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 convin cing evidence of this has been unavailable. Here, we show that in mice soni c stress significantly increased the number of hair follicles containing ap optotic cells and inhibited intrafollicular keratinocyte proliferation in s itu. Sonic stress also significantly increased the number of activated peri follicular macrophage clusters and the number of degranulated mast cells, w hereas it down-regulated the number of intraepithelial gamma delta T lympho cytes. These stress-induced immune changes could be mimicked by injection o f the neuropeptide substance P in nonstressed mice and were abrogated by a selective substance P receptor antagonist in stressed mice. We conclude tha t 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.