Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with hyperactivation of mTOR signaling pathway. Previously, we have reported that GSK3β signaling was involved in sweating　(Matsui S et al J Invest Dermatol 2014).  More recent report suggested that hyperactivation of mTOR signaling pathway also downregulates melanin synthesis through alteration of GSK3β signaling. However, that whether mTOR, the upstream of GSK3β, was also involved in sweating, is still unknown.  To investigate whether the sweating function was impaired in TSC patients, and to further elucidate whether m-TOR was responsible for sweating dysfunction. 
   The sweating function of patients with TSC and healthy donors were measured by Qsart (SKN−2000, Nishizawa, Japan). And using TSC model mice and wild-type mice, sweating in mice footpads were induced by local acetylcholine injection, and then sweat volume was evaluated by starch-iodine reaction. Furthermore, mTOR signaling was assessed in mice tissues from footpads by immunohistochemical staining. Finally, rapamycin gel (0.2%) were applied to mice footpads, the alterations of sweating function and mTOR siganling were also examined.
  Decreased sweating was found in TSC patient and TSC model mice.
The decreased intracellular filaments were found in the TSC myoepithelial cells of sweat glands.
  Rapamycin improved the decreased sweating in TSC model, it suggested that TSC-mTOR signaling pathway might be involved in these processes.

Morphological and functional analysis on M3R mediated sweating in TSC1 k/o mouse