Prolonged Maternal Separation Induces the Depression-Like Behavior Susceptibility to Chronic Unpredictable Mild Stress Exposure in Mice

Abstract

Early life stress is an important determinant for developing depression later in life. It is reported that maternal separation (MS) could trigger stress sensitivity in adulthood when exposed to stress again. However, it could also result in resilience to stress-induced depression. The conclusions are contradictory. To address this issue, C57BL/6N newborn pups were exposed to either daily short MS (MS for 15 min per day; MS15) or prolonged MS (MS for 180 min per day; MS180) from the first day postpartum (PD1) to PD21. Adult mice were then subjected to chronic unpredictable mild stress (CUMS) exposure from PD64 to PD105. The behavior tests such as the forced swimming test (FST), tail suspension test (TST), and open-field test were performed once a week during this time. Besides, the hippocampal neurosteroids, serum stress hormones, and hippocampal monoamine neurotransmitters were measured at PD106. We found that mice in the MS180 group displayed the reduced struggling time and the increased latency to immobility in both FST and TST. However, there was no significant difference in the MS15 group. The levels of hippocampal neurosteroids (progesterone and allopregnanolone) were decreased, and the serum levels of corticosterone, corticotropin-releasing hormone, and adrenocorticotropic hormone were overexpressed in the MS180 group. Besides, the expressions of monoamine neurotransmitters such as 5-hydroxytryptamine and 5-hydroxy indole acetic acid significantly decreased in the MS180 group, but not in the MS15 group. All findings revealed that prolonged MS, rather than short MS, could increase the susceptibility to depression-like behavior when reexposed to stress in adulthood. However, future studies are warranted to identify the underlying neuromolecular mechanism of the MS experience on the susceptibility to adult stress reexposure.

Early life stress induces visual dysfunction and retinal structural alterations in adult mice

“…Therefore, we assessed the effect of MSEW on visual function from a wider perspective. ELS affects the performance in several behavioral tests at the adult stage, such as the open field, the elevated plus maze, the forced swimming, the sucrose preference, and the tail suspension tests, among others (Bian et al, 2021; Han et al, 2019; Qin et al, 2021); however, the effect of MSEW on behavioral tests specifically based on vision had not been previously reported. The virtual cliff test evaluates binocular depth perception as a result of the functional integrity of the retino–geniculo–cortical pathway (Fox, 1965), and the looming response, a reflex also exclusively relying on visual cues (Yilmaz & Meister, 2013), evaluates the integrity of the retino–colicular pathway.…”

Brief Maternal Separation Inoculates Against the Effects of Social Stress on Depression-Like Behavior and Cocaine Reward in Mice

“…These results contrast with data showing that MS increases social avoidance and induces anxiety- and depression-like behavior ( Bian et al, 2015 ; Rana et al, 2015 ; Shin et al, 2016 ; Alves et al, 2020 ; He et al, 2020 ); nevertheless, it should be taken into account that these studies included repeated experiences of MS, while we used a single MS episode in order to induce a mild stress. In this line, a recent study has demonstrated that prolonged MS (3h/day, from PND1-21), but not short MS (15 min/day, from PND1-21), increases susceptibility to depression-like behavior when mice are exposed to chronic unpredictable mild stress in adulthood ( Bian et al, 2021 ). In the present study, mice exposed to a brief MS became resilient to the depression-like behavior induced by exposure to IRSD in late adolescence (as indicated by changes in the latency of grooming).…”

Age, β-endorphin, and sex dependent effects of maternal separation on locomotor activity, anxiety-like behavior, and alcohol reward

“…In rodents, maternal separation (MS) between 180 and 360 min disrupts maternal care and is associated with a variety of negative outcomes in adulthood (for example, see: Huot et al, 2001 ; Pryce and Feldon, 2003 ; Rüedi-Bettschen et al, 2006 ; Cruz et al, 2008 ; Amini-Khoei et al, 2019 ; Bian et al, 2021 ). However, variation in separation parameters, timing and type of dependent measures, and strains and species employed, contribute to substantial variability in the basic science literature ( Nylander and Roman, 2013 ; Tractenberg et al, 2016 ; Wang et al, 2020 ).…”

“…In rodents, maternal separation (MS) between 180 and 360 min disrupts maternal care and is associated with a variety of negative outcomes in adulthood (for example, see: Huot et al, 2001;Pryce and Feldon, 2003;Rüedi-Bettschen et al, 2006;Cruz et al, 2008;Amini-Khoei et al, 2019;Bian et al, 2021). However, variation in These were dependent up sex and pup treatment, larger in female and maternally separated subjects.…”