Neurogenic inflammation in stress-induced termination of murine hair growth is promoted by nerve growth factor.
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 suggests that increased numbers of SP-immunoreactive sensory fibers, as seen in the dermis of stressed mice in anagen-catagen transition, are a result of transient high levels of nerve growth factor (NGF). Thus, we now aimed at dissecting the role of NGF in stress-triggered hair growth termination in our murine model. By real time PCR and immunohistochemistry, stress-exposed mice showed an up-regulation of NGF and its low-affinity receptor p75NTR; the NGF high-affinity receptor TrkA was moderately down-regulated. On neutralization of NGF, premature onset of catagen, apoptosis, and increased number/activation of perifollicular mast cells and antigen-presenting cells, which reflects the skin response to stress, was significantly abrogated. Stress or subcutaneous injection of recombinant NGF (to mimic stress) resulted in an increased percentage of SP(+) neurons in dorsal root ganglia, as measured by retrograde tracing. Taken together, these data suggest that NGF is a central element in the perifollicular neurogenic inflammation that develops during the murine skin response to stress and antagonizing NGF may be a promising therapeutic approach to counter the negative effect of stress on hair growth.
Peters
Eva Milena J
EM
Center for Biomedical Research, Charité, University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Handjiski
Bori
B
Kuhlmei
Arne
A
Hagen
Evelin
E
Bielas
Hannes
H
Braun
Armin
A
Klapp
Burghard F
BF
Paus
Ralf
R
Arck
Petra Clara
PC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D005786:Gene Expression Regulation / Q000187:drug effects; D018859:Hair Follicle / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology*; D017879:Isothiocyanates; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012235:Rhodamines; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological / Q000503:physiopathology; D015854:Up-Regulation
D017879:Isothiocyanates; D012235:Rhodamines; D020932:Nerve Growth Factor