Psychosocial stress, glucocorticoids, and structural alterations in the tree shrew hippocampus

Abstract

Animal models for chronic stress represent an indispensable preclinical approach to human pathology since clinical data point to a major role of psychological stress experiences, acute and/or chronic, to the development of behavioral and physiological disturbances. Chronic emotional arousal is a consequence of various types of social interactions, and one major neurohumoral accompaniment is the activation of the classic stress circuit, the limbic–hypothalamic–pituitary–adrenocortical (LHPA) axis. The adrenocortical glucocorticoid hormones cortisol and corticosterone are principal effectors within this circuit since they affect neurotransmission and neuroendocrine control, thus having profound effects on mood and behavior. Using the experimental paradigm of chronic psychosocial stress in tree shrews, we investigated the impact of aversive chronic social encounters on hippocampal structure and function. In chronically stressed animals, we observed dendritic atrophy of hippocampal pyramidal neurons and an impairment of neurogenesis in the dentate gyrus. However, a stress-induced loss of hippocampal neurons was not observed in this animal model. This review summarizes our recent results on structural changes occurring during chronic stress in neurons of the hippocampus and their potential influence on learning and memory. We discuss whether these changes are reversible and to what extent glucocorticoids might be responsible for the stress-induced effects.