Effects of Early-Life Stress on Social and Anxiety-Like Behaviors in Adult Mice: Sex-Specific Effects

Abstract

Stressful events in an early postnatal period have critical implications for the individual's life and can increase later risk for psychiatric disorders. The aim of this study was to investigate the influence of early-life stress on the social behavior of adult male and female mice. C57Bl/6 mice were exposed to maternal separation (MS, 3 h once a day) or handling (HD, 15 min once a day) on postnatal day 2 through 14. Adult male and female mice were tested for social behavior in the social interaction test and for individual behavior in the plus-maze and open-field tests. Female mice exposed to maternal separation had increased social behavior and increased anxiety. MS male mice had no changes in social behavior but had significantly disrupted individual behavior, including locomotor and exploratory activity. Handling had positive effects on social behavior in males and females and decreased anxiety in males. Our results support the hypothesis that brief separation of pups from their mothers (handling), which can be considered as moderate stress, may result in future positive changes in behavior. Maternal separation has deleterious effects on individual behavior and significant sex-specific effects on social behavior.

Stress early in life leads to cognitive impairments, reduced numbers of CA3 neurons and altered maternal behavior in adult female mice

“…Based on vaginal cytology, F0 females were subdivided into two groups: diestrous (those in diestrus and metaestrus) and estrous (those in estrus and proestrus). As in our previous study, 16 we did not find a significant effect of cycle phases on most behavioral parameters of F0 females in this work (for details, see Supporting Information, Figure S1). Because the vaginal smear does not always reflect the true phase of the cycle and hormonal level, 50 we excluded cycle phases from analysis.…”

“…Many studies show the critical importance of the postnatal period for individual development because stress in this period can have delayed effects on cognition, individual behavior, neuronal plasticity and epigenetics . Nevertheless, the mouse and rat studies on MS and HD effects on cognition in adult females are limited.…”

“…An adverse early‐life experience results in various structural impairments in the hippocampus . Most research into the effects of early‐life stress on neural plasticity has been performed on male rats . Those studies have showed that prolonged separation from mothers early in life decreases cell proliferation in the Rostral Migratory Stream (on PND 14, PND 21 and PND 28), cell survival, cell differentiation and cell density in the DG on PND 15 .…”

“…The protocol of dam-offspring separation was described previously. 16,42 Briefly, we applied two types of early-life stress from postnatal day 2 (PND 2) to PND 14 (the day of birth was PND 0): prolonged separation of pups from their mothers (maternal separation for 3 hours once a day, MS) and brief separation (handling for 15 minutes once a day, HD). Nonhandled control mice were not separated from dams (normal conditions, NC).…”

“…sensitive to stress; our previous study 16 showed that both positive and negative effects of maternal separation and neonatal handling were more pronounced in female than male mice. A meta-analysis of published papers about the effects of early-life stress 7 indicates that exposure to stress early in life virtually always has effects on behavioral and physiological variables of adult females, whereas the behavior of males is sometimes not subject to changes, or these changes are less pronounced.…”