Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction
, Randall Walikonis 3, Ido Carmi 1, Shai Berlin 1 and Andrew P. Levy 1,*
Round 1
Reviewer 1 Report
This is an elegant study with clinical implications for the treatment of both rare diseases associated with pathologic Arf6 hyperactivation, as well as more common disorders such as epilepsy. I would add the following possibility to the discussion, that some of the beneficial changes induced by heat shock are mediated by Sirt3. These include the references below
SIRT3 protects bovine mammary epithelial cells from heat stress damage by activating the AMPK signaling pathway
Cell Death Discovery
7, Article number: 304 (2021
SIRT3 activation promotes enteric neurons survival and differentiation
Scientific Reports 12, Article number: 22076 (2022)
Author Response
We have added a section on the possible role of SIRT1 in the benefit provided by heat therapy to the discussion of the manuscript.
Reviewer 2 Report
In this study the authors used a mouse model to describe the physiological mechanism of beneficial effect of brief heat therapy. It is a well written manuscript with clearly presented methodology. I would only suggest the authors to further explain the possible clinical application of these findings and to further describe the studies which showed a positive effect of prolonged heat therapy on the prevention of AD.
Author Response
We have added in the discussion of the revised manuscript the possible clinical applications of this study with a focus on its potential relevance to AD.
