The response of neuregulin 1 mutant mice to acute restraint stress

Abstract

Stress plays a role in the development and severity of psychotic symptoms and there may be a genetic component to stress vulnerability in schizophrenia. Using an established mouse model for schizophrenia, we investigated the behavioural and endocrine response of Nrg1 transmembrane domain mutant mice (Nrg1 HET) and wild type-like (WT) littermates to acute restraint stress. Animals were screened at 3-4 months and 6-7 months of age (before and after onset of hyperlocomotion) for open field behaviour and serum corticosterone levels. In younger mice, stress reduced locomotive and explorative measures and increased anxietylike behaviour regardless of genotype. Older Nrg1 mutants were less susceptible to the effects of stress on anxiety-related behaviours. All mice responded to restraint stress with robust increases in serum corticosterone. Importantly, the stress-induced increase in corticosterone was more pronounced in Nrg1 mutant than WT mice at the younger but not the older age. Our results suggest that transmembrane domain Nrg1 has only a moderate effect on the acute stress response of mice. The behavioural differences detected between WT and Nrg1 HET mice at the older age were evident without parallel modifications to the glucocorticoid system.

Animal models of gene–environment interaction in schizophrenia: A dimensional perspective

“…In particular, mutants did not display anxiety-like behavior in the open field while WT mice did. Contrary to the behavioral test results, corticosterone response to stress was more pronounced in younger mice (Chesworth et al, 2012). In a different study, the authors applied a subchronic restraint stress paradigm during adolescence (PND 36–49, 30 m/day).…”

Overstimulation of newborn mice leads to behavioral differences and deficits in cognitive performance

“…However, we deliberately and set the volume to 70 decibels, which is well below the levels of 100–115 db that are typically used for acoustic stress models and at a level that has been deemed acceptable by federal guidelines in the United States262728293031. Furthermore, our observation of decreased anxiety and increased travel in our overstimulated mice runs contrary to what has been demonstrated in newborn stress models where increased anxiety is typically seen27282930314344. Finally, stress may be in the causal pathway and mediate the effects of overstimulation.…”

Mouse models of gene–environment interactions in schizophrenia

“…In contrast, acute restraint stress during adulthood (3–4 months and 6–7 months of age) led to different effects. Older NRG1 mutants were less susceptible to the effects of stress on anxietyrelated behaviors than younger mutants (Chesworth et al, 2012). These studies highlight that varying the time of exposure to stressful events leads to differential behavioral alterations in the same transgenic mouse model.…”