scholarly journals Chronic stress impairs male spermatogenesis function and nectin-3 protein expression in the testis

2020 ◽  
pp. 297-306
Author(s):  
T. Li ◽  
J. Yao ◽  
Q. Zhang ◽  
Q. Li ◽  
J. Li ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Molecular Mechanisms ◽  
Social Defeat ◽  
Histological Structure ◽  
Male Mice ◽  
Corticotropin Releasing Hormone ◽  
Social Defeat Stress ◽  
Control Male ◽  
Releasing Hormone ◽  
Chronic Social Defeat Stress

Chronic stress is a crucial public issue that occurs when a person is repetitively stimulated by various stressors. Previous researches have reported that chronic stress induces spermatogenesis dysfunction in the reproductive system, but its molecular mechanisms remain unclear. The nectin protein family, including nectin-1 to nectin-4, is Ca(2+)-independent immunoglobulin-like cell adhesion molecules, that are widely expressed in the hippocampus, testicular tissue, epithelial cells and other sites. Nectin-3 contributes to the sperm development at the late stage, and the abnormal expression of nectin-3 impairs spermatogenesis. Some recent studies have demonstrated that stress induces a decrease in nectin-3 expression in the hippocampus via corticotropin-releasing hormone (CRH) to corticotropin-releasing hormone receptor 1 (CRHR1) pathway. Here, we tested whether chronic stress also caused a reduction in nectin-3 expression in the testis. We established a chronic social defeat stress paradigm, which provides naturalistic and complex chronic stress in male C57BL/6 mice. After 25 days of chronic social defeat stress, the mice showed weight loss, thymic atrophy and some other typical symptoms of chronic stress (e.g. anxiety-like behavior and social avoidance behavior). We found gonad atrophy, testicular histological structure changes and semen quality reductions in the stressed mice. The stressed male mice significantly spent more time to impregnate the female mice than the control male mice. Moreover, nectin-3 protein levels in stressed mice were significantly decreased in the testes compared with those in control mice. In addition, we found that the CRHR1 expression level was increased in the testes of stressed mice. Therefore, we demonstrated a decreased level of nectin-3 expression and an increase in CRHR1 expression in the testis after exposure to chronic stress, which may provide a potential therapeutic target for the spermatogenesis dysfunction induced by chronic stress.

scholarly journals Dysfunction in Ribosomal Gene Expression in the Hypothalamus and Hippocampus following Chronic Social Defeat Stress in Male Mice as Revealed by RNA-Seq

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Dmitry A. Smagin ◽  
Irina L. Kovalenko ◽  
Anna G. Galyamina ◽  
Anatoly O. Bragin ◽  
Yuriy L. Orlov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Stress ◽  
Ribosome Biogenesis ◽  
Social Defeat ◽  
Brain Regions ◽  
Ribosomal Gene ◽  
Rna Seq ◽  
Male Mice ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress

Chronic social defeat stress leads to the development of anxiety- and depression-like states in male mice and is accompanied by numerous molecular changes in brain. The influence of 21-day period of social stress on ribosomal gene expression in five brain regions was studied using the RNA-Seq database. MostRps, Rpl, Mprs, andMprlgenes were upregulated in the hypothalamus and downregulated in the hippocampus, which may indicate ribosomal dysfunction following chronic social defeat stress. There were no differentially expressed ribosomal genes in the ventral tegmental area, midbrain raphe nuclei, or striatum. This approach may be used to identify a pharmacological treatment of ribosome biogenesis abnormalities in the brain of patients with “ribosomopathies.”

scholarly journals LIMK1/2 in the mPFC Plays a Role in Chronic Stress-Induced Depressive-Like Effects in Mice

2020 ◽  
Vol 23 (12) ◽  
pp. 821-836
Author(s):  
Ting-Ting Gao ◽  
Yuan Wang ◽  
Ling Liu ◽  
Jin-Liang Wang ◽  
Ying-Jie Wang ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Restraint Stress ◽  
Social Defeat ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Chronic Restraint Stress ◽  
Lim Domain ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress ◽  
Pharmacological Target

Abstract Background Depression is one of the most common forms of mental illness and also a leading cause of disability worldwide. Developing novel antidepressant targets beyond the monoaminergic systems is now popular and necessary. LIM kinases, including LIM domain kinase 1 and 2 (LIMK1/2), play a key role in actin and microtubule dynamics through phosphorylating cofilin. Since depression is associated with atrophy of neurons and reduced connectivity, here we speculate that LIMK1/2 may play a role in the pathogenesis of depression. Methods In this study, the chronic unpredictable mild stress (CUMS), chronic restraint stress (CRS), and chronic social defeat stress (CSDS) models of depression, various behavioral tests, stereotactic injection, western blotting, and immunofluorescence methods were adopted. Results CUMS, CRS, and CSDS all significantly enhanced the phosphorylation levels of LIMK1 and LIMK2 in the medial prefrontal cortex (mPFC) but not the hippocampus of mice. Administration of fluoxetine, the most commonly used selective serotonin reuptake inhibitor in clinical practice, fully reversed the effects of CUMS, CRS, and CSDS on LIMK1 and LIMK2 in the mPFC. Moreover, pharmacological inhibition of LIMK1 and LIMK2 in the mPFC by LIMKi 3 infusions notably prevented the pro-depressant effects of CUMS, CRS, and CSDS in mice. Conclusions In summary, these results suggest that LIMK1/2 in the mPFC has a role in chronic stress-induced depressive-like effects in mice and could be a novel pharmacological target for developing antidepressants.

Changes in the expression of dopaminergic genes in brain structures of male mice exposed to chronic social defeat Stress: An RNA-seq study

2016 ◽  
Vol 50 (1) ◽  
pp. 161-163 ◽  
Author(s):  
I. L. Kovalenko ◽  
D. A. Smagin ◽  
A. G. Galyamina ◽  
Yu. L. Orlov ◽  
N. N. Kudryavtseva
Keyword(s):  
Social Defeat ◽  
Brain Structures ◽  
Rna Seq ◽  
Male Mice ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress ◽  
Dopaminergic Genes

scholarly journals Chronic Social Defeat Stress Modulates Dendritic Spines Structural Plasticity in Adult Mouse Frontal Association Cortex

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Yu Shu ◽  
Tonghui Xu
Keyword(s):  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Structural Plasticity ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress ◽  
Stress Experience ◽  
Spine Dynamics

Chronic stress is associated with occurrence of many mental disorders. Previous studies have shown that dendrites and spines of pyramidal neurons of the prefrontal cortex undergo drastic reorganization following chronic stress experience. So the prefrontal cortex is believed to play a key role in response of neural system to chronic stress. However, how stress induces dynamic structural changes in neural circuit of prefrontal cortex remains unknown. In the present study, we examined the effects of chronic social defeat stress on dendritic spine structural plasticity in the mouse frontal association (FrA) cortexin vivousing two-photon microscopy. We found that chronic stress altered spine dynamics in FrA and increased the connectivity in FrA neural circuits. We also found that the changes in spine dynamics in FrA are correlated with the deficit of sucrose preference in defeated mice. Our findings suggest that chronic stress experience leads to adaptive change in neural circuits that may be important for encoding stress experience related memory and anhedonia.

scholarly journals Splenic NKG2D confers resilience versus susceptibility in mice after chronic social defeat stress: beneficial effects of (R)-ketamine

2019 ◽  
Author(s):  
Kai Zhang ◽  
Akemi Sakamoto ◽  
Lijia Chang ◽  
Youge Qu ◽  
Siming Wang ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Molecular Mechanisms ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
Beneficial Effects ◽  
Nkg2d Expression ◽  
Chronic Social Defeat Stress ◽  
Group 2 ◽  
Stress Susceptibility

AbstractThe spleen is a large immune organ that plays a key role in the immune system. The precise molecular mechanisms underlying the relationship between the spleen and stress-related psychiatric disorders are unknown. Here we investigated the role of spleen in stress-related psychiatric disorders. FACS analysis was applied to determine the contribution of the spleen to susceptibility and resilience in mice that were subjected to chronic social defeat stress (CSDS). We found a notable increase in splenic volume and weight in CSDS-susceptible mice compared to control (no CSDS) mice and CSDS-resilient mice. The number of granulocytes, but not of T cells and B cells, in the spleen of susceptible mice was higher than in the spleen of both control and resilient mice. Interestingly, NKG2D (natural killer group 2, member D) expression in the spleen of CSDS-susceptible mice was higher than that in control mice and CSDS-resilient mice. In addition, NKG2D expression in the spleen of patients with depression was higher than that in controls. Both increased splenic weight and increased splenic NKG2D expression in CSDS-susceptible mice were ameliorated after a subsequent administration of (R)-ketamine. The present findings indicate a novel role of splenic NKG2D in stress susceptibility versus resilience in mice subjected to CSDS. Furthermore, abnormalities in splenic functions in CSDS-susceptible mice were ameliorated after subsequent injection of (R)-ketamine. Thus, the brain–spleen axis might, at least in part, contribute to the pathogenesis of stress-related psychiatric disorders such as depression.

Downregulation of Serotonergic Gene Expression in the Raphe Nuclei of the Midbrain Under Chronic Social Defeat Stress in Male Mice

2013 ◽  
Vol 48 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Ul’yana A. Boyarskikh ◽  
Natalya P. Bondar ◽  
Maxim L. Filipenko ◽  
Natalia N. Kudryavtseva
Keyword(s):  
Gene Expression ◽  
Social Defeat ◽  
Raphe Nuclei ◽  
Male Mice ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress ◽  
Raphé Nuclei

scholarly journals Chronic social defeat stress impairs goal-directed behavior through dysregulation of ventral hippocampal activity in male mice

2021 ◽  
Author(s):  
Keitaro Yoshida ◽  
Michael R. Drew ◽  
Anna Kono ◽  
Masaru Mimura ◽  
Norio Takata ◽  
...  
Keyword(s):  
Social Withdrawal ◽  
Social Defeat ◽  
Task Completion ◽  
Male Mice ◽  
Social Defeat Stress ◽  
Motivated Behavior ◽  
Hippocampal Activity ◽  
Chronic Social Defeat Stress ◽  
Food Seeking ◽  
Goal Directed Behavior

AbstractChronic stress is a risk factor for a variety of psychiatric disorders, including depression. Although impairments to motivated behavior are a major symptom of clinical depression, little is known about the circuit mechanisms through which stress impairs motivation. Furthermore, research in animal models for depression has focused on impairments to hedonic aspects of motivation, whereas patient studies suggest that impairments to appetitive, goal-directed motivation contribute significantly to motivational impairments in depression. Here, we characterized goal-directed motivation in repeated social defeat stress (R-SDS), a well-established mouse model for depression in male mice. R-SDS impaired the ability to sustain and complete goal-directed behavior in a food-seeking operant lever-press task. Furthermore, stress-exposed mice segregated into susceptible and resilient subpopulations. Interestingly, susceptibility to stress-induced motivational impairments was unrelated to stress-induced social withdrawal, another prominent effect of R-SDS in mouse models. Based on evidence that ventral hippocampus (vHP) modulates sustainment of goal-directed behavior, we monitored vHP activity during the task using fiber photometry. Successful task completion was associated with suppression of ventral hippocampal neural activity. This suppression was diminished after R-SDS in stress-susceptible but not stress-resilient mice. The serotonin selective reuptake inhibitor (SSRI) escitalopram and ketamine both normalized vHP activity during the task and restored motivated behavior. Furthermore, optogenetic vHP inhibition was sufficient to restore motivated behavior after stress. These results identify vHP hyperactivity as a circuit mechanism of stress-induced impairments to goal-directed behavior and a putative biomarker that is sensitive to antidepressant treatments and that differentiates susceptible and resilient individuals.

Sign in / Sign up

Export Citation Format

Share Document