Korean Red Ginseng reduces chronic social defeat stress-induced mood disorders via N-methyl-D-aspartate receptor modulation in mice

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.

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Korean Red Ginseng extract mitigates CSDS-induced mood disorders by modulating NMDA receptor

IBRO Reports ◽

10.1016/j.ibror.2019.07.775 ◽

2019 ◽

Vol 6 ◽

pp. S248-S249

Author(s):

Su-Jeong Sung ◽

Bo-Ram Lee ◽

Yong-Hyun Ko ◽

Seok-Yong Lee ◽

Choon-Gon Jang

Keyword(s):

Nmda Receptor ◽

Mood Disorders ◽

Red Ginseng ◽

Korean Red Ginseng ◽

Ginseng Extract ◽

Induced Mood

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Chronic social defeat stress: Impact on sleep in susceptible mice

10.26226/morressier.5971be85d462b80290b52711 ◽

2017 ◽

Author(s):

Fiona Henderson

Keyword(s):

Social Defeat ◽

Social Defeat Stress ◽

Chronic Social Defeat Stress

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Brain histamine and oleoylethanolamide restore behavioral deficits induced by chronic social defeat stress in mice

Neurobiology of Stress ◽

10.1016/j.ynstr.2021.100317 ◽

2021 ◽

pp. 100317

Author(s):

Barbara Rani ◽

Andrea Santangelo ◽

Adele Romano ◽

Justyna Barbara Koczwara ◽

Marzia Friuli ◽

...

Keyword(s):

Social Defeat ◽

Social Defeat Stress ◽

Behavioral Deficits ◽

Brain Histamine ◽

Chronic Social Defeat Stress

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

Translational Psychiatry ◽

10.1038/s41398-021-01250-9 ◽

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.

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Low-Molecular Weight BDNF Mimetic, Dimeric Dipeptide GSB-106, Reverses Depressive Symptoms in Mouse Chronic Social Defeat Stress

Biomolecules ◽

10.3390/biom11020252 ◽

2021 ◽

Vol 11 (2) ◽

pp. 252

Author(s):

Tatiana A. Gudasheva ◽

Anna V. Tallerova ◽

Armen G. Mezhlumyan ◽

Tatyana A. Antipova ◽

Ilya O. Logvinov ◽

...

Keyword(s):

Dose Range ◽

Social Defeat ◽

Social Defeat Stress ◽

In Vivo Experiments ◽

Trk Receptor ◽

Chronic Social Defeat Stress ◽

Swimming Test ◽

Scientific Group

A mimetic of the BDNF loop 4, bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, named GSB-106, was designed and synthesized in our scientific group. The compound activated TrkB, MAPK/ERK, PI3K/AKT, and PLCγ in in vitro experiments. In vivo experiments with rodents revealed its antidepressant-like activity in the forced swim and the tail suspension tests at the dose range of 0.1–5.0 mg/kg (i.p., p.o.). However, GSB-106 was not studied in depression models modulating major depression in humans. In the present study, the GSB-106 antidepressant-like activity was revealed in mice at the depression model induced by 28-day social defeat stress with 21-days oral administration (0.1 mg/kg) after stress. At the same time, GSB-106 restored reduced locomotor activity and completely eliminated the anhedonia manifestations. The compound also restored reduced levels of synaptophysin and CREB in the hippocampus. In addition, the Trk receptor antagonist K252A, and the PLC inhibitor U73122, were found to completely block the antidepressant-like activity of GSB-106 in the forced swimming test in mice. Thus, the present results demonstrate the dipeptide BDNF mimetic GSB-106 reversed depressive-like behavior and restored hippocampal neuroplasticity in a rodent depression model. These effects of GSB-106 are probably regulated by TrkB signaling.

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