Chronic stress-induced changes in the rat brain: Role of sex differences and effects of long-term tianeptine treatment

2013 ◽  
Vol 75 ◽  
pp. 426-436 ◽  
Author(s):  
Sjoukje D. Kuipers ◽  
Andrea Trentani ◽  
Eddy A. van der Zee ◽  
Johan A. den Boer
Keyword(s):  
Sex Differences ◽  
Rat Brain ◽  
Chronic Stress ◽  
Induced Changes

scholarly journals Flavonoids Ameliorate Stress-Induced Depression by Preventing NLRP3 Inflammasome Priming

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1231-1231
Author(s):  
Giulio Pasinetti
Keyword(s):  
Mrna Expression ◽  
Chronic Stress ◽  
Nlrp3 Inflammasome ◽  
Signaling Cascades ◽  
Dietary Polyphenols ◽  
Funding Sources ◽  
Glycation End Products ◽  
Molecular Patterns

Abstract Objectives Chronic stress activates danger-associated molecular patterns (DAMPs), stimulating the NLRP3 inflammasome. NLRP3 activation triggers the release of pro-inflammatory cytokine IL-1β. The activity of the NLRP3 inflammasome propagates pro-inflammatory signaling cascades implicated in the onset of depression. Our previous studies show that polyphenolic compounds were found to ameliorate stress induced depression in mouse models. However, the relevant mechanism has not been identified. This study examined the effect of administering polyphenols on DAMP signaling in enriched mice microglia. Methods This study examined the effect of administering polyphenols on DAMP signaling in mice microglia. To recapitulate stress-induced depression, mice underwent chronic unpredictable stress (CUS). Microglia were isolated at various time points throughout the CUS protocol. We also assessed long-term persistent changes after CUS and susceptibility to subthreshold unpredictable stress (US) re-exposure. Results Interestingly, the development of US – induced depression and anxiety depended upon a previous exposure to CUS. We found that CUS caused robust upregulation of IL-1β mRNA in enriched microglia, an effect that persists for up to 4 weeks following CUS exposure. Following the subthreshold US re-exposure, we observed the upregulation of pro- IL-1β as well as pro-receptor for advanced glycation end products (RAGE). Toll-like receptor 4 (TLR-4) was not. We also observed an increase in RAGE mRNA expression when mice were exposed to US prior to the start of the CUS paradigm. Importantly, a primary exposure to US, was sufficient to increase RAGE mRNA expression. We found that polyphenol administration significantly improved CUS-induced depressive-like phenotypes and also reversed neuroinflammation in mice. Treatment with dietary flavonoids prevented upregulation of IL-1β, RAGE mRNA, which reflects the ability of polyphenols that may have begun following the primary exposure to US. Conclusions Taken all together, the results provide evidence of the role of dietary polyphenols in preventing persistent microglial activation, which has been shown to result in reduced long term vulnerability to depressive-like behaviors following expose to chronic stress. Funding Sources This study was supported by a P50 CARBON Center grant from the NCCIH/ODS.

scholarly journals Role of the modulation of Nkb pathway in chronic stress induced changes in the BNST and consequences on the anxiety behavior

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S78
Author(s):  
Aurelie Menigoz ◽  
Donald Rainnie ◽  
Katie Barrett ◽  
Megan Jiang ◽  
Larry Young
Keyword(s):  
Chronic Stress ◽  
Anxiety Behavior ◽  
Induced Changes

scholarly journals Sex differences in chronic social stress models in mice

2019 ◽  
Author(s):  
Orit Furman ◽  
Michael Tsoory ◽  
Alon Chen
Keyword(s):  
Sex Differences ◽  
Animal Models ◽  
Mouse Model ◽  
Treatment Response ◽  
Chronic Stress ◽  
Social Stress ◽  
Molecular Mechanisms ◽  
Body Weight Loss ◽  
Chronic Social Stress

AbstractChronic stress creates an allostatic overload that may lead to mood disorders such as anxiety and depression. Modern causes of chronic stress in humans are mostly social in nature, relating to work and relationship stress. Research into neural and molecular mechanisms of vulnerability and resilience following chronic social stress (CSS) is ongoing and uses animal models to discover efficient prevention strategies and treatments. To date, most CSS studies have neglected the female sex and used male-focused aggression-based animal models such as chronic social defeat stress (CSDS). Accumulating evidence on sex differences suggests differences in the stress response, the prevalence of stress-related illness and the treatment response, indicating that researchers should expand CSS investigation to include female-focused protocols alongside the popular CSDS protocols. Here, we describe a novel female mouse model of CSS and a parallel modified male mouse model of CSDS in C57BL/6 mice. These new models enable the investigation of vulnerability, coping and downstream effectors mediating long-term consequences of CSS in both sexes. Our data demonstrate sex differences during CSS and for many weeks following CSS. Female mice are more prone to body weight loss during CSS and hyperactive anxious behavior following CSS. Both sexes show disturbances in social interaction, but only stressed male mice show long-term changes in neuroendocrine function and memory performance after fear conditioning. We discuss future avenues of research using these models to investigate mechanisms pertaining to sensitivity to CSS as well as treatment response profiles, in a sex-suitable manner.

Long-term adjustment of hepatic lipid metabolism after chronic stress and the role of FGF21

2022 ◽  
Vol 1868 (1) ◽  
pp. 166286
Author(s):  
Matthias Dille ◽  
Aleksandra Nikolic ◽  
Natalie Wahlers ◽  
Pia Fahlbusch ◽  
Sylvia Jacob ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Chronic Stress ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

scholarly journals Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats

2008 ◽  
Vol 19 (9) ◽  
pp. 1978-1989 ◽  
Author(s):  
Y. Lin ◽  
G. J. Ter Horst ◽  
R. Wichmann ◽  
P. Bakker ◽  
A. Liu ◽  
...  
Keyword(s):  
Sex Differences ◽  
Chronic Stress ◽  
Brain Regions ◽  
Acute And Chronic Stress

scholarly journals PRIMING OF MICROGLIA ACTIVITY INCREASES SUSCEPTIBILITY TO DEPRESSION-LIKE BEHAVIORS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S95-S95
Author(s):  
Tal Frolinger ◽  
Umar Iqbal ◽  
Giulio M Pasinetti
Keyword(s):  
Gene Expression ◽  
Depression And Anxiety ◽  
Toll Like Receptor 4 ◽  
Immune Priming ◽  
Symptoms Of Depression ◽  
Tlr4 Gene ◽  
Induced Changes ◽  
Increased Activity

Abstract This study investigates the role of microglia activity in stress-induced depression and anxiety and the mechanisms associated with the role of certain microbiome derived anti-inflammatory polyphenols in attenuating stress-induced microglia immune priming and symptoms of depression. We implemented a chronic unpredictable stress (CUS) paradigm to exhibit priming of microglia innate immunity in the context of the onset of depression and anxiety phenotypes. Mechanistic studies related to prophylactic treatment using dietary microbiome derived polyphenols were also investigated in this model. Depression and anxiety phenotypes, gene expression in microglia and protein expression in the cortex of mice were measured following a primary exposure to short-term unpredictable stress (US) followed by CUS. We examined the long-term, persistent CUS induced changes at 4-weeks of post-stress rest following a secondary US exposure. We found depression phenotypes resulted from US only following exposure to CUS. This was accompanied by an increase and persistent upregulation of toll-like receptor 4 (TLR4), RAGE, and HMGB1 gene expression in isolated cortical microglia. Priming by CUS also amplified gene expression of IL-1β in microglia and protein IL-1β in the cerebral cortex following US re-exposure. Increased activity of NF-kB was also noted in the period following CUS. Furthermore, polyphenol treatment prevented stress-induced phenotypes, upregulation of HMGB1, IL-1B, and TLR4 gene expression, as well as upregulation of IL-1β and NF-kB. The study suggests that latent activity of the TLR4-NFkB-IL1β pathway contributes to immune priming and increases susceptibility to depression-like behaviors. Anti-depressant effects of polyphenols may result from their ability to attenuate microglia priming.

scholarly journals Polyphenolic Compounds Ameliorate Stress-induced Depression by Preventing NLRP3 Inflammasome Priming (P19-011-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tal Frolinger ◽  
Giulio Pasinetti
Keyword(s):  
Mrna Expression ◽  
Chronic Stress ◽  
Nlrp3 Inflammasome ◽  
Polyphenolic Compounds ◽  
Dietary Polyphenols ◽  
Funding Sources ◽  
Glycation End Products ◽  
Molecular Patterns

Abstract Objectives Chronic stress activates danger-associated molecular patterns (DAMPs), which then stimulate the NLRP3 inflammasome. NLRP3 activation triggers the released of the pro-inflammatory cytokine IL‐1β.The activity of the NLRP3 inflammasome propagates pro-inflammatory signaling cascades implicated in the onset of depression. In previous studies conducted in our lab, polyphenolic compounds were found to ameliorate stress induced depression in mouse models. However, the mechanism by which they do so has not been identified. This study examined the effect of administering polyphenols on DAMP signaling in enriched mice microglia. Methods This study examined the effect of administering polyphenols on DAMP signaling in mice microglia. To recapitulate stress-induced depression, mice underwent chronic unpredictable stress (CUS). Microglia were isolated at various time points throughout the CUS protocol. We also assessed long-term persistent changes after CUS and susceptibility to subthreshold unpredictable stress (US) re-exposure. Results Interestingly, the development of US - induced depression and anxiety depended upon a previous exposure to CUS. We found that CUS caused robust upregulation of IL-1β mRNA in enriched microglia, an effect that persists for up to 4 weeks following CUS exposure. Following the subthreshold US re-exposure, we observed the upregulation of pro- IL-1β as well as pro-receptor for advanced glycation end products (RAGE). Toll-like receptor 4 (TLR-4) was not. We also observed an increase in RAGE mRNA expression when mice were exposed to US prior to the start of the CUS paradigm. Importantly, a primary exposure to US, was sufficient to increase RAGE mRNA expression. We found that polyphenol administration improved CUS-induced depressive-like phenotypes and also reversed neuroinflammation in mice. Treatment with dietary polyphenols prevented upregulation of IL-1β, RAGE mRNA, which reflects the ability of polyphenols that may have begun following the primary exposure to US. Conclusions Taken all together, the results provide evidence of the role of polyphenols in preventing persistent microglial activation, which has been shown to result in reduced long term vulnerability to depressive-like behaviors following expose to chronic stress. Funding Sources This study was supported by a P50 CARBON Center grant from the NCCIH and ODS.

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 Aerosol Induced Changes in Sea Surface Temperature Over the Bay of Bengal Due to COVID-19 Lockdown

2021 ◽  
Vol 8 ◽  
Author(s):  
T. S. Sarin ◽  
V. Vinoj ◽  
D. Swain ◽  
K. Landu ◽  
E. Suhas
Keyword(s):  
Surface Temperature ◽  
Sea Surface Temperature ◽  
Atmospheric Aerosols ◽  
Bay Of Bengal ◽  
Anthropogenic Activities ◽  
Sea Surface ◽  
Emissions Reduction ◽  
Induced Changes

The role of COVID-19 pandemic lockdown in improving air quality was reported extensively for land regions globally. However, limited studies have explored these over oceanic areas close to high anthropogenic activities and emissions. The Bay of Bengal (BoB) basin is one such region adjacent to the highly populated South Asian region. We find that Aerosol Optical Depth (AOD) over the BoB declined by as much as 0.1 or 30% during the peak lockdown of April 2020 compared to long-term climatology during 2003–2019. Simultaneously, the sea surface temperature (SST) rose by 0.5–1.5°C over the central and north-western parts of the BoB with an average increase of 0.83°C. We show that up to 30% of this observed warming is attributable to reduced atmospheric aerosols. The study highlights the importance of anthropogenic emissions reduction due to COVID lockdown on short-term changes to SST over ocean basins with implications to regional weather.

Sign in / Sign up

Export Citation Format

Share Document