Protein Metabolism Changes and Alterations in Behavior of Trace Amine-Associated Receptor 1 Knockout Mice Fed a High-Fructose Diet

Round 1

Reviewer 1 Report

Thank you very much for allowing me to review the article entitled “Protein metabolism changes and depression-like behavior of trace amine-associated receptor 1 knockout mice fed a high-fructose diet” (neurolint-2219442).

The aim is to study the effect of the TAAR1 gene knockout on the regulation of energy metabolism and depression-like behavior.

The title is informative and fits the content of the work.

The abstract is well structured.

The introduction clearly states the background of the subject and the working hypothesis using adequate bibliography.

The methodology is well described, but in the statistical analysis section, I think it lacks an indication of the correlation test, ratio... applied, which are commented on in the results. As well as the stratification between females and males.

The discussion should raise new stages in this investigation.

The conclusions correspond to the results obtained.

Author Response

Author's Reply to the Review Report (Reviewer 1)

Authors thank to Reviewer for their comments and careful review of our article.

Thank you very much for allowing me to review the article entitled “Protein metabolism changes and

depression-like behavior of trace amine-associated receptor 1 knockout mice fed a high-fructose diet”

(neurolint-2219442).

The aim is to study the effect of the TAAR1 gene knockout on the regulation of energy metabolism and depression-like behavior.

The title is informative and fits the content of the work.

The abstract is well structured.

The introduction clearly states the background of the subject and the working hypothesis using adequate bibliography.

The methodology is well described, but in the statistical analysis section, I think it lacks an indication of the correlation test, ratio... applied, which are commented on in the results. As well as the stratification between females and males.

Two-way analysis of variance (ANOVA) with post-hoc Tukey HSD test was used to compare all biochemical data and behavioral parameters for female knockout mice.

The discussion should raise new stages in this investigation.

The conclusions correspond to the results obtained.

Reviewer 2 Report

Very interesting paper investigating the association between protein metabolism changes and depression-like behavior in mice with high fructose diet. The paper is well-written and of interest for the journal. However, several changes should be made before considering it for publication.

Abstract:

1- The main aim of the paper should be clearly stated in the abstract. The authors reported that TAAR1 knockout mice and WT groups were tested in conditions of a high-fructose diet. Why? Please, explain rationale and aims.

2- At the end of the abstract the authors report that the findings support several hypothesis. A conclusion is needed.

Introduction

1- A figure representing TAAR1 and its association with dopaminergic, serotonergic and glutamatergic activity is needed. 

2- Lines 83. The authors introduce that this protein has been investigated in schizophrenia. In humans? If they want to explain animal and human models, this should be clearly stated. I recommend to explain animal models, and limitations of them, and then human models.

Methods

1- The section 2.1. Animals; should be renamed as Study design.

A table clarifying the methods of the paper would be helpful, including behavioral tests and biochemical parameters.

Discussion

1- More papers should be discussed according to the findings of the paper. I recommend to expand the discussion by adding recent papers.

A limitations and strenghts section is also needed.

Author Response

Author's Reply to the Reviewer 2

Very interesting paper investigating the association between protein metabolism changes and depression-like behavior in mice with high fructose diet. The paper is well-written and of interest for the journal. However, several changes should be made before considering it for publication.

We do appreciate insightful and constructive suggestions of the Reviewer.

Abstract:

1- The main aim of the paper should be clearly stated in the abstract. The authors reported that TAAR1 knockout mice and WT groups were tested in conditions of a high-fructose diet. Why? Please, explain rationale and aims.

Corrected. More details were added to Abstract.

2- At the end of the abstract the authors report that the findings support several hypothesis. A conclusion is needed.

 The conclusion in the end of Abstract has been changed to more сorrect.

Introduction

1- A figure representing TAAR1 and its association with dopaminergic, serotonergic and glutamatergic activity is needed. 

We do appreciate insightful and constructive suggestions of the Reviewer. However, at present we cannot make such a scheme, since it partially refutes the existing relationship between TAAR1 and monoamine systems, and additional studies are required to confirm our hypotheses.

2- Lines 83. The authors introduce that this protein has been investigated in schizophrenia. In humans? If they want to explain animal and human models, this should be clearly stated. I recommend to explain animal models, and limitations of them, and then human models.

In these sentences we are talking about clinical studies that preclinical studies preceded.

The topic of schizophrenia is not the topic of the current article.

Methods

The section 2.1. Animals; should be renamed as Study design.

Corrected.

A table clarifying the methods of the paper would be helpful, including behavioral tests and biochemical parameters.

All methods used in the article are presented in sections, including biochemical, behavioral and statistical methods. The authors ask the Reviewer not to supplement the Methods section with an additional table.

Discussion

1- More papers should be discussed according to the findings of the paper. I recommend to expand the discussion by adding recent papers.                                                                                                                                 

We are grateful to Reviewer for this important suggestion. Recent papers were added to References section.                                                                                                                                

A limitations and strenghts section is also needed.

Limitations and strengths have been discussed in the Discussion section. Limitations and strengths are partly discussed in the discussion. Unfortunately, the relationship between diet and TAAR1 gene knockout has not yet been fully disclosed. Therefore, further experiments are required to understand the problem.