Mechanisms of hippocampal development: Molecular and cellular phenotypes in the selectively bred high-responder/low-responder model of affective disorders
Hilde KL, Hagenauer MH, Stefanov AV, Birt I, Hebda-Bauer EK, Watson SJ Jr, Akil H
Society for Neuroscience. 2018.
Mood disorders have complex etiologies that originate from an interplay between genetic and environmental factors. Although numerous gene expression changes have been described in adults with depression, anxiety, and other mood disorders, the underlying developmental mechanisms that predispose individuals for psychiatric disorders in adulthood are less well understood. In this study, we utilize a selectively bred rat model of high responder (HR) and low responder (LR) animals that represent extreme ends of the behavioral spectrum in their baseline propensity for anxiety- and depressive-like behavior, as well as their response to environmental factors such as stress.
We identify molecules that are differentially expressed in HR and LR animals during developmental stages that are critical for establishing proper molecular and cellular composition of the postnatal hippocampus. Using gene expression analyses, cell fate studies, pharmacological manipulation, and behavioral testing we study the mechanisms that contribute to the proper development of the hippocampus, the response of these molecules to stress, and test their role in the emergence of anxiety- and depressive-like behaviors in adulthood.