Sex differences in stress responses: a critical role for corticotropin-releasing factor

Bangasser, Debra A.; Wiersielis, Kimberly R.

doi:10.1007/s42000-018-0002-z

Cited by 121 publications

(85 citation statements)

References 121 publications

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“…In rodents, sex differences have been found in every aspect of CRF function from the inputs that regulate CRF neurons to CRF's postsynaptic efficacy (for review, see Bangasser & Wiersielis, ). In the PVN, there are several reports that female rats had greater CRF expression than males (Duncko, Kiss, Skultetyova, Rusnak, & Jezova, ; Viau et al, ), although this difference was not found in every rat study or with the Crh‐IRES‐Cre::Ai14 (tdTomato) reporter mouse (Sterrenburg et al, ; Walker, Cornish, Lawrence, & Campbell, ).…”

Section: Sex Differences In the Crf Systemmentioning

confidence: 99%

Sex differences in the hypothalamic–pituitary–adrenal axis: An obstacle to antidepressant drug development?

Kokras

Hodes

Bangasser

et al. 2019

British J Pharmacology

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Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has long been implicated in the pathophysiology of depression, and HPA axis-based compounds have served as potential new therapeutic targets, but with no success. This review details sex differences from animal and human studies in the function of HPA axis elements (glucocorticoids, corticotropin releasing factor, and vasopressin) and related compounds tested as candidate antidepressants. We propose that sex differences contribute to the failure of novel HPA axis-based drugs in clinical trials. Compounds studied preclinically in males were tested in clinical trials that recruited more, if not exclusively, women, and did not control, but rather adjusted, for potential sex differences. Indeed, clinical trials of antidepressants are usually not stratified by sex or other important factors, although preclinical and epidemiological data support such stratification. In conclusion, we suggest that clinical testing of HPA axis-related compounds creates an opportunity for targeted, personalized antidepressant treatments based on sex.

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Section: Sex Differences In the Crf Systemmentioning

confidence: 99%

Sex differences in the hypothalamic–pituitary–adrenal axis: An obstacle to antidepressant drug development?

Kokras

Hodes

Bangasser

et al. 2019

British J Pharmacology

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“…This could be due to female mice having naturally higher baseline corticosterone than males (e.g., Malisch et al, 2007), which we cannot test given that not all of our serum samples were taken quickly enough (limit is 2-3 min). Another possibility is that females are more sensitive to human presence or to the stress of being captured, which would fit with findings in other species of a sex difference in glucocorticoid production in response to stressors (reviewed in Bangasser and Wiersielis, 2018).…”

Section: Discussionmentioning

confidence: 74%

Immune-Endocrine Links to Gregariousness in Wild House Mice

Lopes

Carlitz

Kindel

et al. 2020

Front. Behav. Neurosci.

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Social interactions are critically important for survival and impact overall-health, but also impose costs on animals, such as exposure to contagious agents. The immune system can play a critical role in modulating social behavior when animals are sick, as has been demonstrated within the context of "sickness behaviors." Can immune molecules affect or be affected by social interactions even when animals are not sick, therefore serving a role in mediating pathogen exposure? We tested whether markers of immune function in both the blood and the brain are associated with gregariousness, quantified as number of animals interacted with per day. To do this, we used remote tracking of social interactions of a wild population of house mice (Mus musculus domesticus) to categorize animals in terms of gregariousness. Blood, hair, brain and other tissue samples from animals with extreme gregariousness phenotypes were collected. We then tested whether the levels of three important cytokines (TNF-α, IFN-γ and IL-1β) in the serum, cortex and hypothalamus of these animals could be explained by the gregariousness phenotype and/or sex of the mice. Using the hair as a long-term quantification of steroid hormones, we also tested whether corticosterone, progesterone and testosterone differed by social phenotype. We found main effects of gregariousness and sex on the serum levels of TNF-α, but not on IFN-γ or IL-1β. Brain gene expression levels were not different between phenotypes. All hair steroids tended to be elevated in animals of high gregariousness phenotype, independent of sex. In sum, elements of the immune system may be associated with gregariousness, even outside of major disease events. These results extend our knowledge of the role that immune signals have in contributing to the regulation of social behaviors outside periods of illness.

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“…Numerous sex differences have been reported in the functioning of the stress neuropeptide, corticotropin-releasing factor (CRF), with differences in receptor expression, distribution, trafficking and signaling (reviewed in (Bangasser & Wiersielis, 2018)). The majority of these differences lead to enhanced CRF efficacy in females, which may lead to heightened sensitivity to stressors in females.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in fear regulation and reward seeking behaviors in a fear-safety-reward discrimination task

Greiner

Norris

Müller

et al. 2018

Preprint

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Reward availability and the potential for danger or safety potently regulates emotion. Despite women being more likely than men to develop emotion dysregulation disorders, there are comparatively few studies investigating fear, safety and reward regulation in females. Here, we show that female Long Evans rats do not suppress conditioned freezing in the presence of a safety cue, nor do they extinguish their freezing response, whereas males do both. Females were also more reward responsive during the reward cue until the first footshock exposure, at which point there were no sex differences in reward seeking to the reward cue. Darting analyses indicate females might be able to regulate this behavior in response to the safety cue, suggesting they might be able to discriminate between fear and safety cues but do not demonstrate this with conditioned suppression of the freezing behavior. However, levels of darting in this study were too low to make any clear conclusions. In summary, females showed a significantly different behavioral profile than males in a task that tests the ability to discriminate among fear, safety and reward cues. This paradigm offers a great opportunity to test for mechanisms that are generating these behavioral sex differences in learned safety and reward seeking.

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Sex differences in stress responses: a critical role for corticotropin-releasing factor

Cited by 121 publications

References 121 publications

Sex differences in the hypothalamic–pituitary–adrenal axis: An obstacle to antidepressant drug development?

Sex differences in the hypothalamic–pituitary–adrenal axis: An obstacle to antidepressant drug development?

Immune-Endocrine Links to Gregariousness in Wild House Mice

Sex differences in fear regulation and reward seeking behaviors in a fear-safety-reward discrimination task

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