P5.49 INDUCTION OF NEUROPEPTIDES IN SKIN INNERVATING SENSORY NEURONS BY STRESS AND NERVE GROWTH FACTOR AS A POSSIBLE REASON FOR HAIR GROWTH ALTERATION

A. Kuhlmei¹, Q.T. Dinh¹, E.M.J. Peters¹, J. Kandil¹, R. Paus², B.F. Klapp¹, P.C. Arck¹

¹Department of Internal Medicine, Charité, University Medicine Berlin, Germany ²Department of Dermatology, University Hospital Eppendorf, Hamburg, Germany

Recently, we introduced a mouse model to launch experimental evidence for stress-induced hair growth inhibition (HGI), pointing to the existence of a ‘brain-hair follicle axis (BFA)’. We suggested that nerve growth factor (NGF), besides neuropeptide substance P (SP), are candidate mediators along the BFA. Published data further indicate that stress related neuropeptides, e.g. calcitonin gene related peptide (CGRP) and SP may be involved in HGI. SP and CGRP are synthesized in dorsal root ganglia (DRG) and released after axonal transport in the skin. Thus, the aim of the present study was to investigate the effect of stress or subcutaneous injection of NGF, which mimicks stress and regulates neuropeptide genes in sensory neurons, on the expression of SP and CGRP in DRG.

Anagen was induced in C57BL/6 mice by depilation and retrograde tracing was employed on day 9 post depilation (pd). On day 14 pd, mice were either exposed to sound stress (n=4), injected subcutaneously with NGF (n=4) or served as controls (n=4). On day 16 pd, DRG (mean of 30/mouse) were harvested and SP and CGRP in skin specific sensory neurons, as identified by the tracer dye, were labelled by immunohistochemistry and counted double blindly.

Stress exposure as well as NGF injection leads to a significant induction of SP and CGRP in retrograde labelled neurons. Moreover, stress induced premature onset of catagen and an increased percentage of SP and CGRP positive dermal nerve fibres. This allows us to conclude that sensitive dermal nerve fibres are likely to originate from the presently identified neuropeptide-positive neurons. Peripheral activation of SP-expressing afferent nerve fibres via NGF-dependent pathways may cause neurogenic inflammation, eventually resulting in HGI.