Oxidative Stress Mediates Autophagy Plays A Role In Chronic Restrained Stress Induced The Delay Of Anagen In C57BL/6Mice

Purpose: Neuropeptide substance P (SP) and reactive oxygen species (ROS) havebeen demonstrated to play an important role in psychological stress induced alteration ofhair cycle, the underlying mechanism remains unknown. The present study aims toinvestigate possible contribution of SP and ROS in chronic restraint stress (CRS, a chronicpsychological stress model) induced abnormal of hair cycle and induction of autophagy.Methods:A chronic restrained stress (CRS) model is employed in this study.The miceare randomly divided into the following groups:(1) Control group;(2) CRS group: nodrug injection and application of CRS;(3) Tempol group: application of CRS concomitantwith intraperitoneal injection of Tempol;(4) Substance P receptor (NK1) blocker, RP67580group:application of CRS concomitant with intraperitoneal injection of RP67580.Anagenof mice dorsal hair follicles was induced by depilation.The CRS model is estimated by thebody weight gains,move distances and stands,as well as the plasma corticosteronelevel.Degrees of oxidative stress is determined by thiobarbituric acid reactive substances(TBARS) levels, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)activity in skin. The grayscale of mice dorsal skin is help to judge repres the hair folliclescycle.Autophagy is measured by the expression of LC3-B, the marker protein ofautophagy.Results: Our results revealed that CRS reduced body weight gain, move distance andstands, affected hair cycle by prolonging the telogen stage and delaying subsequent anagenand catagen stage. CRS resulted in increase of lipid peroxidation levels and reduction ofthe activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and theincrease of autophagy marker (microtubule-associated proteins, light chain3-B, LC3-B) inmice skin. Treatment with antioxidant Tempol (a free radical scavenger) restored GSH-Pxactivity, and significantly reduced increases of lipid peroxidation levels and LC3-Bexpression, as well as normalized hair cycle. In addition, a SP receptor (NK1) antagonist (RP67580) also restored SOD and GSH-Px activities, and markedly reduced increases oflipid peroxidation levels and LC3-B expression, and normalized hair cycle.Conclusion:：Our study provides the first strong evidence for SP and ROS play a rolenot only in alteration of hair cycle also in induction of autophagy levels in psychologicalstress model.