Strain-specific cognitive deficits in adult mice exposed to early life stress.

Abstract

Early life stress is a prominent risk factor for the development of adult psychopathology. Numerous studies have shown that early life stress leads to persistent changes in behavioral and endocrine responses to stress. However, despite recent findings of gene expression changes and structural abnormalities in neurons of the forebrain neocortex, little is known about specific cognitive deficits that can result from early life stress. Here we examined five cognitive functions in two inbred strains of mice, the stress-resilient strain C57Bl/6 and the stress-susceptible strain Balb/c, that were exposed to an infant maternal separation (IMS) paradigm and raised to adulthood. Between postnatal ages P60 to P90, mice underwent a series of tests examining five cognitive functions: Recognition memory, spatial working memory, associative learning, shifts of attentional sets, and reversal learning. None of these functions were impaired in IMS C57Bl/6 mice. In contrast, IMS Balb/c mice exhibited deficits in spatial working memory and extradimensional shifts of attention, i.e., functions governed primarily by the medial prefrontal cortex. Thus, like recently discovered changes in frontocortical gene expression, the emergence of specific cognitive deficits associated with the medial prefrontal cortex is also strain-specific. These findings illustrate that early life stress can indeed affect specific cognitive functions in adulthood, and they support the hypothesis that the genetic background and environmental factors are critical determinants in the development of adult cognitive deficits in subjects with a history of early life stress. Keywordsearly life stress; inbred mouse strains; recognition memory; working memory; attention setshifting For several heritable psychiatric disorders, the interaction between gene and environment is thought to be critical for modulating outcome or mutating genetic risk (Kendler, 2005;Kendler and Baker, 2007). This is best documented for mood disorders in subjects with distinct genetic variants in serotonin-related genes (Caspi et al., 2010). Moreover, the impact of environmental factors on the development of psychopathology depends upon the age of

An overview of maternal separation effects on behavioural outcomes in mice: Evidence from a four-stage methodological systematic review

“…In the same way, it is difficult to determine if one sex is more susceptible to MS effects, because the anxiety-25 like behaviour findings were inconsistent. Nonetheless, when comparing BALB/c mice to C57BL/6 mice and other strains, BALB/c appeared to have the most stresssusceptible profile because findings in this strain were less contradictory, suggesting adverse effects in response to MS were higher (Mehta and Schmauss, 2011;Millstein and Holmes, 2007). This also reinforces the hypothesis that BALB/c could be the strain of choice when investigating postnatal manipulation effects.…”

“…Previous findings indicate that certain mice strains differ in regard to specific behavioural phenotypes and exhibit different responses to environmental challenges and postnatal stressors (Holmes et al, 2005;Kundakovic et al, 2013;Mehta and Schmauss, 2011). C57BL/6 mice, for instance, when compared to BALB/c mice, are more resistant to stress-induced effects early in life (Holmes et al, 2005;Mehta and Schmauss, 2011).…”

“…C57BL/6 mice, for instance, when compared to BALB/c mice, are more resistant to stress-induced effects early in life (Holmes et al, 2005;Mehta and Schmauss, 2011).…”

Maternal separation induces hippocampal changes in cadherin-1 (CDH-1) mRNA and recognition memory impairment in adolescent mice

“…MATERNAL SEPARATION, RECOGNITION MEMORY AND CADHERIN mRNA 4 Specifically, previous studies have suggested that the BALB/c is one of the most vulnerable mice strain to the MS effects later in life (Mehta & Schmauss, 2011;Millstein & Holmes, 2007;Tractenberg et al, 2016). In this context, daily-prolonged periods of maternal separation (MS) were associated with long-term neurobiological and behavioral consequences (Millstein & Holmes, 2007;Tractenberg et al, 2016;Viola et al, 2016;Wearick-Silva et al, 2016).…”

Differential susceptibility of BALB/c, C57BL/6N, and CF1 mice to photoperiod changes

“…BALB/c mice, but not C57BL/6 mice, have exhibited deficits in spatial working memory and shifts of attention following infant maternal separation. 24 Unpredictable chronic mild stress has induced coat deterioration and decreased grooming behavior in BALB/c mice but not Swiss mice. 25 It is therefore not surprising that BALB/c is usually the strain of choice for studies in which stress plays a central role, such as studies on depression and/or antidepressant effects.…”