Resilience

2020 ◽  
pp. 465-496
Author(s):  
Richard McCarty
Keyword(s):  
Immune System ◽  
Social Defeat ◽  
Behavioral Effects ◽  
Consistent Finding ◽  
Animal Models Of Depression ◽  
Chronic Social Defeat Stress ◽  
Stressful Stimulation ◽  
Related Line ◽  
Traumatic Stressors ◽  
The Brain

A consistent finding from research on animal models of depression and PTSD is that some animals are highly susceptible to the effects of stressful stimulation, while others show few obvious effects. A relatively new of line of research on resilience has emerged and has directed attention to those animals that are resistant to the effects of chronic or traumatic stressors. By tracking animals that are resistant to the behavioral effects of these stressful paradigms, one can then explore the molecular underpinnings of resilience in the brains of these same animals. Using chronic social defeat stress, some investigators have focused their attention on the ventral tegmental area, nucleus accumbens, and the prefrontal cortex. Other systems that have been studied include signaling molecules of the immune system and communication pathways between the immune system and the brain. A related line of research has addressed the possibility that prior exposure to stressors may inoculate animals to the deleterious effects of later stressor exposure.

Stress and Depression

2020 ◽  
pp. 365-394
Author(s):  
Richard McCarty
Keyword(s):  
Animal Models ◽  
Learned Helplessness ◽  
Inbred Mice ◽  
Social Defeat ◽  
Global Burden ◽  
Mild Stress ◽  
Animal Models Of Depression ◽  
Chronic Social Defeat Stress ◽  
Dopamine Circuits ◽  
The Brain

Major depressive disorder is a significant contributor to the global burden of disease, and it appears to be a mental disorder that is strongly dependent upon exposure to stressful stimuli. A major concern related to the development of animal models of depression is to capture those variables that explain the much higher incidence of depression in human females compared to males. Several genetically selected animal models have been studied, including the Flinders sensitive strain and the WKY strain. In addition, a strain of rats has been selected that is highly susceptible to the development of learned helplessness. Two especially valuable animal models of depression involve exposure of inbred mice to chronic social defeat stress (CSDS) or to chronic unpredictable mild stress. Results from these animal models point to disruptions in dopamine circuits in the brain as critical for the expression of depressive symptoms.

scholarly journals Brain type I but not type II IL-1 receptors mediate the effects of IL-1β on behavior in mice

1998 ◽  
Vol 274 (3) ◽  
pp. R735-R740 ◽  
Author(s):  
Sandrine Cremona ◽  
Emmanuelle Goujon ◽  
Keith W. Kelley ◽  
Robert Dantzer ◽  
Patricia Parnet
Keyword(s):  
Monoclonal Antibody ◽  
Immune System ◽  
Behavioral Response ◽  
Behavioral Effect ◽  
Behavioral Effects ◽  
Type I ◽  
Type Ii ◽  
Social Exploration ◽  
Neutralizing Monoclonal Antibody ◽  
The Brain

In the immune system, interleukin (IL)-1β effects are mediated by the type I IL-1 receptors (IL-1RI), whereas the type II IL-1 receptors (IL-1RII) act as inhibitory receptors. IL-1RI and IL-1RII are also present in the brain. To study their functionality in the brain, mice were centrally treated with neutralizing monoclonal antibody (MAb) directed against IL-1RI (35F5, 1 μg) or against IL-1RII (4E2, 2 μg) and were centrally injected with recombinant rat IL-1β at a dose (2 ng) that decreased social exploration. Only 35F5 was effective in abrogating the behavioral effect of IL-1β. Moreover, 4E2 (1 μg icv) did not potentiate the behavioral response to a subthreshold dose of IL-1β (1 ng icv). To examine the ability of brain IL-1RI to mediate the effects of endogenous IL-1β, mice were centrally treated with 35F5 (4 μg) and peripherally injected with IL-1β (1 μg). Like IL-1 receptor antagonist (4 μg icv), 35F5 abrogated the effects of IL-1β. These results suggest that brain IL-1RI mediates the behavioral effects of IL-1β in mice.

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 Cannabinoid receptor 1 signalling modulates stress susceptibility and microglial responses to chronic social defeat stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eva C. Beins ◽  
Thomas Beiert ◽  
Imke Jenniches ◽  
Jan N. Hansen ◽  
Este Leidmaa ◽  
...  
Keyword(s):  
Stress Responses ◽  
Cannabinoid Receptor ◽  
Inflammatory Responses ◽  
Myeloid Cells ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
Cannabinoid Receptor 1 ◽  
Behavioural Phenotype ◽  
Chronic Social Defeat Stress ◽  
The Brain

AbstractPsychosocial stress is one of the main environmental factors contributing to the development of psychiatric disorders. In humans and rodents, chronic stress is associated with elevated inflammatory responses, indicated by increased numbers of circulating myeloid cells and activation of microglia, the brain-resident immune cells. The endocannabinoid system (ECS) regulates neuronal and endocrine stress responses via the cannabinoid receptor 1 (CB1). CB1-deficient mice (Cnr1−/−) are highly sensitive to stress, but if this involves altered inflammatory responses is not known. To test this, we exposed Cnr1+/+ and Cnr1−/− mice to chronic social defeat stress (CSDS). Cnr1−/− mice were extremely sensitive to a standard protocol of CSDS, indicated by an increased mortality rate. Therefore, a mild CSDS protocol was established, which still induced a behavioural phenotype in susceptible Cnr1−/− mice. These mice also showed altered glucocorticoid levels after mild CSDS, suggesting dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. Mild CSDS induced weak myelopoiesis in the periphery, but no recruitment of myeloid cells to the brain. In contrast, mild CSDS altered microglial activation marker expression and morphology in Cnr1−/− mice. These microglial changes correlated with the severity of the behavioural phenotype. Furthermore, microglia of Cnr1−/− mice showed increased expression of Fkbp5, an important regulator of glucocorticoid signalling. Overall, the results confirm that CB1 signalling protects the organism from the physical and emotional harm of social stress and implicate endocannabinoid-mediated modulation of microglia in the development of stress-related pathologies.

Regional differences in dendritic spine density confer resilience to chronic social defeat stress

2017 ◽  
Vol 30 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Youge Qu ◽  
Chun Yang ◽  
Qian Ren ◽  
Min Ma ◽  
Chao Dong ◽  
...  
Keyword(s):  
Dendritic Spine ◽  
Regional Differences ◽  
Social Defeat ◽  
Brain Regions ◽  
Control Group ◽  
Spine Density ◽  
Dendritic Spine Density ◽  
Chronic Social Defeat Stress ◽  
The Brain ◽  
Susceptible Group

ObjectiveAlthough alterations in the dendritic spine density in the brain regions may play a role in the stress-induced depression-like phenotype, the precise mechanisms are unknown. The aim was to investigate the role of spine density in the brain regions after chronic social defeat stress (CSDS).MethodsWe examined dendritic spine density in the medial prefrontal cortex (mPFC), CA1, CA3, dentate gyrus (DG) of hippocampus, nucleus accumbens (NAc), and ventral tegmental area (VTA) of susceptible and resilient mice after CSDS.ResultsSpine density in the prelimbic area of mPFC, CA3, and DG in the susceptible group, but not resilient group, was significantly lower than control group. In contrast, spine density in the NAc and VTA in the susceptible group, but not resilient group, was significantly higher than control group.ConclusionsThe results suggest that regional differences in spine density may contribute to resilience versus susceptibility in mice subjected to CSDS.

scholarly journals Transcriptome-Wide Identification of G-to-A RNA Editing in Chronic Social Defeat Stress Mouse Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Ji Tao ◽  
Chun-Yan Ren ◽  
Zhi-Yuan Wei ◽  
Fuquan Zhang ◽  
Jinyu Xu ◽  
...  
Keyword(s):  
Rna Editing ◽  
Mouse Models ◽  
Physiological Stress ◽  
Neurological Diseases ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress ◽  
Solute Carrier ◽  
The Brain

Emerging evidence suggests that RNA editing is associated with stress, neurological diseases, and psychiatric disorders. However, the role of G-to-A RNA editing in chronic social defeat stress (CSDS) remains unclear. We herein identified G-to-A RNA editing and its changes in the ventral tegmental area (VTA), a key region of the brain reward system, in CSDS mouse models under emotional stress (ES) and physiological stress (PS) conditions. Our results revealed 3812 high-confidence G-to-A editing events. Among them, 56 events were significantly downregulated while 23 significantly upregulated in CSDS compared to controls. Moreover, divergent editing patterns were observed between CSDS mice under ES and PS conditions, with 42 and 21 events significantly upregulated in PS and ES, respectively. Interestingly, differential RNA editing was enriched in genes with multiple editing events. Genes differentially edited in CSDS included those genetically associated with mental or neurodevelopmental disorders, especially mood disorders, such as FAT atypical cadherin 1 and solute carrier family 6 member 1. Notably, changes of G-to-A RNA editing were also implicated in ionotropic glutamate receptors, a group of well-known targets of adenosine-to-inosine RNA editing. Such results demonstrate dynamic G-to-A RNA editing changes in the brain of CSDS mouse models, underlining its role as a potential molecular mechanism of CSDS and stress-related diseases.

scholarly journals Sex-specific retinal anomalies induced by chronic social stress in mice

2020 ◽  
Author(s):  
E Arsenault ◽  
AA Lavigne ◽  
S Mansouri ◽  
K Francis ◽  
TP Bittar ◽  
...  
Keyword(s):  
Stress Response ◽  
Social Stress ◽  
Social Defeat ◽  
Major Depressive ◽  
Male And Female ◽  
Retinal Activity ◽  
Female Mice ◽  
Chronic Social Defeat Stress ◽  
Before And After ◽  
The Brain

AbstractMajor depressive disorder (MDD) is one of the most common consequences of chronic stress. Still, there is currently no reliable biomarker to detect individuals at risk to develop MDD. Recently, the retina emerged as an effective way to approach the brain and investigate psychiatric disorders with the use of the electroretinogram (ERG). In this study, cones and rods ERGs were performed in male and female mice before and after chronic social defeat stress (CSDS). Mice were then divided as susceptible or resilient to stress. Significant results were only observed in rods ERGs. In males, susceptible mice showed prolonged a-wave implicit times at baseline that were shortened after CSDS. The a-wave was also decreased in both susceptible and resilient male mice after CSDS. In females, rod a-waves were shorter in susceptible than in control mice after CSDS resulting from the latter demonstrating delayed a-waves. Baseline ERGs were able to predict – to some extent – the expression of susceptibility and resilience before stress exposition in male and female mice. Overall, our findings suggest that retinal activity is a presumptive biomarker of stress response and that the ERG could potentially serve as a predicting tool of the stress response in mice.

scholarly journals Innate immune stimulation by monophosphoryl lipid A prevents chronic social defeat stress-induced anxiety-like behaviors in mice

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Fu Li ◽  
Haitao Xiang ◽  
Yue Gu ◽  
Ting Ye ◽  
Xu Lu ◽  
...  
Keyword(s):  
Lipid A ◽  
Social Defeat ◽  
Innate Immune ◽  
Stress Exposure ◽  
Preventive Effect ◽  
Social Defeat Stress ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Chronic Social Defeat Stress ◽  
The Brain

Abstract Background Innate immune pre-stimulation can prevent the development of depression-like behaviors in chronically stressed mice; however, whether the same stimulation prevents the development of anxiety-like behaviors in animals remains unclear. We addressed this issue using monophosphoryl lipid A (MPL), a derivative of lipopolysaccharide (LPS) that lacks undesirable properties of LPS but still keeps immune-enhancing activities. Methods The experimental mice were pre-injected intraperitoneally with MPL before stress exposure. Depression was induced through chronic social defeat stress (CSDS). Behavioral tests were conducted to identify anxiety-like behaviors. Real-time polymerase chain reaction (PCR) and biochemical assays were employed to examine the gene and protein expression levels of pro-inflammatory markers. Results A single MPL injection at the dose of 400 and 800 μg/kg 1 day before stress exposure prevented CSDS-induced anxiety-like behaviors, and a single MPL injection (400 μg/kg) five but not 10 days before stress exposure produced similar effect. The preventive effect of MPL on anxiety-like behaviors was also observed in CSDS mice who received a second MPL injection 10 days after the first MPL injection or a 4 × MPL injection 10 days before stress exposure. MPL pre-injection also prevented the production of pro-inflammatory cytokines in the hippocampus and medial prefrontal cortex in CSDS mice, and inhibiting the central immune response by minocycline pretreatment abrogated the preventive effect of MPL on CSDS-induced anxiety-like behaviors and pro-inflammatory cytokine productions in the brain. Conclusions Pre-stimulation of the innate immune system by MPL can prevent chronic stress-induced anxiety-like behaviors and neuroinflammatory responses in the brain in mice.

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