scholarly journals Prelimbic-amygdala overexcitability mediates trait vulnerability in a novel mouse model of acute social defeat stress

2020 ◽  
Author(s):  
Yael S. Grossman ◽  
Clementine Fillinger ◽  
Alessia Manganaro ◽  
George Voren ◽  
Rachel Waldman ◽  
...  
Keyword(s):  
Structure Function ◽  
Social Stress ◽  
Basolateral Amygdala ◽  
Control Level ◽  
Behavioral Responses ◽  
Social Defeat ◽  
Confocal Imaging ◽  
Spine Density ◽  
Male Mice ◽  
Social Defeat Stress

BACKGROUNDDepression is a debilitating neuropsychiatric disorder with 20% lifetime prevalence in the developed world but only approximately half of afflicted individuals respond to currently available therapies. While there is growing understanding of the neurobiological underpinnings of the depressed brain, much less is known about the preexisting circuitry leading to selective vulnerability versus resilience. Elucidating these networks could lead to novel preventative approaches.METHODSWe developed a model of acute social defeat stress (ASDS) that allows classification of male mice into “susceptible” (socially avoidant) versus “resilient” (expressing control-level social approach) one hour after exposure to six minutes of social stress. Using circuit tracing and high-resolution confocal imaging, we explored differences in activation and dendritic spine density and morphology in the prelimbic to basolateral amygdala (PL→BLA) circuit in resilient versus susceptible mice. To test the functional relevance of identified structure/function differences to divergent behavioral responses, we used an intersectional chemogenetic approach to inhibit the PL→BLA circuit during or prior to ASDS.RESULTSSusceptible mice had greater PL→BLA recruitment during ASDS and activated PL→BLA neurons from susceptible mice had more and larger mushroom spines compared to resilient mice. Inhibition of the PL→BLA circuit led to a population shift towards resilience.CONCLUSIONPreexisting PL→BLA structure/function differences mediate divergent behavioral responses to ASDS in male mice. These results support the PL→BLA circuit as a biomarker of trait vulnerability and potential target for prevention of stress-induced psychopathology.

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.”

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 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.

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 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 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 (R)-Ketamine Rapidly Ameliorates the Decreased Spine Density in the Medial Prefrontal Cortex and Hippocampus of Susceptible Mice After Chronic Social Defeat Stress

2019 ◽  
Vol 22 (10) ◽  
pp. 675-679 ◽  
Author(s):  
Jiancheng Zhang ◽  
Youge Qu ◽  
Lijia Chang ◽  
Yaoyu Pu ◽  
Kenji Hashimoto
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Single Injection ◽  
Social Defeat ◽  
Spine Density ◽  
Social Defeat Stress ◽  
Dendritic Spine Density ◽  
Antidepressant Effects ◽  
Chronic Social Defeat Stress ◽  
Medial Pfc

Abstract Background A recent study demonstrated that spine formation rates by ketamine in the prefrontal cortex (PFC) were not altered at 3–6 h following a single injection, but were markedly altered at 12–24 h. Here, we investigated the acute (3 h post-treatment) effects of (R)-ketamine in the decreased spine density in the medial PFC (mPFC) and hippocampus in susceptible mice after chronic social defeat stress (CSDS). Methods (R)-ketamine (10 mg/kg) or saline was administered intraperitoneally to CSDS-susceptible mice. Dendritic spine density in the mPFC and hippocampus was measured 3 h after a single injection. Results (R)-ketamine significantly ameliorated the decreased spine density in the prelimbic area of mPFC, Cornu Ammonis3, and dentate gyrus of the hippocampus of CSDS-susceptible mice Conclusions This study suggests that (R)-ketamine rapidly ameliorates the decreased spine density in the mPFC and hippocampus of CSDS-susceptible mice, resulting in its rapid-acting antidepressant effects.

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