Sex differences in glucocorticoids-induced anabolic effects in rats

Stopa, Larissa Rugila S.; Souza, Camila F. de; Santos, Geisielle Fernandes; Martins, Andressa Busetti; Ferreira, Renan Nascimento; Andrade, Fábio Goulart de; Leite, Cristiane Mota; Zaia, Dimas Augusto Morozin; Zaia, Cássia Thaïs Bussamra Vieira; Uchôa, Ernane Torres

doi:10.1016/j.physbeh.2019.112587

Cited by 10 publications

(7 citation statements)

References 34 publications

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“…The previously published reports indicate increase in bodyweight in CORT treated in comparison to vehicle-treated animals for CORT1 [19] and no significant changes for CORT2 [16]. Here we replicate these finding in CORT1 (increase) and CORT2 (no change) mice and interestingly observe different effects in the female groups with both CORT treatment groups showed overall lower weight increase compared to their corresponding vehicle controls, suggesting distinct metabolic responses of female and male mice to chronic CORT exposure, which is in line with a recent report in female rats [26].…”

Section: Discussionsupporting

confidence: 92%

“…Both CORT treatment protocols have been initially published based upon experiments conducted in male mice, albeit other CORT treatment paradigms have also been applied to female rodents [26,27,28]. These studies have resulted in diverging conclusions regarding the sensitivity of female mice to develop alterations in emotional behavior upon chronic CORT application [27,28].…”

Section: Discussionmentioning

confidence: 99%

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Effect of Chronic Corticosterone Treatment on Depression-Like Behavior and Sociability in Female and Male C57BL/6N Mice

Berger

Gureczny

Reisinger

et al. 2019

Cells

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Depression is a very common psychiatric disorder affecting approximately 300 million people worldwide with the prevalence being twice as high in women as in men. Despite intense research efforts in recent decades, the neurobiological basis underlying depression remains incompletely understood. However, the exposure to chronic stress is widely accepted to constitute a precipitating factor for the development of this mental disorder. Several animal models for the investigation of the pathogenetic link between chronic stress and depression exist and have yielded important insights. The present study aimed at comparing two published protocols for the induction of depression-like behavior in mice based on chronic oral glucocorticoid application. Given the gender distribution in the prevalence of depression, the second goal of this study was to reveal possible differences in the behavioral responses of female and male mice to corticosterone (CORT) treatment. CORT treatment was found to modulate depression-like behavior in selected behavioral paradigms in a sex- and protocol-specific manner. These data are of relevance for the experimental design and interpretation of future studies in the field and further highlight the relevance of “sex as biological variable” to be considered an important parameter for experimental planning and interpretation of results.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Effect of Chronic Corticosterone Treatment on Depression-Like Behavior and Sociability in Female and Male C57BL/6N Mice

Berger

Gureczny

Reisinger

et al. 2019

Cells

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“…have demonstrated increased appetite, weight gain, and adiposity in female mice similar to that seen in male mice (Berger et al 2019, Kaikaew et al 2019 although others have demonstrated a reduction in the metabolic effects of glucocorticoids in female rats albeit at lower doses than those typically used (Stopa et al 2019). In addition, CORT-induced insulin resistance is reportedly less severe in females than in males and, although chronic CORT exposure produced similar increases in adiposity in both sexes, adipose tissue from females demonstrated higher adiponectin secretion, suggesting a more protective adipose phenotype than that of males (Kaikaew et al 2019).…”

mentioning

confidence: 89%

“…It is nevertheless possible that, in spite of a loss in GHSR signaling, the dose of CORT used in this study was high enough that it caused effects that could not be mitigated by blocking GHSR signaling. Perhaps the effects of chronic exposure to lower doses of CORT that also increase food intake and adiposity (15, 25 or 50 µg/L of water) may be mitigated by loss of GHSR signaling (Stopa et al 2019).…”

Section: Figurementioning

confidence: 99%

Ghrelin receptor signaling is not required for glucocorticoid-induced obesity in female mice

Silver

Abbott-Tate

Hyland

et al. 2021

Journal of Endocrinology

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Chronic exposure to high circulating glucocorticoid or ghrelin concentrations increases food intake, weight gain and adiposity, suggesting that ghrelin could contribute to the metabolic effects of chronic glucocorticoids. In male mice, however, blocking ghrelin receptor (GHSR) signalling increased the weight gain and adiposity induced by chronic corticosterone (CORT), rather than attenuating them. In the current study, we investigated the role of GHSR signalling in the metabolic effects of chronic exposure to high circulating CORT in female mice. To do this, female WT and GHSR KO mice were treated with either CORT in a 1% ethanol (EtOH) solution or 1% EtOH alone in their drinking water for 32 days (N=5-8/group). Body weight, food, and water intake as well as vaginal cyclicity were assessed daily. As expected, CORT treatment induced significant increases in body weight, food intake, adiposity and also impaired glucose tolerance. In contrast to results observed in male mice, WT and GHSR KO female mice did not differ on any of these parameters. Neither plasma levels of ghrelin, LEAP-2, the endogenous GHSR antagonist produced by the liver, nor their ratio were altered by chronic glucocorticoid exposure. In addition, CORT treatment disrupted vaginal cyclicity, produced a reduction in sucrose consumption and increased locomotor activity regardless of genotype. Chronic CORT also decreased exploration in WT but not GHSR KO mice. Collectively, these data suggest that most metabolic, endocrine, reproductive and behavioral effects of chronic CORT exposure are independent of GHSR signalling in female mice.

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“…Chronic CORT exposure induces depression-like behavior in rodents [57]. Anhedonia, which refers to loss of interest or pleasure, is a frequent symptom of major depression in humans and is associated with dysfunction of the reward system [58].…”

Section: Discussionmentioning

confidence: 99%

2-Phenylethylamine (PEA) Ameliorates Corticosterone-Induced Depression-Like Phenotype via the BDNF/TrkB/CREB Signaling Pathway

Lee

Kim

Lee

et al. 2020

IJMS

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Depression is a serious medical illness that is one of the most prevalent psychiatric disorders. Corticosterone (CORT) increases depression-like behavior, with some effects on anxiety-like behavior. 2-Phenethylamine (PEA) is a monoamine alkaloid that acts as a central nervous system stimulant in humans. Here, we show that PEA exerts antidepressant effects by modulating the Brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element binding protein (CREB) signaling pathway in CORT-induced depression. To investigate the potential effects of PEA on CORT-induced depression, we first treated CORT (50 μM)-induced hippocampal neurons with 100 μM PEA for 24 h. We found that treatment with CORT altered dendritic spine architecture; however, treatment with PEA rescued dendritic spine formation via regulation of BDNF/TrkB/CREB signaling. Next, we used a mouse model of CORT-induced depression. Mice were treated with CORT (20 mg/kg) for 21 days, followed by assessments of a battery of depression-like behaviors. During the final four days of CORT exposure, the mice were treated with PEA (50 mg/kg). We found that CORT injection promoted depression-like behavior and significantly decreased BDNF and TrkB expression in the hippocampus. However, treatment with PEA significantly ameliorated the behavioral and biochemical changes induced by CORT. Our findings reveal that PEA exerts antidepressant effects by modulating the BDNF/TrkB/CREB signaling pathway in a mouse model of CORT-induced depression.

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Sex differences in glucocorticoids-induced anabolic effects in rats

Cited by 10 publications

References 34 publications

Effect of Chronic Corticosterone Treatment on Depression-Like Behavior and Sociability in Female and Male C57BL/6N Mice

Effect of Chronic Corticosterone Treatment on Depression-Like Behavior and Sociability in Female and Male C57BL/6N Mice

Ghrelin receptor signaling is not required for glucocorticoid-induced obesity in female mice

2-Phenylethylamine (PEA) Ameliorates Corticosterone-Induced Depression-Like Phenotype via the BDNF/TrkB/CREB Signaling Pathway

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