scholarly journals Chronic non-discriminatory social defeat stress reduces effort-related motivated behaviors in male and female mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew Dieterich ◽  
Tonia Liu ◽  
Benjamin Adam Samuels
Keyword(s):  
Mood Disorders ◽  
Chronic Stress ◽  
Choice Behavior ◽  
Progressive Ratio ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
Male And Female ◽  
Female Mice ◽  
High Reward ◽  
Motivated Behaviors

AbstractReward and motivation deficits are prominent symptoms in many mood disorders, including depression. Similar reward and effort-related choice behavioral tasks can be used to study aspects of motivation in both rodents and humans. Chronic stress can precipitate mood disorders in humans and maladaptive reward and motivation behaviors in male rodents. However, while depression is more prevalent in women, there is relatively little known about whether chronic stress elicits maladaptive behaviors in female rodents in effort-related motivated tasks and whether there are any behavioral sex differences. Chronic nondiscriminatory social defeat stress (CNSDS) is a variation of chronic social defeat stress that is effective in both male and female mice. We hypothesized that CNSDS would reduce effort-related motivated and reward behaviors, including reducing sensitivity to a devalued outcome, reducing breakpoint in progressive ratio, and shifting effort-related choice behavior. Separate cohorts of adult male and female C57BL/6 J mice were divided into Control or CNSDS groups, exposed to the 10-day CNSDS paradigm, and then trained and tested in instrumental reward or effort-related behaviors. CNSDS reduced motivation to lever press in progressive ratio and shifted effort-related choice behavior from a high reward to a more easily attainable low reward in both sexes. CNSDS caused more nuanced impairments in outcome devaluation. Taken together, CNSDS induces maladaptive shifts in effort-related choice and reduces motivated lever pressing in both sexes.

scholarly journals Histone Lysine Demethylase JMJD2D/KDM4D and Family Members Mediate Effects of Chronic Social Defeat Stress on Mouse Hippocampal Neurogenesis and Mood Disorders

2020 ◽  
Vol 10 (11) ◽  
pp. 833
Author(s):  
Swati Maitra ◽  
Nitin Khandelwal ◽  
Scherazad Kootar ◽  
Pooja Sant ◽  
Salil S. Pathak ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Chronic Stress ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
Histone Lysine ◽  
Chronic Social Defeat Stress ◽  
Proliferation And Differentiation ◽  
Lysine Residues ◽  
Induced Changes

Depression, anxiety and related mood disorders are major psychiatric illnesses worldwide, and chronic stress appears to be one of the primary underlying causes. Therapeutics to treat these debilitating disorders without a relapse are limited due to the incomplete molecular understanding of their etiopathology. In addition to the well-studied genetic component, research in the past two decades has implicated diverse epigenetic mechanisms in mediating the negative effects of chronic stressful events on neural circuits. This includes the cognitive circuitry, where the dynamic hippocampal dentate gyrus (DG) neurogenesis gets affected in depression and related affective disorders. Most of these epigenetic studies have focused on the impact of acetylation/deacetylation and methylation of several histone lysine residues on neural gene expression. However, there is a dearth of investigation into the role of demethylation of these lysine residues in chronic stress-induced changes in neurogenesis that results in altered behaviour. Here, using the chronic social defeat stress (CSDS) paradigm to induce depression and anxiety in C57BL/6 mice and ex vivo DG neural stem/progenitor cell (NSCs/NPCs) culture we show the role of the members of the JMJD2/KDM4 family of histone lysine demethylases (KDMs) in mediating stress-induced changes in DG neurogenesis and mood disorders. The study suggests a critical role of JMJD2D in DG neurogenesis. Altered enrichment of JMJD2D on the promoters of Id2 (inhibitor of differentiation 2) and Sox2 (SRY-Box Transcription Factor 2) was observed during proliferation and differentiation of NSCs/NPCs obtained from the DG. This would affect the demethylation of repressive epigenetic mark H3K9, thus activating or repressing these and possibly other genes involved in regulating proliferation and differentiation of DG NSCs/NPCs. Treatment of the NSCs/NPCs culture with Dimethyloxallyl Glycine (DMOG), an inhibitor of JMJDs, led to attenuation in their proliferation capacity. Additionally, systemic administration of DMOG in mice for 10 days induced depression-like and anxiety-like phenotype without any stress exposure.

scholarly journals Stress-induced alterations of mesocortical and mesolimbic dopaminergic pathways

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
F. Quessy ◽  
T. Bittar ◽  
L. J. Blanchette ◽  
M. Lévesque ◽  
B. Labonté
Keyword(s):  
Molecular Interactions ◽  
Life Stress ◽  
Social Stress ◽  
Cognitive Strategies ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
Male And Female ◽  
Female Mice ◽  
Males And Females ◽  
Dopaminergic Pathways

AbstractOur ability to develop the cognitive strategies required to deal with daily-life stress is regulated by region-specific neuronal networks. Experimental evidence suggests that prolonged stress in mice induces depressive-like behaviors via morphological, functional and molecular changes affecting the mesolimbic and mesocortical dopaminergic pathways. Yet, the molecular interactions underlying these changes are still poorly understood, and whether they affect males and females similarly is unknown. Here, we used chronic social defeat stress (CSDS) to induce depressive-like behaviors in male and female mice. Density of the mesolimbic and mesocortical projections was assessed via immuno-histochemistry combined with Sholl analysis along with the staining of activity-dependent markers pERK and c-fos in the ventral tegmental area (VTA), nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). Our results show that social stress decreases the density of TH+ dopaminergic axonal projections in the deep layers of the mPFC in susceptible but not resilient male and female mice. Consistently, our analyses suggest that pERK expression is decreased in the mPFC but increased in the NAc following CSDS in males and females, with no change in c-fos expression in both sexes. Overall, our findings indicate that social defeat stress impacts the mesolimbic and mesocortical pathways by altering the molecular interactions regulating somatic and axonal plasticity in males and females.

scholarly journals Chronic non-discriminatory social defeat is an effective chronic stress paradigm for both male and female mice

2019 ◽  
Vol 44 (13) ◽  
pp. 2220-2229 ◽  
Author(s):  
Christine N. Yohn ◽  
Andrew Dieterich ◽  
Allyson S. Bazer ◽  
Isabella Maita ◽  
Megan Giedraitis ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Social Defeat ◽  
Male And Female ◽  
Female Mice

scholarly journals Vicarious Social Defeat Stress Induces Depression-Related Outcomes in Female Mice

2018 ◽  
Vol 83 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Sergio D. Iñiguez ◽  
Francisco J. Flores-Ramirez ◽  
Lace M. Riggs ◽  
Jason B. Alipio ◽  
Israel Garcia-Carachure ◽  
...  
Keyword(s):  
Social Defeat ◽  
Social Defeat Stress ◽  
Female Mice

scholarly journals Roles of multiple lipid mediators in stress and depression

2019 ◽  
Vol 31 (9) ◽  
pp. 579-587 ◽  
Author(s):  
Tomoyuki Furuyashiki ◽  
Satoshi Akiyama ◽  
Shiho Kitaoka
Keyword(s):  
Chronic Stress ◽  
Social Defeat ◽  
Lipid Mediators ◽  
Mental Illnesses ◽  
Lipid Mediator ◽  
Receptor Subtype ◽  
Social Defeat Stress ◽  
Beneficial Effects ◽  
Prostaglandin Synthase ◽  
Depressive Patients

AbstractProlonged or excessive stress may induce emotional and cognitive disturbances, and is a risk factor for mental illnesses. Using rodent chronic stress models of depression, roles of multiple lipid mediators related to inflammation have been revealed in chronic stress-induced emotional alterations. Prostaglandin (PG) E2, an arachidonic acid (AA)-derived lipid mediator, and its receptor subtype EP1 mediate depression-like behavior induced by repeated social defeat stress through attenuating prefrontal dopaminergic activity. Repeated social defeat stress activates microglia through innate immune receptors, and induces PGE2 synthesis through cyclooxygenase-1, a prostaglandin synthase enriched in microglia. PGD2, another AA-derived lipid mediator, has been implicated in depression induced by chronic stress, although either pro-depressive or anti-depressive actions have been reported. Chronic stress up-regulates hippocampal expression of 5-lipoxygenase, hence synthesis of cysteinyl leukotrienes, thereby inducing depression through their receptors. Consistent with beneficial effects of n-3 fatty acids in the diet of depressive patients, resolvins—a novel class of pro-resolving lipid mediators—in the brain attenuate neuroinflammation-associated depression. These findings in animal models of depression offer lipid mediators and related molecules as novel therapeutic targets for treating depression. To translate these findings into clinics, translational biomarkers to visualize lipid mediator profiles in depressive patients need to be established.

scholarly journals Social instability is an effective chronic stress paradigm for both male and female mice

2019 ◽  
Vol 160 ◽  
pp. 107780 ◽  
Author(s):  
Christine N. Yohn ◽  
Sandra A. Ashamalla ◽  
Leshya Bokka ◽  
Mark M. Gergues ◽  
Alexander Garino ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Male And Female ◽  
Social Instability ◽  
Female Mice

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.

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 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.

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