Dear Editor

Manuscript is important for understanding the pathophysiology of depression. After corrections, I believe the article is ready for publication.Sex-specific contribution of glucocorticoid receptor alpha isoforms to anxiety and depressivelike behavior in mice

1. Introduction
   1.1. Update epidemiological data on depression. Insert updated bibliographic reference.

“ Major depressive disorder (MDD) is one of the most prevalent diseases of the central nervous system and the second leading global cause of disease burden (Lopez et al., 2006)”.

1.2.The authors end the introduction with the conclusion of their study.

“Indeed, our results confirmed that adolescent CUS induced anxiety and depressive-like behavior in adulthood which could be mediated through altered levels of GRα translational isoforms.”

I suggest deleting this conclusion from the end of the introduction.
I believe the end of the introduction should be your research hypothesis.

2.Materials and methods

2.1. Experimental design

• What is the total number of animals used in the research?

-Why was different "n" of animals used in behavioral tests? Do you have any justification?

“ In the first set we estimated changes .... (n=14-15 animals per group)....In the second set of animals we performed tail suspension test (TST) and forced swimming test (FST) (n=8-9animals per group). The third set.... (n=10 animals per group)”.

2.2.Behavioral tests

• Why were animals from the first behavior group used in molecular analysis? Please justify your answer

• Were the behavioral tests performed with an interval of 2 days? (This information is not clear in the text)
  Example: OFT two days later EPMT two days later NSFT

3.Results
3.1.CUS induces anxiety-like behavior

Why were the numbers of animals different between the animal behavior and weight experiments?
These animals were used in protocol 1.

“CUS changes the body weight
“The results of this study shown ...... n=16-17 per group... (Figure 2B)”.

CUS induces anxiety-like behavior
“ In order to determine the effects of CUS on anxiety-like behavior, we performed three tests –OFT, EPM and NSFT. The analysis of OFT... n=14-15 per group..... In the EPM, unstressed females .....n=14-15 per group....
...... However, adolescent stress decreased time spent in open arms.... n=14-15 ..... Finally, stressed animals of both sexes showed increased latency to eat in NSFT (Z=-1.98, n=12-14 per group, p = 0.048 for males; Z=-2.02, n=14 per group, p = 0.043 for females; Figure 2G), and decreased time spent in center of the arena (CUS: F(1,51) = 15.60, n=12-14 per group... Figure 2H).”

3.2.Please review the statistical data and writing (in the results) of figures 3 and 4.

3.3. Supplementary figure 1

Detail the figure's caption.
Only in the cytosol and hippocampus?

3.4.Standardize the writing of the word hippocampus
Hippocampus (HIPPO) or hippo or hippocampus.

“Effects of CUS on GR-responsive genes

“In order to investigate the effect of CUS-induced alterations in GR function in the hippo....”

1. Discussion is extensive and often repetitive.
   Please review the discussion.