B6.1 Nerve growth factor regulates the cutaneous inflammatory response to stress and prematurely terminates murine hair growth

Eva Milena J. Peters ¹, Bori Handjiski ¹, Arne Kuhlmei ¹, Evelin Hagen ¹, Hannes Bielas ¹, Burghard F. Klapp ¹, Ralf Paus ², Petra Clara Arck ¹

¹ Dept. of Internal Medicine, Charité, University Medicine Berlin, Germany; ² Dept. of Dermatology, University Hospital Hamburg Eppendorf, University of Hamburg, Hamburg, Germany.

Recently, we have revealed the existence of a ‘brain-hair follicle axis’ in murine skin and have identified the neuropeptide substance P (SP) as a key mediator of stress-induced hair growth inhibition in vivo. Published evidence indicates that increased numbers of SP-immunoreactive sensory fibres, as we previously described in the dermis of stressed mice, are a result of transient high levels of nerve growth factor (NGF). Further, increased levels of NGF have been described upon stress exposure. Thus, we now aimed at dissecting the role of NGF in stress-triggered hair growth termination. By real time PCR and immunohistochemistry, stress-exposed mice with all back skin hair follicles in the growth phase of the hair cycle (anagen) showed an up-regulation of NGF and its low affinity receptor p75 (a member of the TNF receptor family), while the NGF high affinity receptor tyrosinekinase A (TrkA) was moderately down-regulated. Interestingly, stress produced a similar increased percentage of SP positive neurons in dorsal root ganglia as did subcutaneous NGF-injection. Moreover, stress induced premature onset of catagen, apoptosis of cells in the isthmus and bulge region and in the bulb of hair follicles and increased number/activation of perifollicular mast cells and macrophages, was significantly abrogated by neutralization of NGF in vivo. Taken together, these data suggest that NGF is a central element in the perifollicular neurogenic inflammation that develops during the murine skin response to defined psychoemotional stressors, and that NGF also exerts direct inhibiting effects on hair growth, i.e. directly via p75 or indirectly via SP. Antagonizing NGF-mediated signalling therefore may be a promising therapeutic approach to counter the negative effect of stress on hair growth.