New knockout model confirms a role for androgen receptors in regulating anxiety-like behaviors and HPA response in mice

Chen, Chieh V.; Brummet, Jennifer L.; Lonstein, Joseph S.; Jordan, Cynthia L.; Breedlove, S. Marc

doi:10.1016/j.yhbeh.2014.01.001

Cited by 48 publications

(36 citation statements)

References 68 publications

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“…Few studies have investigated the impact of the timing of the administration of specific hormones on anxiety‐like behaviour. The anxiolytic action of testosterone in the male mouse may be limited to the light phase . Similarly, in mice lacking the NPY receptor Y1, alterations in anxiety‐like behaviour were only observed during the light phase .…”

Section: Discussionmentioning

confidence: 99%

Neuroendocrine Regulation of Anxiety: Beyond the Hypothalamic‐Pituitary‐Adrenal Axis

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Stranahan

Suchecki

et al. 2016

J Neuroendocrinology

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The central nervous system regulates and responds to endocrine signals, and this reciprocal relationship determines emotional processing and behavioural anxiety. Although the hypothalamicpituitary-adrenal (HPA) axis remains the best-characterised system for this relationship, other steroid and peptide hormones are increasingly recognised for their effects on anxiety-like behaviour and reward. The present review examines recent developments related to the role of a number of different hormones in anxiety, including pregnane neurosteroids, gut peptides, neuropeptides and hormonal signals derived from fatty acids. Findings from both basic and clinical studies suggest that these alternative systems may complement or occlude stress-induced changes in anxiety and anxiety-like behaviour. By broadening the scope of mechanisms for depression and anxiety, it may be possible to develop novel strategies to attenuate stress-related psychiatric conditions. The targets for these potential therapies, as discussed in this review, encompass multiple circuits and systems, including those outside of the HPA axis.

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Section: Discussionmentioning

confidence: 99%

Neuroendocrine Regulation of Anxiety: Beyond the Hypothalamic‐Pituitary‐Adrenal Axis

Borrow

Stranahan

Suchecki

et al. 2016

J Neuroendocrinology

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“…Sections were processed for androgen receptor immunohistochemistry according to a previously published protocol (Chen et al, 2014). Sections were rinsed in three 10 min washes in a phosphate-buffered gelatin Triton solution (PBS-GT; 0.1% gelatin, 0.3% Triton X-100, in PBS, pH 7.4), followed by 0.5% sodium borohydride in PBS-GT for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Winning agonistic encounters increases testosterone and androgen receptor expression in Syrian hamsters

Clinard

Barnes

Adler

et al. 2016

Hormones and Behavior

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Winning aggressive disputes is one of several experiences that can alter responses to future stressful events. We have previously tested dominant and subordinate male Syrian hamsters in a conditioned defeat model and found that dominant individuals show less change in behavior following social defeat stress compared to subordinates and controls, indicating a reduced conditioned defeat response. Resistance to the effects of social defeat in dominants is experience-dependent and requires the maintenance of dominance relationships for 14 days. For this study we investigated whether winning aggressive interactions increases plasma testosterone and whether repeatedly winning increases androgen receptor expression. First, male hamsters were paired in daily 10-min aggressive encounters and blood samples were collected immediately before and 15-min and 30-min after the formation of dominance relationships. Dominants showed an increase in plasma testosterone at 15-min post-interaction compared to their pre-interaction baseline, whereas subordinates and controls showed no change in plasma testosterone. Secondly, we investigated whether 14 days of dominant social status increased androgen or estrogen alpha-receptor immunoreactivity in brain regions that regulate the conditioned defeat response. Dominants showed more androgen, but not estrogen alpha, receptor immuno-positive cells in the dorsal medial amygdala (dMeA) and ventral lateral septum (vLS) compared to subordinates and controls. Finally, we showed that one day of dominant social status was insufficient to increase androgen receptor immunoreactivity compared to subordinates. These results suggest that elevated testosterone signaling at androgen receptors in the dMeA and vLS might contribute to the reduced conditioned defeat response exhibited by dominant hamsters.

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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.

show abstract

New knockout model confirms a role for androgen receptors in regulating anxiety-like behaviors and HPA response in mice

Cited by 48 publications

References 68 publications

Neuroendocrine Regulation of Anxiety: Beyond the Hypothalamic‐Pituitary‐Adrenal Axis

Neuroendocrine Regulation of Anxiety: Beyond the Hypothalamic‐Pituitary‐Adrenal Axis

Winning agonistic encounters increases testosterone and androgen receptor expression in Syrian hamsters

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

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