Sex-specific effects of social defeat stress on miRNA expression in the anterior BNST

Luo, Pei; Manning, Claire; Fass, Joe N.; Williams, Alexia; Hao, Rebecca; Campi, Katharine L.; Trainor, Brian C.

doi:10.1016/j.bbr.2020.113084

Cited by 16 publications

(10 citation statements)

References 94 publications

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“…Several in vivo studies indicate that miRNAs could be involved in vulnerability and resilience to stress-related mental disorders [21][22][23], as well as in stress-related sex differences [24,25]. However, the contribution of miRNA to the mechanism of sex-related individual patterns of trauma response, was not yet systematically studied.…”

Section: Introductionmentioning

confidence: 99%

Sex-specific roles of hippocampal microRNAs in stress vulnerability and resilience

et al. 2022

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Contrary to intuition, most individuals are resilient to psychological trauma and only a minority is vulnerable. Men and women are known to respond differently to trauma exposure, however, mechanisms underlying the relationship between sex differences and trauma resilience and vulnerability are not yet fully understood. Taking advantage of the Behavioral Profiling approach, which enables differentiating between ‘affected’ and ‘unaffected’ individuals, we examined sex-associated differences in stress exposure effects on hippocampal expression of selected stress-related GABA-A receptor targeting miRNAs. Levels of the miRNA-144 and miRNA-33 were measured in male and female affected (vulnerable, e.g., higher freezing time) and unaffected (resilient) rats. In male rats, increased levels of miRNA-144 and miRNA-33 were observed in the dorsal dentate gyrus (dDG) and ventral dentate gyrus (vDG) respectively, of stress-exposed but unaffected animals. In females, we observed an increased expression of miRNA-144 and miRNA-33 in the ventral cornu ammonis 1 (vCA1) of affected animals. Accordingly, we inhibited miRNAs expression selectively in hippocampal subregions using oligonucleotides containing locked nucleic acid bases, to examine the miRNAs’ causal contribution to either vulnerability or resilience to stress in each sex. Inhibition of miRNA-144 in dDG and miRNA-33 in vDG in males resulted in an increased prevalence of vulnerable animals, while inhibition of miRNA-144 and miRNA-33 in vCA1 in females increased the proportion of resilient animals. The current findings reveal a critical sex-associated difference in the role of miRNAs in stress vulnerability and resilience. This novel understanding of sex-associated epigenetic involvement in the mechanism of stress-related psychopathologies may help improve gender-specific diagnosis and effective treatment.

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Section: Introductionmentioning

confidence: 99%

Sex-specific roles of hippocampal microRNAs in stress vulnerability and resilience

et al. 2022

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“…Rather, here we take advantage of the OSS procedure to compare stressed mice to their same-sex controls, revealing unexpected differences in social decision making and reward seeking between sexes. We designed OSS to be modular, and future iterations will incorporate variations of female social defeat stress 54,[56][57][58][59][60] and male witness defeat stress 27 , to allow direct behavioral and neurophysiological comparisons across sexes.…”

Section: Discussionmentioning

confidence: 99%

Individual differences in volitional social motivation in male and female mice following social stress

Navarrete

Schneider

Smith

et al. 2022

Preprint

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Background: A key challenge in developing new treatments for neuropsychiatric illness is the disconnect between preclinical models and the complexity of human social behavior. We aimed to integrate voluntary social self-administration into a preclinical rodent stress model, as a platform for the identification of basic brain and behavior mechanisms underlying stress-induced individual differences in social motivation. Here, we introduce an operant social stress (OSS) procedure with male and female mice, where lever presses are reinforced by freely moving social interaction with a familiar social partner across social stress exposure. Methods: OSS is composed of three phases: (i) social self-administration training, (ii) social stress concurrent with daily reinforced social self-administration testing, and (iii) post-stress operant social reward testing under both non-reinforced and reinforced conditions. We resolve social stress-induced changes to social motivation behaviors using hierarchical clustering and aggregated z-scores, capturing the spectrum of individual differences that we describe with a social index score. Results: OSS captures a range of stress-related dynamic social motivation behaviors inclusive of sex as a biological variable. Both male and female mice lever press for access to a social partner, independent of social partner coat color or familiarity. Social stress attenuates social self-administration in males and promotes social reward seeking behavior in females. Hierarchical clustering does not adequately describe the relative distributions of social motivation following stress, which we find is better described as a non-binary behavioral distribution that we define by introducing the social index score. This index is stable across individual mice. Conclusion: We demonstrate that OSS can be used to detect stable individual differences in stress-induced changes to social motivation in male and female mice. These differences may reflect unique neurobiological, cellular and circuit mechanisms not captured by preclinical models that omit voluntary social behaviors. The inclusion of volitional social procedures may enhance the understanding of behavioral adaptations promoting stress resiliency and their mechanisms under more naturalistic conditions.

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“…Due to our current lack of consensus on the pathology and etiology of depression, there is a large gap between experimental animals and humans, which cannot fully simulate some of the core symptoms of depression, such as low mood, feelings of worthlessness, and recurrent thoughts of death or suicide [84]. The extent to which animal models of depression reflect human pathophysiological processes is also uncertain, and therefore the results of animal models are not…”

Section: Patient Tissuementioning

confidence: 99%

Research progress of miRNA in different depression model samples

Zhang¹

2022

AETR

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Depression is a mood disorder characterized by prolonged depressed mood, lack of interest and pleasure, and low self-assessment. The miRNAs, as single-stranded non-coding RNA molecules that can participate in post-transcriptional regulation of gene expression, regulate physiological processes by degrading mRNAs or inhibiting the translation of their target genes to achieve gene silencing. Numerous studies have revealed an in-depth understanding of depression-related miRNA changes and the role they play in the pathogenesis of depression, and miRNAs have received widespread attention as therapeutic targets. This review summarizes the expression of miRNAs in different depression samples (patients, rats, and mice) and the corresponding regulatory pathways. The analysis revealed the existence of miRNAs with consistent expression trends in different samples, and the discovery of these miRNAs provides new insights into their use as therapeutic targets in depression.

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Sex-specific effects of social defeat stress on miRNA expression in the anterior BNST

Cited by 16 publications

References 94 publications

Sex-specific roles of hippocampal microRNAs in stress vulnerability and resilience

Sex-specific roles of hippocampal microRNAs in stress vulnerability and resilience

Individual differences in volitional social motivation in male and female mice following social stress

Research progress of miRNA in different depression model samples

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