Chronic Adolescent Restraint Stress Downregulates miRNA-200a Expression in Male and Female C57BL/6J and BALB/cJ Mice

Abstract

Adolescence is a critical developmental period when the brain is plastic, and stress exposure can have lasting physiological consequences. One mechanism through which adolescent stress may have lasting effects is by altering microRNAs (miRNAs), leading to wide-scale gene expression changes. Three prior independent studies used unbiased approaches (RNA sequencing or microarray) to identify miRNAs differentially expressed by chronic variable stress in male rodents. In all three studies, miRNA-200a was differentially expressed in areas of the brain associated with emotion regulation. The current study extends this research to determine if chronic non-variable adolescent stress downregulates miRNA-200a expression by looking at two strains (BALB/cJ and C57BL/6J) of male and female mice. We utilized a 14-day (2 h/day) restraint stress protocol and verified stress effects on adolescent body weight gain and circulating corticosterone concentrations relative to non-restraint controls. Mice were then left undisturbed until they were euthanized in adulthood, at which time brains were collected to measure miRNA-200a in the ventral hippocampus. Three weeks after adolescent stress ended, differences in body weight between groups were no longer significant; however, animals exposed to stress had less miRNA-200a expression in the ventral hippocampus than control animals. These data implicate miRNA-200a expression as a potential mechanism by which adolescent stress can have persistent impacts on multiple outcomes in both male and female mice.

Keywords: adolescent stress; miR-200a; microRNA; microRNA-200a.

Figure 1

Adolescent body weight depicted as a percentage of day 1 weight across 14 days of restraint stress in male and female BALB/cJ (A) and C57BL/6J (B) mice. N = 5–6/group. * = p < 0.05 main effect of condition, # = p < 0.05 main effect of sex, $ = p < 0.05 condition X sex interaction.

Figure 2

Adult body weight depicted as a percentage of day 1 weight in male and female BALB/cJ (A) and C57BL/6J mice (B). N = 5–6/group. * = p < 0.05 main effect of sex.

Figure 3

Circulating corticosterone (ng/mL) concentrations immediately after the conclusion of the day 14 restraint session in adolescent male and female BALB/cJ (A) and C57BL/6J (B) mice. N = 5–6/group. * = p < 0.05 main effect of condition.

Figure 4

Fold change expression of miRNA-200a in adult male and female BALB/cJ (A) and C57BL/6J (B) mice. Data are combined on sex as there were no main effects or interactions with this variable. N = 5–6/group. * = p < 0.05 main effect of condition.