The role of developmental and environmental factors in a mouse model of high emotional reactivity

Murra D, Hilde KL, Wei Q, Zhang L, Hebda-Bauer EK, Freeman Z, Watson SJ, Akil H
Society for Neuroscience. 2019.


Early life adversity and genetic factors both influence the development and expression of mood disorders and future emotional reactivities to stress. Although numerous studies have sought to describe individual factors that predispose adults to depression, anxiety, and other psychiatric disorders, the interplay and hierarchy of these individual factors and their combinations are not fully understood. In this study, we sought to incorporate a genetic mouse model of predisposition to emotional lability, multiple environmental stress models, and various behavioral outcomes to untangle the many factors that influence the propensity of developing adult anxiety and depression-like behavior. Genetically, we have previously shown that constitutive overexpression of the glucocorticoid receptor (GRov) in the forebrain during only the first 3 weeks of life resulted in long-lasting gene-expression changes and increased anxiety-like behavior in adulthood. Because of their role in the transduction of the stress responses, glucocorticoid hormones and their receptors serve as both genetic factors and mediators environmental influences, and thus the extent of emotional reactivity. Moreover, we compared two models of early life stress: maternal separation and developmental enrichment to ask what environmental manipulations change the genetic and control susceptibility to subsequent adulthood anxiety-like behavior. We used those individual factors and their combinations, that when expressed during a critical period of development(P1-P21), to induce future vulnerability or resilience to anxiety-like behavior. Moreover, we were able to further manipulate those factors in adulthood with group and single housing to test the stability of each factor to carry on its behavioral phenotype. Finally, this then allowed us to create a hierarchy model of environmental and genetic interactions that influence emotional reactivity.!/7883/presentation/44109