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

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Cell Death Discovery 

volume 7, Article number: 304 (2021

SIRT3 activation promotes enteric neurons survival and differentiation

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Scientific Reports volume 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.