Abstract
Early-life stress can induce marked behavioral and physiological impairments in adulthood including cognitive deficits, depression, anxiety, and gastrointestinal dysfunction. Although robust rat models of early-life stress exist there are few established effective paradigms in the mouse. Genetic background and protocol parameters used are two critical variables in such model development. Thus we investigated the impact of two different early-life stress protocols in two commonly used inbred mouse strains. C57BL/6 and innately anxious BALB/c male mice were maternally deprived 3 h daily, either from postnatal day 1 to 14 (protocol 1) or 6 to 10 (protocol 2). Animals were assessed in adulthood for cognitive performance (spontaneous alternation behavior test), anxiety [open-field, light/dark box (L/DB), and elevated plus maze (EPM) tests], and depression-related behaviors (forced swim test) in addition to stress-sensitive physiological changes. Overall, the results showed that early-life stressed mice from both strains displayed good cognitive ability and no elevations in anxiety. However, paradoxical changes occurred in C57BL/6 mice as the longer protocol (protocol 1) decreased anxiety in the L/DB and increased exploration in the EPM. In BALB/c mice there were also limited effects of maternal separation with both separation protocols inducing reductions in stress-induced defecation and protocol 1 reducing the colon length. These data suggest that, independent of stress duration, mice from both strains were on the whole resilient to the maladaptive effects of early-life stress. Thus maternal separation models of brain–gut axis dysfunction should rely on either different stressor protocols or other strains of mice.
Highlights
Early-life stress has been implicated in the development of longlasting behavioral and physiological alterations such as anxiety, depression, and cognitive impairments in adulthood (Carpenter et al, 2007; Drake et al, 2007; Lazinski et al, 2008; Wachs, 2009; Dinan et al, 2010)
Two-way ANOVA showed an overall maternal separation (MS) effect on bodyweight in BALB/c mice (Figure 2B), from weaning until 13 weeks old [F(2,371) = 19.11, p < 0.0001], as well as a time effect [F(10,371) = 461.26, p < 0.0001], no difference raised on post hoc analysis (p > 0.05 all days); there was no MS × time interaction [F(20,371) = 0.74, p = 0.781]
This absence of general effect of MS on mice is in marked contrast with what is observed in our laboratory using a similar rat model of 3-h daily separation as well
Summary
Early-life stress has been implicated in the development of longlasting behavioral and physiological alterations such as anxiety, depression, and cognitive impairments in adulthood (Carpenter et al, 2007; Drake et al, 2007; Lazinski et al, 2008; Wachs, 2009; Dinan et al, 2010). MS has been reported to induce long-lasting behavioral and physiological changes that can persist into adulthood (Pryce et al, 2005; Macri and Wurbel, 2006; O’Mahony et al, 2009; O’Malley et al, 2010; Uhelski and Fuchs, 2010). Most of these MS protocols have produced reproducible results in rats, attempts to replicate these findings in the mouse have been less than successful, notably due to the difficulty to induce consistent and robust behavioral alterations measurable in adulthood (Millstein and Holmes, 2007; O’Mahony et al, 2011). Given the importance of mice in behavioral genetics research there is a clear need to develop robust mouse models of MS (Jacobson and Cryan, 2007)
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