Indications for a brain-hair follicle axis: inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P

It has long been suspected that stress can cause hair loss, although convincing evidence of this has been unavailable. Here, we show that in mice sonic stress significantly increased the number of hair follicles containing apoptotic cells and inhibited intrafollicular keratinocyte proliferation in situ. Sonic stress also significantly increased the number of activated perifollicular macrophage clusters and the number of degranulated mast cells, whereas it down-regulated the number of intraepithelial gamma delta T lymphocytes. These stress-induced immune changes could be mimicked by injection of the neuropeptide substance P in nonstressed mice and were abrogated by a selective substance P receptor antagonist in stressed mice. We conclude that stress can indeed inhibit hair growth in vivo, probably via a substance P-dependent activation of macrophages and/or mast cells in the context of a brain-hair follicle axis.