O#19   Brain derived neurotrophic factor (BDNF) is expressed in human hair follicles and induces hair follicle regression (catagen)

Eva M. J. Peters1, Marit G. Hansen2, Rupert W. Overall2, Moto Nakamura2, Petra Arck1, Burghard F. Klapp1, Paolo Pertile2 and Ralf Paus2. 1 Dept of Internal Medicin/Psychosomatics, Charite, Humboldt University, Berlin, Germany; 2 Dept of Dermatology, University Hospital-Eppendorf, Hamburg, Germany

Brain derived neurotrophic factor (BDNF) and its high affinity receptor tyrosine kinase B (TrkB) are expressed by peripheral innervation targets such as the hair follicle. In murine hair follicle cycling BDNF signalling appears to play an important role in catagen development. However, nothing is known on human hair growth effects. Here, we show by RT-PCR and immunohistochemical that BDNF and TrkB are expressed on both the gene and protein level in human scalp hair follicles. BDNF immunoreactivity was strongest in the proximal inner root sheath and present in the dermal papilla of anagen VI hair follicles. TrkB-immunoreactivity, was strongest in the basal layer of the distal outer root sheath, positive in the proximal inner and outer root sheath, and negative in the dermal papilla of anagen VI hair follicles. In contrast BDNF was expressed in the hair follicle epithelium of telogen hair follicles, but not in telogen dermal papilla, while only faint epithelial expression could be observed with TrkB. In cultured human scalp skin anagen hair follicles BDNF significantly inhibited hair shaft elongation over a culture period of 10 days. Histomorphometric analysis showed that most hair follicles treated with BDNF (50 ng/ml) had entered a catagen-like stage, while the majority of control hair follicles remained in anagen VI (p-value…). Analysis of TUNEL+ (i.e. apoptotic cells) and Ki67+ (i.e. proliferating cells) after 10 days in culture revealed significantly decreased proliferation in hair bulbs treated with 50 ng/ml BDNF. Also, light cycler PCR demonstrated upregulation of TGFb II transcripts steady state levels by treatment with 50 ng/ml BDNF after 48h. These results suggest mesenchymal-epithelial cross-talk between the BDNF-excreting dermal papilla and the TrkB+ hair matrix in anagen hair follicles, which is likely to be involved in the orchestration of hair follicle regression.