Beyond the HPA-axis: The role of the gonadal steroid hormone receptors in modulating stress-related responses in an animal model of PTSD

Fenchel, Daphna; Levkovitz, Yechiel; Vainer, Ella; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

doi:10.1016/j.euroneuro.2015.02.004

Cited by 31 publications

(19 citation statements)

References 47 publications

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“…Moreover, exposure to stress, and more specifically stress-induced HPA activity, appears to inhibit estrogen and testosterone secretion (Lu et al, 2015; Toufexis et al, 2014). For instance, male rats exposed to predator odor stress showed reduced levels of testosterone (Fenchel et al, 2015). Female rats also exhibited a significant decrease in plasma levels of estrogen and testosterone following foot shock and chronic unpredictable mild stress (Lu et al, 2015).…”

Section: Gonadal Hormones Stress and Fear Extinctionmentioning

confidence: 99%

Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones

Maeng

Milad

2015

Hormones and Behavior

300

199

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Women are more vulnerable to stress- and fear-based disorders, such as anxiety and post-traumatic stress disorder. Despite the growing literature on this topic, the neural basis of these sex differences remains unclear, and the findings appear inconsistent. The neurobiological mechanisms of fear and stress in learning and memory processes have been extensively studied, and the crosstalk between these systems is beginning to explain the disproportionate incidence and differences in symptomatology and remission within these psychopathologies. In this review, we discuss the intersect between stress and fear mechanisms and their modulation by gonadal hormones and discuss the relevance of this information to sex differences in anxiety and fear-based disorders. Understanding these converging influences is imperative to the development of more effective, individualized treatments that take sex and hormones into account.

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Section: Gonadal Hormones Stress and Fear Extinctionmentioning

confidence: 99%

Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones

Maeng

Milad

2015

Hormones and Behavior

300

199

View full text Add to dashboard Cite

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“…Putative binding factors were predicted using SpaMo directly from the DREME suite software package and are listed in the tables shown with their putative transcription factors. The literature (Ref) links of each TF to psychiatric disorders are shown: Scz (schizophrenia); BP (Bipolar Disorder); MDD (Major Depressive Disorder); PTSD (Post-Traumatic Stress Disorder) (Chen et al, 2014a; Fenchel et al, 2015; Geng et al, 2007; Hart et al, 2012; Kumar et al, 2005; Liang et al, 2011; Mamdani et al, 2011; Pamment et al, 2002; Shiota et al, 2011). …”

Section: Figurementioning

confidence: 99%

Sex-specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress

Papale

Madrid

et al. 2016

Neurobiology of Disease

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Environmental stress is among the most important contributors to increased susceptibility to develop psychiatric disorders. While it is well known that acute environmental stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive epigenetic modification that is highly enriched in neurons and is associated with active neuronal transcription. Recently, we reported a genome-wide disruption of hippocampal 5hmC in male mice following acute stress that was correlated to altered transcript levels of genes in known stress related pathways. Since sex-specific endocrine mechanisms respond to environmental stimulus by altering the neuronal epigenome, we examined the genome-wide profile of hippocampal 5hmC in female mice following exposure to acute stress and identified 363 differentially hydroxymethylated regions (DhMRs) linked to known (e.g., Nr3c1 and Ntrk2) and potentially novel genes associated with stress response and psychiatric disorders. Integration of hippocampal expression data from the same female mice found stress-related hydroxymethylation correlated to altered transcript levels. Finally, characterization of stress-induced sex-specific 5hmC profiles in the hippocampus revealed 778 sex-specific acute stress-induced DhMRs some of which were correlated to altered transcript levels that produce sex-specific isoforms in response to stress. Together, the alterations in 5hmC presented here provide a possible molecular mechanism for the adaptive sex-specific response to stress that may augment the design of novel therapeutic agents that will have optimal effectiveness in each sex.

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“…The HPA axis secretes glucocorticoids to maintain biological homeostasis and adapt to chronic stress in response to stress (Wilson et al, 2014). Fenchel et al (2015) reported that gonadal steroid hormones (GSHs) are involved in the neurobiological response to predator scent stress, modulating anxiety-like responses in an animal model. Interestingly, the HPA and HPG axes could be intermediary mechanisms underlying the life adversity symptoms observed in patients with PTSD.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic mechanism of maternal post-traumatic stress disorder in delayed rat offspring development: dysregulation of methylation and gene expression

X-G

Zhang

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Maternal post-traumatic stress disorder (PTSD) increases the risk of adverse neurodevelopmental outcomes in the child. Epigenetic alternations may play an essential role in the negative effects of PTSD. This study was aimed to investigate the possible epigenetic alterations of maternal PTSD, which underpins the developmental and behavioral impact. 24 pregnant Sprague-Dawley (SD) rats were randomly grouped into PTSD and control groups. Open-field tests (OFTs), elevated pull maze (EPM) assays, gene expression profile chip tests, and methylated DNA immunoprecipitation sequencing (MeDIPSeq) were performed on the offsprings 30 days after birth. The results 2 X.G. Zhang et al. Genetics and Molecular Research 15 (3): gmr.15039009 showed that PTSD offsprings had lower body weights and OFT scores than control offsprings. Enzyme-linked immunosorbent assays showed that serotonin receptor (5-HT) and dopamine levels were significantly lower in PTSD offsprings than in control offsprings. In contrast, corticosterone levels were higher in the PTSD group than in the control group. In a comparison of the PTSD group versus the control group, 4,160 significantly differentially methylated loci containing 30,657 CpGs were identified; 2,487 genes, including 13 dysmethylated genes, were validated by gene expression profiling, showing a negative correlation between methylation and gene expression (R = -0.617, P = 0.043). In conclusion, maternal PTSD could delay the physical and behavioral development of offsprings, and the underlying mechanism could contribute to changes in neurotransmitters and gene expression, owing to dysregulation of wholegenome methylation. These findings could support further clinical research on appropriate interventions for maternal PTSD to prevent methylation dysregulation and developmental retardation.

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Beyond the HPA-axis: The role of the gonadal steroid hormone receptors in modulating stress-related responses in an animal model of PTSD

Cited by 31 publications

References 47 publications

Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones

Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones

Sex-specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress

Epigenetic mechanism of maternal post-traumatic stress disorder in delayed rat offspring development: dysregulation of methylation and gene expression

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