L6 NEUROIMMUNOLOGICAL HAIR GROWTH CONTROL IS STRESS-SENSITIVE: AN OLD PARADIGM REVISITED
Peters EMJ1, Paus R2, Klapp BF1, Arck PC1
1Psychoneuroimmunology, Department of Internal Medicine, Psychosomatics, University-Medicine Charité, Campus Virchow, Humboldt-University of Berlin, Germany
2Department of Dermatology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

Psychosocially, untimely as well as age-related hair loss has dramatic impact on self-esteem and quality of live of those affected. While stress and hair loss have prompted more than one review article in the attempt to collect and analyze the available data, solid proof of any hair growth-inhibitory effect of stressful stimuli had long been missing. But how does stress reach the skin and how can it affect hair growth? Such effects must be mediated via definable neurobiological and/or neuroimmunological signalling pathways. Recent results from a mouse model have shed some light into these questions. Each and every hair follicle is accompanied by a dense nerve fiber network. These nerve fibers, together with nerve fibers in the interfollicular dermis, contain neuropeptides such as substance P (SP) or neurotransmitters such as noradrenaline (NA). Their number and communication with mast cells fluctuates extensively during the hair growth cycle. These changes are of functional relevance to hair growth and a forced increase of SP or NA during hair cycle stages, normally characterized by low expression, can alter hair cycling. Upstream of cutaneous innervation, nerve growth and maintenance in skin is dependent on neurotrophins such as nerve growth factor (NGF), which too is a potent hair growth modulator. A survey of the literature on key candidates in skin-stress responses reveals, that not only NA, the prominent signalling molecule of the sympathetic stress response, but also SP and NGF act as stress-mediators. Moreover, SP and NGF participate in neurogenic inflammation. Accordingly, we could show, that perceived stress increases SP nerve fiber number and NGF expression in murine skin. This is associated with nerve outgrowth as shown by Gap-43-immunoreactivity. During anagen-catagen transition, increased neuro-immune communication leads to perifollicular neurogenic inflammation, apoptosis in hair follicles and premature catagen development. Intriguingly, most of these effects can be neutralized by treatment of stressed mice with SP-receptor NK-1 antagonists or NGF-neutralization - as well as, surprisingly, by topical minoxidil. Together, stress experience can trigger a cascade of molecular events, including plasticity of the peptidergic peri- and interfollicular innervation and neuro-immune crosstalk, during which NGF and SP are recruited as key mediators of stress-induced hair growth-inhibitory effects on the hair follicle. In this highly instructive model neuropeptides, neurotransmitters, neurotrophins and mast cells act as a "central switchboard" of neurogenic inflammation and facilitate exploration of the "brain-skin connection".