Hair growth inhibition by psychoemotional stress: a mouse model for neural mechanisms in hair growth control

Abstract:  Stress has long been discussed controversially as a cause of hair loss. However, solid proof of stress‐induced hair growth inhibition had long been missing. If psychoemotional stress can affect hair growth, this must be mediated via definable neurorendocrine and/or neuroimmunological signaling pathways. Revisiting and up‐dating relevant background data on neural mechanisms of hair growth control, we sketch essentials of hair follicle (HF) neurobiology and discuss the modulation of murine hair growth by neuropeptides, neurotransmitters, neurotrophins, and mast cells. Exploiting an established mouse model for stress, we summarize recent evidence that sonic stress triggers a cascade of molecular events including plasticity of the peptidergic peri‐ and interfollicular innervation and neuroimmune crosstalk. Substance P (SP) and NGF (nerve growth factor) are recruited as key mediators of stress‐induced hair growth‐inhibitory effects. These effects include perifollicular neurogenic inflammation, HF keratinocyte apoptosis, inhibition of proliferation within the HF epithelium, and premature HF regression (catagen induction). Intriguingly, most of these effects can be abrogated by treatment of stressed mice with SP‐receptor neurokinin‐1 receptor (NK‐1) antagonists or NGF‐neutralizing antibodies – as well as, surprisingly, by topical minoxidil. Thus there is now solid in vivo‐evidence for the existence of a defined brain‐ HF axis. This axis can be utilized by psychoemotional and other stressors to prematurely terminate hair growth. Stress‐induced hair growth inhibition can therefore serve as a highly instructive model for exploring the brain‐skin connection and provides a unique experimental model for dissecting general principles of skin neuroendocrinology and neuroimmunology well beyond the HF.