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Mast cell deficient and neurokinin-1 receptor knockout mice are protected from stress-induced hair growth inhibition

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Abstract

Despite the lack of insight on distinct mediators in the skin orchestrating the pathophysiological response to stress, hair loss has often been reported to be caused by stress. Recently we revealed the existence of a “brain-hair follicle axis” by characterizing the neurokinin (NK) substance P (SP) as a central element in the stress-induced threat to the hair follicle, resulting in premature onset of catagen accompanied by mast cell activation in the skin. However, our understanding of possible SP–mast cell interactions in the skin in response to stress was limited since the receptor by which SP activates skin mast cells and the extent of mast cell mediated aggravation of SP remained to be elucidated. We now employed NK-1 receptor knockout mice (NK-1R−/−) and mast cell deficient W/Wv mice and observed that stress-triggered premature induction of catagen and hair follicle apoptosis does not occur in NK1−/− and W/Wv mice. Furthermore, the activation status of mast cells was less in stressed NK1−/− mice than in wild-type control. Additionally, stress-induced upregulation of SP positive nerve fibers was absent in both NK-1R and W/Wv mice. These results indicate that the cross-talk between SP and mast cell activation via NK-1R appears to be the most important pathway in the regulation of hair follicle cycling upon stress response.

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Abbreviations

CRF :

Corticotropin-releasing factor

NGF :

Nerve growth factor

NK-1R :

Neurokinin 1 receptor

SP :

Substance P

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Acknowledgements

This work was supported by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft, Ar 232/14-1, Pa 345/11-1) and Charité (UFF 99-648). We thank R. Pliet, E. Hagen, P. Moschansky, and P. Busse for their excellent technical assistance.

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Authors and Affiliations

  1. Biomedizinisches Forschungszentrum, Campus Virchow Klinikum, Charité University Medicine, Augustenburger Platz 1, 13353, Berlin, Germany

    Petra C. Arck, Bori Handjiski, Arne Kuhlmei, Eva M. J. Peters, Anita Peter & Burghard F. Klapp

  2. Department of Pediatrics, Charité University Medicine, Augustenburger Platz 1, 13353, Berlin, Germany

    Maike Knackstedt

  3. Department of Anatomy and Developmental Biology, University College London, London, UK

    Stephen P. Hunt

  4. Department of Dermatology, University Hospital Eppendorf, Hamburg, Germany

    Ralf Paus

Authors
  1. Petra C. Arck
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  2. Bori Handjiski
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  3. Arne Kuhlmei
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  4. Eva M. J. Peters
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  5. Maike Knackstedt
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  6. Anita Peter
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  8. Burghard F. Klapp
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  9. Ralf Paus
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Correspondence to Petra C. Arck.

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Arck, P.C., Handjiski, B., Kuhlmei, A. et al. Mast cell deficient and neurokinin-1 receptor knockout mice are protected from stress-induced hair growth inhibition. J Mol Med 83, 386–396 (2005). https://doi.org/10.1007/s00109-004-0627-z

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  • DOI: https://doi.org/10.1007/s00109-004-0627-z

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