scholarly journals Taurine Alleviates Chronic Social Defeat Stress-Induced Depression by Protecting Cortical Neurons from Dendritic Spine Loss

2021 ◽  
Author(s):  
Yuanyuan Zhu ◽  
Rui Wang ◽  
Ze Fan ◽  
Danlei Luo ◽  
Guohong Cai ◽  
...  
Keyword(s):  
Amino Acid ◽  
Dendritic Spine ◽  
Cortical Neurons ◽  
Extracellular Fluid ◽  
Social Defeat ◽  
Social Avoidance ◽  
Social Defeat Stress ◽  
Taurine Supplementation ◽  
Chronic Social Defeat Stress ◽  
Immobility Time

Abstract Abnormal amino acid metabolism in neural cells is involved in the occurrence and development of major depressive disorder. Taurine is an important amino acid required for brain development. Here, microdialysis combined with metabonomics analysis showed that the level of taurine in the extracellular fluid of the cerebral medial prefrontal cortex (mPFC) was significantly reduced in mice with chronic social defeat stress (CSDS)-induced depression. Therefore, taurine supplementation may be an intervention for depression. We found that taurine supplementation could effectively rescue the decreased preference for sucrose consumption and the increased immobility time during a tail suspension assay and improve social avoidance behaviors in CSDS mice. Moreover, taurine treatment protected the CSDS mice from impairments of dendrite complexity, spine density, and spine ratios. The expression of N-methyl D-aspartate receptor subunit 2A (NR2A), an important synaptic receptor, was largely restored in the mPFC after taurine supplementation. These results demonstrated that taurine exhibited an antidepressive effect by protecting cortical neurons from dendritic spine loss and synaptic protein deficits.

Effects of ethanol on social avoidance induced by chronic social defeat stress in mice

Stress ◽  
2017 ◽  
Vol 20 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Cristiane A. Favoretto ◽  
Giovana C. Macedo ◽  
Isabel M. H. Quadros
Keyword(s):  
Social Defeat ◽  
Social Avoidance ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress

scholarly journals Region-specific myelin differences define behavioral consequences of chronic social defeat stress in mice

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Valentina Bonnefil ◽  
Karen Dietz ◽  
Mario Amatruda ◽  
Maureen Wentling ◽  
Antonio V Aubry ◽  
...  
Keyword(s):  
Social Preference ◽  
Social Defeat ◽  
Editorial Note ◽  
Social Avoidance ◽  
Behavioral Differences ◽  
Social Defeat Stress ◽  
Internodal Length ◽  
Critical Determinant ◽  
Chronic Social Defeat Stress ◽  
Myelin Thickness

Exposure to stress increases the risk of developing mood disorders. While a subset of individuals displays vulnerability to stress, others remain resilient, but the molecular basis for these behavioral differences is not well understood. Using a model of chronic social defeat stress, we identified region-specific differences in myelination between mice that displayed social avoidance behavior (‘susceptible’) and those who escaped the deleterious effect to stress (‘resilient’). Myelin protein content in the nucleus accumbens was reduced in all mice exposed to stress, whereas decreased myelin thickness and internodal length were detected only in the medial prefrontal cortex (mPFC) of susceptible mice, with fewer mature oligodendrocytes and decreased heterochromatic histone marks. Focal demyelination in the mPFC was sufficient to decrease social preference, which was restored following new myelin formation. Together these data highlight the functional role of mPFC myelination as critical determinant of the avoidance response to traumatic social experiences.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

scholarly journals Depressive-Like Behaviors Induced by Chronic Social Defeat Stress Are Associated With HDAC7 Reduction in the Nucleus Accumbens

2021 ◽  
Vol 11 ◽  
Author(s):  
Weijun Qian ◽  
Chao Yu ◽  
Shuai Wang ◽  
Aijun Niu ◽  
Guangyan Shi ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Histone Acetylation ◽  
Histone Deacetylase ◽  
Histone Deacetylases ◽  
Social Defeat ◽  
Social Avoidance ◽  
Social Defeat Stress ◽  
Persistent Symptoms ◽  
Promising Therapeutic Target ◽  
Chronic Social Defeat Stress

Persistent symptoms of depression indicate the adaptive involvement of stable molecules in the brain that may be manifested at the level of chromatin remodeling, such as histone acetylation. Former studies have identified alterations in histone acetylation and deacetylation in several animal models about depression. However, the specific histone deacetylases related with depression are needed to be explored. Here, social avoidance behaviors, anxiety-, and depression-like behaviors were all found in mice suffered from chronic social defeat stress. Moreover, we also discovered that the amount of the class II histone deacetylase, HDAC7 rather than HDAC2, was significantly decreased in the nucleus accumbens of defeated mice, which suggested that HDAC7 might be a crucial histone deacetylase in a chronic social defeat stress model. Our data showed that the depressive-like behaviors induced by chronic social defeat stress were associated with HDAC7 reduction in nucleus accumbens. HDAC7 might be a promising therapeutic target for depression.

scholarly journals Non-coding enhancer RNA regulates NPAS4 in the mPFC to control chronic stress-induced anhedonia-like behavior

2021 ◽  
Author(s):  
Brandon W Hughes ◽  
Benjamin M Siemsen ◽  
Stefano Berto ◽  
Jaswinder Kumar ◽  
Rebecca G Cornbrooks ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Dendritic Spine ◽  
Social Defeat ◽  
Sucrose Preference ◽  
Social Avoidance ◽  
Spine Density ◽  
Rna Seq ◽  
Social Defeat Stress ◽  
Dendritic Spine Density ◽  
Reward Motivation

Abstract Background: Chronic stress can produce reward system deficits (i.e. anhedonia) and other common symptoms associated with depressive disorders, as well as neural circuit hypofunction in the medial prefrontal cortex (mPFC). However, the molecular mechanisms by which chronic stress promotes depressive-like behavior and hypofrontality remain poorly understood. Methods: C57BL/6 adult male mice were subjected to chronic social defeat stress (CSDS). Neuronal PAS domain-containing protein 4 (NPAS4) or the Npas4 lnc-eRNA were reduced using a viral-mediated shRNA approach. CSDS-induced behaviors, including social avoidance, sucrose preference, natural reward motivation, and anxiety-like behavior, were then measured. CSDS-induced changes in mPFC dendritic spine density were assessed using confocal imaging, and the mPFC NPAS4-regulated transcriptome was assessed using RNA-seq analysis. Results: Social defeat stress induced transient expression of NPAS4 in the mPFC. Viral-mediated knockdown of mPFC NPAS4 blocked CSDS-induced reduction in sucrose preference and changes in natural reward motivation, but without influencing social avoidance. NPAS4 was also required for CSDS-induced reduction of pyramidal neuron dendritic spine density in mPFC. RNA-seq analysis from mPFC tissues revealed that NPAS4 influences expression of numerous genes linked to glutamatergic synapses and ribosomal function, and to genes dysregulated in multiple neuropsychiatric disorders, including depression. Finally, we found that stress-induced expression of NPAS4 in mPFC requires a novel, activity-regulated lnc-eRNA, and that this Npas4 lnc-eRNA in mPFC was required for CSDS-induced anhedonia-like behavior. Conclusion: Together our findings reveal a novel, stress-regulated and lnc-eRNA-dependent transcriptional mechanism in the mPFC that promotes dendritic spine loss and development of anhedonia-like behaviors.

scholarly journals Ginsenoside Rb1 Produces Antidepressant-Like Effects in a Chronic Social Defeat Stress Model of Depression Through the BDNF–Trkb Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Jiang ◽  
Hong Huang ◽  
Yiwen Zhang ◽  
Jingwei Lv ◽  
Qiong Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Social Defeat ◽  
Hippocampal Neurogenesis ◽  
Ginsenoside Rb1 ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress ◽  
The Social ◽  
Immobility Time ◽  
Bdnf Signaling ◽  
The Impact

Ginsenoside Rb1 (Rb1), an important bioactive ingredient of Panax ginseng, has potent neuroprotective effects. The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stress (CSDS)–induced depressive-like behaviors and its related mechanism. According to the obtained results, the daily oral administration of Rb1 (35 and 70 mg/kg) and imipramine (15 mg/kg) for 28 days significantly reversed the social avoidance behavior, anhedonia, and behavioral despair via CSDS exposure, as demonstrated by the considerable elevation in the time in the zone in the social interaction test, consumption of sucrose solution in the sucrose preference test, and decrease in immobility time in the forced swim test. Moreover, Rb1 obviously restored the CSDS-induced decrease in the BDNF signaling pathway and hippocampal neurogenesis. Rb1 significantly increased the hippocampal levels of ERK, AKT, and CREB phosphorylation and increased the number of DCX+ cells in DG. Importantly, the antidepressant effects of Rb1 were completely blocked in mice by using K252a (the nonselective tyrosine kinase B inhibitor). In conclusion, our results indicated that Rb1 exerts promising antidepressant-like effects in mice with CSDS-induced depression, and its effects were facilitated by enhancing the BDNF signaling cascade and upregulation of hippocampal neurogenesis.

scholarly journals Hop Bitter Acids Increase Hippocampal Dopaminergic Activity in a Mouse Model of Social Defeat Stress

2020 ◽  
Vol 21 (24) ◽  
pp. 9612
Author(s):  
Yasuhisa Ano ◽  
Shiho Kitaoka ◽  
Rena Ohya ◽  
Keiji Kondo ◽  
Tomoyuki Furuyashiki
Keyword(s):  
Mouse Model ◽  
Chronic Administration ◽  
Social Defeat ◽  
Underlying Mechanism ◽  
Mental Illnesses ◽  
Social Avoidance ◽  
Social Defeat Stress ◽  
Dopaminergic Activity ◽  
Healthy Older Adults ◽  
Bitter Acids

As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown. Since acute oral consumption with IAA increases dopamine levels in hippocampus and improves memory impairment via vagal nerve activation, here we investigated the effects of chronic administration of hop bitter acids on the dopaminergic activity associated with emotional disturbance in a mouse model of repeated social defeat stress (R-SDS). Chronic administration of IAA and MHBA significantly increased dopaminergic activity based on the dopamine metabolite to dopamine ratio in the hippocampus and medial prefrontal cortex following R-SDS. Hippocampal dopaminergic activity was inversely correlated with the level of R-SDS-induced social avoidance with or without IAA administration. Therefore, chronic treatment with hop bitter acids enhances stress resilience-related hippocampal dopaminergic activity.

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.

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