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.

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.

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

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.

Shared Transcriptional Signatures in Major Depressive Disorder and Mouse Chronic Stress Models

2020 ◽  
Vol 87 (9) ◽  
pp. S222
Author(s):  
Joseph Scarpa ◽  
Mena Fatma ◽  
Yong-Hwee E. Loh ◽  
Said Romaric Traore ◽  
Théo Stefan ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Chronic Stress ◽  
Major Depressive ◽  
Stress Models

scholarly journals Regionally specific alterations in functional connectivity of the anterior cingulate cortex in major depressive disorder

2012 ◽  
Vol 42 (10) ◽  
pp. 2071-2081 ◽  
Author(s):  
C. G. Davey ◽  
B. J. Harrison ◽  
M. Yücel ◽  
N. B. Allen
Keyword(s):  
Major Depressive Disorder ◽  
Functional Connectivity ◽  
Depressive Disorder ◽  
Frontal Cortex ◽  
Caudate Nucleus ◽  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Major Depressive ◽  
Close Link

BackgroundDepression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally diverse subregions of the rostral cingulate cortex.MethodEighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups.ResultsThe depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally.ConclusionsThe results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect; and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.

scholarly journals Characterization of GABAergic Marker Expression in the Chronic Unpredictable Stress Model of Depression

2017 ◽  
Vol 1 ◽  
pp. 247054701772045 ◽  
Author(s):  
Mounira Banasr ◽  
Ashley Lepack ◽  
Corey Fee ◽  
Vanja Duric ◽  
Jaime Maldonado-Aviles ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Depressive Disorder ◽  
Protein Expression ◽  
Neuropeptide Y ◽  
Chronic Stress ◽  
Gabaergic Interneurons ◽  
Chronic Unpredictable Stress ◽  
Major Depressive

Background Evidence continues to build suggesting that the GABAergic neurotransmitter system is altered in brains of patients with major depressive disorder. However, there is little information available related to the extent of these changes or the potential mechanisms associated with these alterations. As stress is a well-established precipitant to depressive episodes, we sought to explore the impact of chronic stress on GABAergic interneurons. Methods Using western blot analyses and quantitative real-time polymerase chain reaction, we assessed the effects of five-weeks of chronic unpredictable stress exposure on the expression of GABA-synthesizing enzymes (GAD65 and GAD67), calcium-binding proteins (calbindin, parvalbumin, and calretinin), and neuropeptides co-expressed in GABAergic neurons (somatostatin, neuropeptide Y, vasoactive intestinal peptide, and cholecystokinin) in the prefrontal cortex and hippocampus of rats. We also investigated the effects of corticosterone and dexamethasone exposure on these markers in vitro in primary cortical and hippocampal cultures. Results We found that chronic unpredictable stress induced significant reductions of GAD67 protein levels in both the prefrontal cortex and hippocampus of chronic unpredictable stress-exposed rats but did not detect changes in GAD65 protein expression. Similar protein expression changes were found in vitro in cortical neurons. In addition, our results provide clear evidence of reduced markers of interneuron population(s), namely somatostatin and neuropeptide Y, in the prefrontal cortex, suggesting these cell types may be selectively vulnerable to chronic stress. Conclusion Together, this work highlights that chronic stress induces regional and cell type-selective effects on GABAergic interneurons in rats. These findings provide additional supporting evidence that stress-induced GABA neuron dysfunction and cell vulnerability play critical roles in the pathophysiology of stress-related illnesses, including major depressive disorder.

scholarly journals Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Anastasiya Kasian ◽  
Timur Kolomin ◽  
Lyudmila Andreeva ◽  
Elena Bondarenko ◽  
Nikolay Myasoedov ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Anxiolytic Effect ◽  
Chronic Mild Stress ◽  
Stress Conditions ◽  
Mild Stress ◽  
Unpredictable Chronic Mild Stress ◽  
Elevated Plus Maze Test ◽  
Plus Maze ◽  
The Individual ◽  
Benzodiazepine Drugs

It was shown that the anxiolytic effect of Selank is comparable to that of classical benzodiazepine drugs and that the basis of their mechanism of action may be similar. These data suggest that the presence of Selank may change the action of classical benzodiazepine drugs. To test this hypothesis, we evaluated the anxiolytic activity of Selank and diazepam in rats both under conditions of unpredictable chronic mild stress and in its absence, after the individual and combined administration of these compounds using the elevated plus maze test. We found that, even in the absence of chronic stress, the administration of a course of test substances changed anxiety indicators toward their deterioration, but the changes after the administration of a course of Selank were less pronounced. In conditions of chronic stress, anxiety indicator values after the simultaneous use of diazepam and Selank did not differ from the respective values observed before chronic stress exposure. The data obtained indicate that the individual administration of Selank was the most effective in reducing elevated levels of anxiety, induced by the administration of a course of test substances, whereas the combination of diazepam with Selank was the most effective in reducing anxiety in unpredictable chronic mild stress conditions.

scholarly journals Central and Peripheral Inflammation Link Metabolic Syndrome and Major Depressive Disorder

Physiology ◽  
2019 ◽  
Vol 34 (2) ◽  
pp. 123-133 ◽  
Author(s):  
Kenny L. Chan ◽  
Flurin Cathomas ◽  
Scott J. Russo
Keyword(s):  
Metabolic Syndrome ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Chronic Stress ◽  
Immune Cells ◽  
Low Grade ◽  
Major Depressive ◽  
Metabolic Dysregulation ◽  
Critical Areas ◽  
Behavioral Abnormalities

Metabolic syndrome and major depression are two of the most common and debilitating disorders worldwide, occurring with significant rates of comorbidity. Recent studies have uncovered that each of these conditions is associated with chronic, low-grade inflammation. This is characterized by increased circulating pro-inflammatory cytokines, altered leukocyte population frequencies in blood, accumulation of immune cells in tissues including the brain, and activation of these immune cells. Cytokines that become elevated during obesity can contribute to the progression of metabolic syndrome by directly causing insulin resistance. During chronic stress, there is evidence that these cytokines promote depression-like behavior by disrupting neurotransmitter synthesis and signal transduction. Animal models of obesity and depression have revealed a bi-directional relationship whereby high-fat feeding and chronic stress synergize and exacerbate metabolic dysregulation and behavioral abnormalities. Although far from conclusive, emerging evidence suggests that inflammation in the central and peripheral immune system may link metabolic syndrome to major depressive disorder. In this review, we will synthesize available data supporting this view and identify critical areas for future investigation.

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