Major depressive disorder mediates accelerated aging in rats subjected to chronic mild stress

2017 ◽  
Vol 329 ◽  
pp. 96-103 ◽  
Author(s):  
Xiaoxian Xie ◽  
Yangyang Chen ◽  
Lingyan Ma ◽  
Qichen Shen ◽  
Liangfeng Huang ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Accelerated Aging ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Major Depressive

scholarly journals Increased Neuronal DNA/RNA Oxidation in the Frontal Cortex of Mice Subjected to Unpredictable Chronic Mild Stress

2017 ◽  
Vol 1 ◽  
pp. 247054701772474 ◽  
Author(s):  
Alfred M. Maluach ◽  
Keith A. Misquitta ◽  
Thomas D. Prevot ◽  
Corey Fee ◽  
Etienne Sibille ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Frontal Cortex ◽  
Chronic Stress ◽  
Basolateral Amygdala ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Major Depressive ◽  
Unpredictable Chronic Mild Stress ◽  
Rna Oxidation

Background Chronic stress is implicated in the development of various psychiatric illnesses including major depressive disorder. Previous reports suggest that patients with major depressive disorder have increased levels of oxidative stress, including higher levels of DNA/RNA oxidation found in postmortem studies, especially within brain regions responsible for the cognitive and emotional processes disrupted in the disorder. Here, we aimed to investigate whether unpredictable chronic mild stress in mice induces neuronal DNA/RNA oxidation in the prelimbic, infralimbic, and cingulate cortices of the frontal cortex and the basolateral amygdala and to explore potential associations with depressive-like behaviors. We expected that animals subjected to unpredictable chronic mild stress will present higher levels of DNA/RNA oxidation, which will be associated with anxiety-/depressive-like behaviors. Methods C57BL/6J mice were assigned to unpredictable chronic mild stress or nonstress conditions (n = 10/group, 50% females). Following five weeks of unpredictable chronic mild stress exposure, mice were tested in a series of behavioral tests measuring anxiety- and depressive-like behaviors. Frontal cortex and amygdala sections were then immunolabeled for neuronal nuclei, a marker of post-mitotic neurons and anti-8-hydroxy-2-deoxyguanosine/8-oxo-7,8-dihydroguanosine, which reflects both DNA and RNA oxidation. Results Levels of neuronal DNA/RNA oxidation were increased in the frontal cortex of mice subjected to unpredictable chronic mild stress ( p = 0.0207). Levels of neuronal DNA/RNA oxidation in the frontal cortex were positively correlated with z-emotionality scores for latency to feed in the novelty-suppressed feeding test ( p = 0.0031). Statistically significant differences were not detected in basolateral amygdala levels of neuronal DNA/RNA oxidation between nonstress- and unpredictable chronic mild stress-exposed mice, nor were correlations found with behavioral performances for this region. Conclusion Our results demonstrate that unpredictable chronic mild stress induces a significant increase in neuronal DNA/RNA oxidation in the frontal cortex that correlate with behavioral readouts of the stress response. A lack of DNA/RNA oxidation alterations in the basolateral amygdala suggests greater vulnerability of frontal cortex neurons to DNA/RNA oxidation in response to unpredictable chronic mild stress. These findings add support to the hypothesis that chronic stress-induced damage to DNA/RNA may be an additional molecular mechanism underlying cellular dysfunctions associated with chronic stress and present in stress-related disorders.

A metabolomics-based approach for ranking the depressive level in a chronic unpredictable mild stress rat model

RSC Advances ◽  
2016 ◽  
Vol 6 (31) ◽  
pp. 25751-25765 ◽  
Author(s):  
Xinyu Yu ◽  
Shanlei Qiao ◽  
Di Wang ◽  
Jiayong Dai ◽  
Jun Wang ◽  
...  
Keyword(s):  
Animal Model ◽  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Depressive Disorder ◽  
Rat Model ◽  
Untargeted Metabolomics ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Major Depressive ◽  
Metabolomics Study

An untargeted metabolomics study to investigate the metabolome change in plasma, hippocampus and prefrontal cortex (PFC) in an animal model with a major depressive disorder (MDD) had been conducted.

scholarly journals Molecular mechanism of reward treatment ameliorating chronic stress-induced depressive-like behavior assessed by sequencing miRNA and mRNA in medial prefrontal cortex

2020 ◽  
Author(s):  
Tingting An ◽  
Zhenhua Song ◽  
Jin-Hui Wang
Keyword(s):  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Depressive Disorder ◽  
Molecular Mechanism ◽  
Chronic Stress ◽  
Medial Prefrontal Cortex ◽  
Differentially Expressed ◽  
Mild Stress ◽  
Major Depressive ◽  
Differentially Expressed Mirnas

Abstract Background Major depressive disorder (MDD) is a disease that seriously endangers human health and mental state. Chronic stress and lack of reward may reduce the function of the brain's reward circuits, leading to major depressive disorder. The effect of reward treatment on chronic stress-induced depression-like behaviors and its molecular mechanism in the brain remain unclear.Methods Mice were divided into the groups of control, chronic unpredictable mild stress (CUMS), and CUMS-companion. Mice of CUMS group was performed by CUMS for 4 weeks, and CUMS-companion group was treated by CUMS accompanied with companion. The tests of sucrose preference, Y-maze, and forced swimming were conducted to assess depression-like behaviors or resilience. High-throughput sequencing was used to analyze mRNA and miRNA profiles in the medial prefrontal cortex harvested from control, CUMS-MDD (mice with depression-like behaviors in CUMS group), Reward-MDD (mice with depression-like behaviors in CUMS-companion group), CUMS-resilience (resilient mice in CUMS group), Reward-resilience (resilient mice in CUMS-companion group) mice.Results The results provided evidence that accompanying with companion ameliorated CUMS-induced depression-like behaviors in mice. 45 differentially expressed genes (DEGs) are associated with depression-like behaviors, 8 DEGs are associated with resilience and 59 DEGs are associated with nature reward (companion) were identified. Furthermore, 196 differentially expressed miRNAs were found to be associated with companion. Based on the differentially expressed miRNAs and DEGs data, miRNA-mRNA network was established to be associated with companion.Conclusion Taken together, our data here provided a method to ameliorate depression-like behaviors, and numerous potential drug targets for the prevention or treatment of depression.

scholarly journals Accelerated aging of the putamen in patients with major depressive disorder

2017 ◽  
Vol 42 (3) ◽  
pp. 164-171 ◽  
Author(s):  
Matthew D. Sacchet ◽  
M. Catalina Camacho ◽  
Emily E. Livermore ◽  
Ewart A.C. Thomas ◽  
Ian H. Gotlib
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Accelerated Aging ◽  
Major Depressive

The role of oxidative and nitrosative stress in accelerated aging and major depressive disorder

2016 ◽  
Vol 65 ◽  
pp. 134-144 ◽  
Author(s):  
Pawan Kumar Maurya ◽  
Cristiano Noto ◽  
Lucas B. Rizzo ◽  
Adiel C. Rios ◽  
Sandra O.V. Nunes ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Nitrosative Stress ◽  
Accelerated Aging ◽  
Major Depressive ◽  
Oxidative And Nitrosative Stress

scholarly journals Transthyretin as a Biomarker to Predict and Monitor Major Depressive Disorder Identified by Whole-Genome Transcriptomic Analysis in Mouse Models

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1124
Author(s):  
Sung-Liang Yu ◽  
Selina Shih-Ting Chu ◽  
Min-Hui Chien ◽  
Po-Hsiu Kuo ◽  
Pan-Chyr Yang ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Hedgehog Signaling ◽  
Stressful Life Events ◽  
Genomic Analysis ◽  
Enrichment Analysis ◽  
Transcriptomic Analysis ◽  
Molecular Networks ◽  
Mild Stress ◽  
Major Depressive

Background: Accumulations of stressful life events result in the onset of major depressive disorder (MDD). Comprehensive genomic analysis is required to elucidate pathophysiological changes and identify applicable biomarkers. Methods: Transcriptomic analysis was performed on different brain parts of a chronic mild stress (CMS)-induced MDD mouse model followed by systemic analysis. QPCR and ELISA were utilized for validation in mice and patients. Results: The highest numbers of genes with significant changes induced by CMS were 505 in the amygdala followed by 272 in the hippocampus (twofold changes; FDR, p < 0.05). Enrichment analysis indicated that the core-enriched genes in CMS-treated mice were positively enriched for IFN-γ response genes in the amygdala, and hedgehog signaling in the hippocampus. Transthyretin (TTR) was severely reduced in CMS-treated mice. In patients with diagnosed MDD, serum concentrations of TTR were reduced by 48.7% compared to controls (p = 0.0102). Paired samples from patients with MDD demonstrated a further 66.3% increase in TTR at remission compared to the acute phase (p = 0.0339). Conclusions: This study provides comprehensive information on molecular networks related to MDD as a basis for further investigation and identifies TTR for MDD monitoring and management. A clinical trial with bigger patient cohort should be conducted to validate this translational study.

Peripheral blood mononuclear cell-based metabolomic profiling of a chronic unpredictable mild stress rat model of depression

2014 ◽  
Vol 10 (11) ◽  
pp. 2994-3001 ◽  
Author(s):  
Juan Li ◽  
Ge Tang ◽  
Ke Cheng ◽  
Deyu Yang ◽  
Guanghui Chen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Peripheral Blood Mononuclear Cell ◽  
Depressive Disorder ◽  
Rat Model ◽  
Peripheral Blood ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Major Depressive ◽  
Peripheral Blood Mononuclear ◽  
Metabolomic Profiling

Major depressive disorder (MDD) is a debilitating mood disorder with various etiopathological hypotheses.

scholarly journals “GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ekaterina Protsenko ◽  
Ruoting Yang ◽  
Brent Nier ◽  
Victor Reus ◽  
Rasha Hammamieh ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Smoking Status ◽  
Accelerated Aging ◽  
Premature Mortality ◽  
Cellular Aging ◽  
Psychiatric Disease ◽  
Healthy Controls ◽  
Major Depressive ◽  
Age Related

AbstractMajor depressive disorder (MDD) is associated with premature mortality and is an independent risk factor for a broad range of diseases, especially those associated with aging, such as cardiovascular disease, diabetes, and Alzheimer’s disease. However, the pathophysiology underlying increased rates of somatic disease in MDD remains unknown. It has been proposed that MDD represents a state of accelerated cellular aging, and several measures of cellular aging have been developed in recent years. Among such metrics, estimators of biological age based on predictable age-related patterns of DNA methylation (DNAm), so-called ‘epigenetic clocks’, have shown particular promise for their ability to capture accelerated aging in psychiatric disease. The recently developed DNAm metric known as ‘GrimAge’ is unique in that it was trained on time-to-death data and has outperformed its predecessors in predicting both morbidity and mortality. Yet, GrimAge has not been investigated in MDD. Here we measured GrimAge in 49 somatically healthy unmedicated individuals with MDD and 60 age-matched healthy controls. We found that individuals with MDD exhibited significantly greater GrimAge relative to their chronological age (‘AgeAccelGrim’) compared to healthy controls (p = 0.001), with a median of 2 years of excess cellular aging. This difference remained significant after controlling for sex, current smoking status, and body-mass index (p = 0.015). These findings are consistent with prior suggestions of accelerated cellular aging in MDD, but are the first to demonstrate this with an epigenetic metric predictive of premature mortality.

scholarly journals Age-Related Decrease in Default-Mode Network Functional Connectivity Is Accelerated in Patients With Major Depressive Disorder

2022 ◽  
Vol 13 ◽  
Author(s):  
Shixiong Tang ◽  
Zhipeng Wu ◽  
Hengyi Cao ◽  
Xudong Chen ◽  
Guowei Wu ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Default Mode Network ◽  
Regression Models ◽  
Accelerated Aging ◽  
Major Depressive ◽  
Default Mode ◽  
Age Related ◽  
Main Effect

Major depressive disorder (MDD) is a common psychiatric disorder which is associated with an accelerated biological aging. However, little is known whether such process would be reflected by a more rapid aging of the brain function. In this study, we tested the hypothesis that MDD would be characterized by accelerated aging of the brain’s default-mode network (DMN) functions. Resting-state functional magnetic resonance imaging data of 971 MDD patients and 902 healthy controls (HCs) was analyzed, which was drawn from a publicly accessible, multicenter dataset in China. Strength of functional connectivity (FC) and temporal variability of dynamic functional connectivity (dFC) within the DMN were calculated. Age-related effects on FC/dFC were estimated by linear regression models with age, diagnosis, and diagnosis-by-age interaction as variables of interest, controlling for sex, education, site, and head motion effects. The regression models revealed (1) a significant main effect of age in the predictions of both FC strength and dFC variability; and (2) a significant main effect of diagnosis and a significant diagnosis-by-age interaction in the prediction of FC strength, which was driven by stronger negative correlation between age and FC strength in MDD patients. Our results suggest that (1) both healthy participants and MDD patients experience decrease in DMN FC strength and increase in DMN dFC variability along age; and (2) age-related decrease in DMN FC strength may occur at a faster rate in MDD patients than in HCs. However, further longitudinal studies are still needed to understand the causation between MDD and accelerated aging of brain.

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