LB1017 A novel link between human hair follicle neuroimmunology and mitochondrial biology: Substance P increases intrafollicular oxidative stress and mitochondrial biogenesis

Abstract

Substance P (SP) is the prototypic neuropeptide associated with emotional stress and neurogenic perifollicular inflammation and is released by sensory nerve fibers. It also promotes human hair follicle (HF) immune privilege collapse and catagen development ex vivo, and has thus been implicated in stress-related hair loss, ranging from telogen effluvium to alopecia areata. Since SP stimulates the mitochondrial release of reactive oxygen species, we have asked how SP impacts on human HF mitochondrial biology. When organ-cultured anagen scalp HFs were treated with SP (10-10 and 10-12M), this showed that the mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a key enzymatic marker of oxidative phosphorylation, and mitochondrial activity and biogenesis, was significantly upregulated. This was coupled with significantly increased expression of the mitochondrial mass and biogenesis marker, VDAC1/porin, a channel found in the mitochondrial membrane. SP also significantly increased mTORC1 activity (measured by p-S6 immunofluorescence), a known promoter of ROS production. Since we had previously shown that stress-induced HF greying is associated with VDAC1/porin upregulation, these SP effects suggest a hitherto unknown strong mitochondrial response of human scalp HFs to this stress- and sensory nerve fiber-associated neuropeptide. This invites therapeutic interventions with SP antagonists that target this novel link between mitochondrial biology and neuroimmunology of the HF under conditions of perceived stress in the future management of stress-associated human hair greying and hair loss.