Neurogenic skin inflammation in stress‐triggered inhibition of hair growth in mice is promoted via nerve growth factor‐dependent pathways

Abstract

Recently, we have pointed to the existence of a brain‐hair follicle axis (BFA), with neuropeptide substance P (SP) as one candidate mediator, to which stress‐triggered hair loss is imputable. Based on findings indicating that levels of nerve growth factor (NGF) increase upon exposure to stressful events, which is particularly striking within the context of the BFA, because NGF is known to increase the release of SP, we then aimed at dissecting the role of NGF in stress‐triggered hair loss. We observed increased expression of NGF, analyzed by real time PCR and immunohistochemistry, in stress‐exposed mice with a depilation‐induced hair cycle. Expression of NGF receptor p75 was also upregulated with stress, and TrkA receptor was moderately downregulated. Upon neutralization of NGF by antibody injection, stress‐triggered premature onset of catagen, which was accompanied by apoptosis and increased number/activation of perifollicular mast cells and macrophages, was significantly inhibited. Interestingly, subcutaneous injection of recombinant NGF to mimick stress effects resulted in an increased percentage of SP‐positive neurons in dorsal root ganglia. Taken together, our data indicate that an interactive communication network between sensory nerves and immune cells in the skin is promoted by stress‐triggered release of NGF and results in mast cell activation and migration of macrophages, the release of proinflammatory neuropeptides, i.e. SP. Such disequilibrium, which may be referred to as neurogenic inflammation, constitutes the prerequisite of increased hair loss.