F4  NEUROTRANSMITTERS, NEUROPEPTIDES AND NEUROTROPHINS AS REGULATORS OF MURINE HAIR FOLLICLE MOROPHOGENESIS AND CYCLING

¹Peters E. M. J., ²Botchkarev V. A., ²Botchkareva N., ¹ Paus R. ¹Dept. of Dermatology, University Hospital Eppendorf, University of Hamburg, Hamburg, Germany; ²Dept. of Dermatology, Boston University School of Medicine, Boston, MA, USA

Since the nervous system and the hair follicle epithelium share a common ectodermal origin, it is not surprising that clinical as well as experimental observations have long suggested “trophic” interactions between hair follicle innervation and hair follicle development, growth and/or cycling. In this overview we summarize relevant recent data from the C57BL/6 mouse model for hair research and skin neurobiology. Not only the sensory and autonomic skin and hair follicle innervation as well as the skin content for selected neuropeptides and neurotransmitters show striking fluctuations during development and cycling of normal pelage hair follicles, but also neurotrophin and neurotrophin receptor expression and local distribution in defined regions of the follicular epithelium and mesenchym. For example, the number of noradrenaline+ or substance P+ nerve fibers peak in early anagen, with both agents acting as promotors of hair growth in organ-cultured anagen back skin. Moreover, manipulation of the sensory or the autonomic skin innervation can induce a new anagen wave in vivo. Interestingly, the follicular expression of neurotrophins like NT-3 and BDNF as well as of their low and high affinity receptors p75, TrkB, and TrkC peak towards catagen. Data from corresponding knockout or transgenic mice as well as skin organ culture experiments have proven significant neurotrophin effects not only on the development of follicular innervation but also on hair follicle morphogenesis and hair cycling, namely on catagen induction. This suggests that the hair follicle and its innervation act both as source and as a target for neurotransmitters, neuropeptides and neurotrophins and identifies new targets for therapeutic hair growth manipulation by pharmacological interference with these complex pilo-neural interactions.