Chronic restraint stress inhibits hair growth via substance P mediated by reactive oxygen species in mice

PLoS One. 2013 Apr 26;8(4):e61574. doi: 10.1371/journal.pone.0061574. Print 2013.


Backgrounds: Solid evidence has demonstrated that psychoemotional stress induced alteration of hair cycle through neuropeptide substance P (SP) mediated immune response, the role of reactive oxygen species (ROS) in brain-skin-axis regulation system remains unknown.

Objectives: The present study aims to investigate possible mechanisms of ROS in regulation of SP-mast cell signal pathway in chronic restraint stress (CRS, a model of chronic psychoemotional stress) which induced abnormal of hair cycle.

Methods and results: Our results have demonstrated that CRS actually altered hair cycle by inhibiting hair follicle growth in vivo, prolonging the telogen stage and delaying subsequent anagen and catagen stage. Up-regulation of SP protein expression in cutaneous peripheral nerve fibers and activation of mast cell were observed accompanied with increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in CRS mice skin. In addition, SP receptor antagonist (RP67580) reduced mast cell activations and lipid peroxidation levels as well as increased GSH-Px activity and normalized hair cycle. Furthermore, antioxidant Tempol (a free radical scavenger) also restored hair cycle, reduced SP protein expression and mast cell activation.

Conclusions: Our study provides the first solid evidence for how ROS play a role in regulation of psychoemotional stress induced SP-Mast cell pathway which may provide a convincing rationale for antioxidant application in clinical treatment with psychological stress induced hair loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Chronic Disease
  • Corticosterone / blood
  • Dermis / drug effects
  • Dermis / enzymology
  • Dermis / pathology
  • Glutathione Peroxidase / metabolism
  • Hair / drug effects
  • Hair / growth & development*
  • Hair / metabolism
  • Hair Follicle / drug effects
  • Hair Follicle / growth & development
  • Hair Follicle / pathology
  • Male
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neurokinin-1 Receptor Antagonists
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism*
  • Receptors, Neurokinin-1 / metabolism
  • Restraint, Physical*
  • Stress, Psychological / blood
  • Stress, Psychological / metabolism*
  • Stress, Psychological / pathology*
  • Substance P / metabolism*
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Weight Gain / drug effects


  • Antioxidants
  • Neurokinin-1 Receptor Antagonists
  • Reactive Oxygen Species
  • Receptors, Neurokinin-1
  • Thiobarbituric Acid Reactive Substances
  • Substance P
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Corticosterone

Grant support

This work was supported by the National Natural Science Foundation of China (30900464, 81270316), the Research Program of Soochow University (Q413400111). No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.