Distinctive stress sensitivity and anxiety-like behavior in female mice: Strain differences matter

Abstract

Epidemiologic studies have shown that the prevalence of stress-related mood disorders is higher in women, which suggests a different response of neuroendocrine circuits involved in the response to stressful events, as well as a genetic background influence. The aim of this study was to investigate the baseline differences in anxiety-like behaviors of females of two commonly used mice strains. Secondly, we have also aimed to study their behavioral and biochemical alterations following stress. Naïve 3-4 months-old Swiss and C57BL/6 female mice were evaluated in the elevated plus maze (EPM) and in the acoustic startle response (ASR) for anxiety-like behaviors. Besides, an independent group of animals from each strain was exposed to cold-restraint stress (30 min/4 °C, daily) for 21 consecutive days and then evaluated in EPM and in the sucrose consumption tests. Twenty-four hours following behavioral experimentation mice were decapitated and their hippocampi (HP) and cortex (CT) dissected for further Western blotting analysis of glucocorticoid receptor (GR) and glial fibrillary acid protein (GFAP). Subsequent to each behavioral protocol, animal blood samples were collected for further plasma corticosterone analysis. C57BL/6 presented a lower anxiety profile than Swiss female mice in both behavioral tests, EPM and ASR. These phenomena could be correlated with the fact that both strains have distinct corticosterone levels and GR expression in the HP at the baseline level. Moreover, C57BL/6 female mice were more vulnerable to the stress protocol, which was able to induce an anhedonic state characterized by lower preference for a sucrose solution. Behavioral anhedonic-like alterations in these animals coincide with reduced plasma corticosterone accompanied with increased GR and GFAP levels, both in the HP. Our data suggest that in C57BL/6 female mice a dysregulation of the hypothalamus-pituitary-adrenal axis (HPA-axis) occurs, in which corticosterone acting on GRs would possibly exert its pro-inflammatory role, ultimately leading to astrocyte activation in response to stress.

The impact of handling technique and handling frequency on laboratory mouse welfare is sex-specific

“…This observation is in line with the reduced FCM concentrations of the daily handled female mice in our study, underlining the benefit of habituation on the stress response. In general, females, irrespective of the handling method, showed higher concentrations of plasma corticosterone 53 , proposing that females may be more sensitive to handling as for other types of stressors 54,55 . The analysed faecal samples were collected 12 days after the onset of the respective handling, which might have been a sufficient time frame to adapt to the handling stress for all males and the daily handled females, but not for the weekly handled females.…”

Small intestinal flora graft alters fecal flora, stool, cytokines and mood status in healthy mice

“…Both singly housing and repeated intragastric administration procedure caused slight stress. Female C57Bl/6 mice are more susceptive to stress-induced neurobehavioral alterations, such as dysregulation of the HPA axis, whereas male C57Bl/6 mice were reported to be of more resilience ( Hodes et al, 2015 ; Marchette et al, 2018 ; Palumbo et al, 2020 ). Given that the current study aimed at comparing the effects of SIMT and LIMT in healthy host or under physiological condition, only male C57Bl/6 mice thus were used in our study.…”

Effects of restraint stress on the regulation of hippocampal glutamate receptor and inflammation genes in female C57BL/6 and BALB/c mice

“…It is also important to identify potential differences between males and females, especially due to the fact that females are at a greater risk for depressive disorders (Burt and Stein, 2002). Recently, there has been a surge in research studying these differences through a variety of stress paradigms (Bondar et al, 2018; Kuperman et al, 2016; Marrocco et al, 2017; Marchette et al, 2018). We believe that these comparisons can provide useful insight and identify potential avenues for further research regarding sex-dependent differences in stress response and psychiatric diseases.…”