Systemic Tumors Can Cause Molecular Changes in the Hippocampus That May Have an Impact on Behavior after Chronic Social Stress

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

title can be improved to be more exploratory than informative. or go for something simpler something like systemic tumors can produce molecular changes in the central nervous system that may impact behavior: results from animal models.

in the introduction authors need to give specific gaps in knowledge that this study aims to address.

methods it would be helpful to provide more justification for the specific behavioral tests used and their relevance to the research questions. also, can authors provide refs for experiments where these tests were used and their performance. authors mention that animals were randomly allocated to tumor and non-tumor groups before the start of the chronic social defeat stress (csd) procedure. could you provide more details on how the tumor cells were inoculated and how tumor development was confirmed?

discussion can be improved by discussing the limitations of the study more explicitly and suggesting directions for future research. in the results 3-hk levels and the 3-hk/kyn ratio between tumor-bearing and non-tumor groups. what are mechanisms underlying these differences and their functional significance? also higher ido mrna expression in tumor-bearing animals but no differences in cytokine levels.

 

Author Response

Dear Reviewer, 

Thank you very much for your recommendation and positive feedback. We have carefully addressed here one by one all the issues raised by both reviewers in the attached document.

Yours sincerely, 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Chronic social stress modified hippocampal kynurenine pathway in tumor-bearing male mice

I read the manuscript with interest and the authors can find my appraisal, concerns and recommendations as follows:

Introduction: The introduction is well written, but I recommend to add more information about biochemical underpinnings of stress response. Indeed, this is important for the link between depression and, for example other pathologies. Moreover, the prosocial behavior is important, but the authors need to improve this paragraph, adding more specific info about the association between stress and HPA. According to me, this can halp to improve the manuscript.

Similarly, in stressed animals, the mRNA expression of the monoamines can change. This has also been studied in social stress. I believe that most of the studies involved rats.

I recommend adding a list of abbreviations at the end of the manuscript. This is very useful for the readers.

According to me, the methods are well-written and allow replicability. However, be sure to add all the necessary information included in the checklists for animal studies (i.e. ARRIVE checklist).

Moreover, more info is needed about the resident-intruder paradigm, as well as about PCR procedure.

I agree with the statistical analyses used.

The results are extremely interesting and well-reported.

In the discussion, I recommend to discuss better the IDO immunosuppressive mechanism. Please, add more info about.

 

I recommend adding a brief paragraph about the limitations of the study and indications for future studies. 

Author Response

Dear Reviewer, 

Thank you very much for your recommendation and positive feedback. We have carefully addressed here one by one all the issues raised by both reviewers in the attached document.

Yours sincerely, 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors addressed all my concerns.