.

13-cis-Retinoic Acid Affects Brain Perfusion and Function: In Vivo Study

“…Model. The unpredictable mild stress model was followed, as described by [36][37][38], with timing modifications. The remaining animals assigned to the stress group were exposed to one dose of 0.4 mg/kg of 13-RA subcutaneously for seven consecutive days compared to C group, which was given 0 mg of 13-RA per kg of body weight.…”

β-Asarone Promotes Autophagy by Inhibiting the PI3K/Akt/mTOR Pathway in a Rat Model of Depression in Parkinson’s Disease

“…The CUMS procedure was modi ed from previously published reports [31][32]. Except for the shamoperated group, all experimental animals were exposed to a series of mild stressors including (1) cage tilt (45°) for 24 h, (2) food deprivation for 24 h, (3) water deprivation for 24 h, (4) tail clamping for 3 min, (5) soiled cage (500 mL of water in 100 g maize-cob bedding) for 24 h, (6) overnight illumination, and (7) forced swimming at 4 °C for 5 min.…”

Dulaglutide treatment reverses depression‐like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress

“…The chronic mild stress (CMS) model is recognized as a reliable and practical rodent model of depression. As a result, it is broadly used to study the role of stress in the etiology of depression (Duan et al, 2022;Faria et al, 2014;Willner P., 2017).…”

“…The chronic mild stress (CMS) model is recognized as a reliable and practical rodent model of depression. As a result, it is broadly used to study the role of stress in the etiology of depression (Duan et al., 2022 ; Faria et al., 2014 ; Willner P., 2017 ). The hippocampus is a complex brain region involved in depression that exhibits morphological and functional alterations in response to stress (Zhang et al., 2022 ).…”