Psychosocial vs. "physical" stress situations in rodents and humans: role of neurotrophins.

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are well-studied polypeptide growth factors involved in the development and maintenance of specific peripheral and central populations of neuronal cells. In addition to its role as a neurotrophic agent, NGF controls very complex functions in vertebrate physiology. A variety of cells outside the nervous system are in fact able to synthesize NGF including epithelial cells, fibroblasts, lymphocytes, and macrophages. NGF target cells have been identified in the nervous, immune, and endocrine systems, suggesting that NGF may operate through multiple paths to ultimately regulate physiological homeostasis and behavioral coping. We used a mouse model of social stress to demonstrate that NGF levels increase both in plasma and in the hypothalamus following intermale aggressive interactions. The investigation has been extended to other species, including humans, to show that labour, lactation, and the anticipation of the first jump with a parachute also result in increased NGF plasma levels and in changes in the distribution of NGF receptors on lymphocytes. BDNF activation is caused by both physical and social stress events. The aim of this review is to (1) outline the current understanding of the roles of NGF and BDNF in stress-related physiological changes in vertebrates, in particular for physical vs. psychological stressors, which may activate both similar and different neurobiological pathways, and (2) summarize recent efforts to derive pharmacological strategies from the increasing body of BDNF and NGF neurobehavioral data.