scholarly journals Toward Understanding the Sex Differences in the Biological Mechanism of Social Stress in Mouse Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Aki Takahashi
Keyword(s):  
Sex Differences ◽  
Social Stress ◽  
Social Defeat ◽  
Preclinical Studies ◽  
Biological Mechanism ◽  
Depression And Anxiety ◽  
Social Defeat Stress ◽  
Pharmacological Interventions ◽  
Recent Developments ◽  
Stress Models

Significant sex differences in terms of prevalence, symptomatic profiles, severity, and comorbidities of psychiatric disorders are quite common. Women have been shown to be more vulnerable to stress and are nearly twice as likely as men to develop stress-related disorders such as depression and anxiety. Therefore, understanding sex differences with respect to the neurobiological mechanisms underlying stress-related disorders is important for developing more efficient pharmacological interventions for women. However, most preclinical studies on stress-related disorders have focused heavily on male rodents. Here, recent developments in the study of repeated social defeat stress models in female mice are summarized. Our findings suggest that a variety of factors need to be considered when employing this model.

scholarly journals Ingestion of probiotic (Lactobacillus helveticus and Bifidobacterium longum) alters intestinal microbial structure and behavioral expression following social defeat stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katherine A. Partrick ◽  
Anna M. Rosenhauer ◽  
Jérémie Auger ◽  
Amanda R. Arnold ◽  
Nicole M. Ronczkowski ◽  
...  
Keyword(s):  
Social Stress ◽  
Bifidobacterium Longum ◽  
Social Defeat ◽  
Lactobacillus Helveticus ◽  
Rrna Gene ◽  
Social Avoidance ◽  
Social Defeat Stress ◽  
Microbial Structure ◽  
Microbial Composition ◽  
Anti Inflammatory

AbstractSocial stress exacerbates anxious and depressive behaviors in humans. Similarly, anxiety- and depressive-like behaviors are triggered by social stress in a variety of non-human animals. Here, we tested whether oral administration of the putative anxiolytic probiotic strains Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces the striking increase in anxiety-like behavior and changes in gut microbiota observed following social defeat stress in Syrian hamsters. We administered the probiotic at two different doses for 21 days, and 16S rRNA gene amplicon sequencing revealed a shift in microbial structure following probiotic administration at both doses, independently of stress. Probiotic administration at either dose increased anti-inflammatory cytokines IL-4, IL-5, and IL-10 compared to placebo. Surprisingly, probiotic administration at the low dose, equivalent to the one used in humans, significantly increased social avoidance and decreased social interaction. This behavioral change was associated with a reduction in microbial richness in this group. Together, these results demonstrate that probiotic administration alters gut microbial composition and may promote an anti-inflammatory profile but that these changes may not promote reductions in behavioral responses to social stress.

scholarly journals Unique effects of social defeat stress in adolescent male mice on the Netrin-1/DCC pathway, prefrontal cortex dopamine and cognition (Social stress in adolescent vs. adult male mice)

eNeuro ◽  
2021 ◽  
pp. ENEURO.0045-21.2021
Author(s):  
Philip Vassilev ◽  
Andrea Haree Pantoja-Urban ◽  
Michel Giroux ◽  
Dominique Nouel ◽  
Giovanni Hernandez ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Adult Male ◽  
Social Stress ◽  
Social Defeat ◽  
Adolescent Male ◽  
Male Mice ◽  
Social Defeat 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 Sex Differences in Social Interaction Behavior Following Social Defeat Stress in the Monogamous California Mouse (Peromyscus californicus)

PLoS ONE ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. e17405 ◽  
Author(s):  
Brian C. Trainor ◽  
Michael C. Pride ◽  
Rosalina Villalon Landeros ◽  
Nicholas W. Knoblauch ◽  
Elizabeth Y. Takahashi ◽  
...  
Keyword(s):  
Sex Differences ◽  
Social Interaction ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
Peromyscus Californicus ◽  
Interaction Behavior

Blockade of D3 receptor prevents changes in DAT and D3R expression in the mesolimbic dopaminergic circuit produced by social stress- and cocaine prime-induced reinstatement of cocaine-CPP

2020 ◽  
Vol 34 (11) ◽  
pp. 1300-1315
Author(s):  
Rocío Guerrero-Bautista ◽  
Aurelio Franco-García ◽  
Juana M Hidalgo ◽  
Francisco Fernández-Gómez ◽  
M Victoria Milanés ◽  
...  
Keyword(s):  
Social Stress ◽  
Social Defeat ◽  
Behavioral Effects ◽  
The Other ◽  
D3 Receptor ◽  
Male Mice ◽  
Social Defeat Stress ◽  
Priming Dose ◽  
The Impact ◽  
The Brain

Background: Cocaine may cause persistent changes in the brain, which are more apparent in DA transporter (DAT) and DA receptor availability within the nucleus accumbens (NAc). On the other hand, the DA D3 receptor (D3R) has emerged as a promising pharmacotherapeutic target for substance use disorders. Aims: This study aims to assess the impact of selective D3R antagonism on DAT and D3R after reinstatement of cocaine preference (CPP) induced by an acute session of social defeat stress (SDS) and a cocaine prime in mice after a period of abstinence. Methods: Male mice were conditioned with 25 mg/kg of cocaine for 4 days. After 60 days of extinction training mice were pretreated with the selective D3R antagonist SB-277011A before the re-exposure to a priming dose of cocaine or to a single SDS session. CPP scores were determined and levels of DAT, D3R, phospho Akt (pAkt) and phospho mTOR (pmTOR) were assessed in the NAc shell. Results: An increase in DAT and D3R expression was seen in the NAc after both a cocaine prime- and SDS-induced reinstatement of CPP. Pretreatment with SB-277011A blocked elevated DAT and D3R expression as well as SDS-induced reinstatement. By contrast, the blockade of D3R did not modified the cocaine prime-induced CPP. Changes in DAT and D3R expression do not seem to occur via the canonic pathway involving Akt/mTOR. Conclusions: Our results suggest that the selective D3R antagonist ability to inhibit DAT and D3R up-regulation could represent a possible mechanism for its behavioral effects in cocaine-memories reinstatement induced by social stress.

scholarly journals Stress-induced sleep-like inactivity modulates stress susceptibility in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Midori Nagai ◽  
Hirotaka Nagai ◽  
Chisato Numa ◽  
Tomoyuki Furuyashiki
Keyword(s):  
Sleep Deprivation ◽  
Social Stress ◽  
Social Interest ◽  
Social Behaviors ◽  
Social Defeat ◽  
Brain Regions ◽  
Social Characteristics ◽  
Social Avoidance ◽  
Social Defeat Stress ◽  
Positive Valence

AbstractSevere environmental and social stress induces dysregulation of sleep along with mood and cognitive disturbances. However, the role and mechanism of this sleep dysregulation remain elusive. Here we evaluated sleep-like inactivity measured by voluntary movements and its relationship to social behaviors in mice without or with social defeat stress as well as the stressed mice with subsequent sleep deprivation. Social defeat stress immediately induced sleep-like inactivity with decreased body temperature. In the social interaction test, the control mice showed high social interest and its correlation with social sniffing intensity, the latter of which indicates positive valence of social sniffing. After the stress, these social characteristics were maintained in stress-resilient mice, but disrupted in stress-susceptible mice, leading to social avoidance. Sleep deprivation after the stress decreased social sniffing intensity along with reduced social interest, but enhanced the exploratory activity with the positive valence of social sniffing. We also found by c-Fos immunohistochemistry that the stress activated sleep-related brain regions, the dorsomedial hypothalamus and ventrolateral periaqueductal gray. Collectively, these findings show that stress activates sleep-related brain regions and induces sleep-like inactivity, contributing to multiple roles of stress-induced sleep for social behaviors.

scholarly journals Sex-Dependent Effects of Chronic Social Defeat on Emotional and Social Behaviors, and Parameters of Oxytocin and Vasopressin Systems in Mandarin Voles (Microtus mandarinus)

2021 ◽  
Vol 15 ◽  
Author(s):  
Wenjuan Hou ◽  
Huan Ma ◽  
Yufeng Xun ◽  
Xin Zhang ◽  
Wenqi Cai ◽  
...  
Keyword(s):  
Sex Differences ◽  
Open Field ◽  
Social Stress ◽  
Social Withdrawal ◽  
Forced Swim Test ◽  
Central Area ◽  
Social Behaviors ◽  
Tail Suspension Test ◽  
Social Defeat ◽  
Double Labeling

In the regulation of emotional and social behaviors, both oxytocin (OT) and vasopressin (AVP) are sex specific. Although significant sex differences have been reported in the context of behavioral and hormonal responses to social stress, such differences in response to chronic social defeat stress (CSDS) and the underlying neural mechanisms remain largely unknown. By investigating monogamous mandarin voles (Microtus mandarinus), CSDS was found to decrease the percentages of time spent in the central area of the open field, in the open arms of the elevated plus maze, as well as in the light area of the light and dark boxes in both male and female voles. CSDS also increased the observed level of social withdrawal in both sex groups. However, CSDS exposure increased the percentages of immobile time in both the tail suspension test and the forced swim test and reduced the locomotor activity in the open field (in females only). Along with these behavioral changes, the oxytocin receptor (OTR) levels in the nucleus accumbens (NAc) were significantly lower in CSDS-exposed voles of both sexes; however, in males, the levels of OTR in the paraventricular nucleus (PVN) were reduced. CSDS-exposed males showed lower levels of V1aR in the NAc than CSDS-exposed females. Furthermore, induced by a single social defeat event, CSDS reduced c-Fos and OT double labeling in the PVN of females but increased c-Fos and AVP double-labeled neurons in the PVN of males exposed to a single social defeat event. Collectively, the present study indicates that OT and AVP systems may play important regulatory roles in the sex differences of behavioral performances in response to CSDS. These findings suggest mandarin voles as a useful animal model for studying sex-specific behavioral performance and the underlying neurobiological mechanisms of stress-related mental disorders in preclinical studies.

scholarly journals 510 - EFFECT OF SLEEP DEPRIVATION ON SOCIAL RESILIENCE THROUGH ΔFOSB ACTIVATION

2021 ◽  
Vol 33 (S1) ◽  
pp. 61-62
Author(s):  
Neha Gregory ◽  
Eva Andrews ◽  
Caroline Donnay ◽  
Darielle Lewis-Sanders ◽  
Tayler Arnold ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Social Stress ◽  
Social Defeat ◽  
Depression And Anxiety ◽  
Social Resilience ◽  
Geriatric Population ◽  
Senior Population ◽  
Neurochemical Changes ◽  
The Brain ◽  
Chronic Sleep

Introduction:Stress can have a variety of detrimental effects on humans. From depression and anxiety to schizophrenia, stress plays a factor in the development of these diseases through neurochemical changes in the brain and elevated levels of hormones. Among the geriatric population, decreased sleep levels are known to be a frequent issue; insomnia rates among the senior population are much higher in frequency compared to any other age group. Sleep deprivation also leads to major consequences in the brain and sleep disruption is linked to neuropsychological illness; however, the specific mechanisms involved in these effects are not understood. This study focuses on the resilient effects of ΔFosB, a protein known to mediate resilience to stress and the direct effect of sleep deprivation on ΔFosB expression in areas known to mediate resilience to social stress. We hypothesize that ΔFosB may be part of the mechanism through which sleep alters resilience to social stress.Methods:Mice were sleep-deprived for an eight-hour period for five days. After sleep deprivation they were subject to social defeat and underwent avoidance testing. The brains of these mice were removed, and immunohistochemistry analysis was conducted to determine ∆FosB expression in various sections of the brain.Results:The preliminary findings of this study indicates that sleep is altered in resilient animals and that sleep deprivation may lead to increased resilience to social defeat. The most significant decrease in ∆FosB expression was found in the prelimbic cortex, a change associated with resilience, and which was observed after chronic sleep deprivation. Contrarily, there was also an increase of ∆FosB expression in the nucleus accumbens.Conclusion:These findings indicate that changes in ∆FosB activation in the brain is a significant factor for promoting resilient behavior in situations of social stress. In particular, a decrease in ∆FosB activation in the PLC plays a role in explaining how sleep deprivation contributes to decreased social resilience in situations of social stress.

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.

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