The Role and Mechanisms of the Hypocretin System in Zebrafish (Danio rerio)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Manuscript title:

 Orexin System of Zebrafish, Danio rerio

 

 Dyachuk V.A.

This review article is an interesting topic, and the author explains that zebrafish is a model for studying the hypocretin (orexin) system and its physiological roles.

The text is confused with orexin or hypocretin words. The author must stick with one name.

The figure legends should have one pattern of abbreviation – alphabetical order. Now, it is irregularly arranged.

The references do not follow the journal criteria.

In the second paragraph of page 2, there are mistakes with the PDF conversion.

Page 6, lines 216 and 217. Hypocretin pathology in human narcolepsy. The references are Peyron et al. 2000 and Thannickal et al. 2000.  Sakurai and Scammell to be removed.

 

 

The article ended without a conclusion.

Author Response

Rev 1

Dyachuk V.A.

This review article is an interesting topic, and the author explains that zebrafish is a model for studying the hypocretin (orexin) system and its physiological roles.

The text is confused with orexin or hypocretin words. The author must stick with one name.

Reply:

Thank you for your comment. We have brought everything to uniformity as hypocretin/

The figure legends should have one pattern of abbreviation – alphabetical order. Now, it is irregularly arranged.

Reply:

Done

The references do not follow the journal criteria.

Reply:

Changed

In the second paragraph of page 2, there are mistakes with the PDF conversion.

Reply:

Sorry for this technical error. Fixed

Page 6, lines 216 and 217. Hypocretin pathology in human narcolepsy. The references are Peyron et al. 2000 and Thannickal et al. 2000.  Sakurai and Scammell to be removed.

Reply:

Deleted

The article ended without a conclusion.

Reply:

I have added the conclusion in the end of MS.

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript "Orexin System of Zebrafish, Danio rerio“ explores on significance of Danio rerio as a model to study the functions of hypocretin neural networks and their functions. It has been frequently reported that the orexin/hypocretin (ORX) system is involved in various physiological processes as well as in the control of sleep and wakefulness. Studies have speculated that ORX system may drive the aminergic and cholinergic activities that control sleep and wakefulness states. However, the biological mechanisms and relevance of the interactions between the neurotransmitter systems are poorly understood. The submitted manuscript, analyzing the available literatures, explores these aspects to some extent.

After going through the manuscript, I have following comments for the authors.

1.     I would suggest the authors to elaborately discuss the cholinergic and aminergic input to the ORX system.

2.     The manuscript needs to be structured: The introduction is bulky, the objective of the study is mentioned neither in the manuscript nor in the text. The abstract also needs restructuring, it is composed so that the interpreted results are not from external studies but from own experiments. Conclusion is also missing.

3.     The title of the manuscript does not reflect the spectrum of the study. It should be something meaningful (eg. The Role and Mechanisms of the Orexin System in Zebrafish (Danio rerio) or Exploring the Orexin System in Zebrafish (Danio rerio): Functional Insights and Implications, …….)

 

Comments on the Quality of English Language

Improvement of the language including grammatical corrections and syntax adjustments suggested.

Author Response

Rev 2

The manuscript "Orexin System of Zebrafish, Danio rerio“ explores on significance of Danio rerio as a model to study the functions of hypocretin neural networks and their functions. It has been frequently reported that the orexin/hypocretin (ORX) system is involved in various physiological processes as well as in the control of sleep and wakefulness. Studies have speculated that ORX system may drive the aminergic and cholinergic activities that control sleep and wakefulness states. However, the biological mechanisms and relevance of the interactions between the neurotransmitter systems are poorly understood. The submitted manuscript, analyzing the available literatures, explores these aspects to some extent.

After going through the manuscript, I have following comments for the authors.

1. I would suggest the authors to elaborately discuss the cholinergic and aminergic input to the ORX system.

Reply

I added a paragraph about the role the cholinergic and aminergic input to the ORX system

2. The manuscript needs to be structured: The introduction is bulky, the objective of the study is mentioned neither in the manuscript nor in the text. The abstract also needs restructuring, it is composed so that the interpreted results are not from external studies but from own experiments. Conclusion is also missing.

Reply

We have performed textual changes

3. The title of the manuscript does not reflect the spectrum of the study. It should be something meaningful (eg. The Role and Mechanisms of the Orexin System in Zebrafish (Danio rerio) or Exploring the Orexin System in Zebrafish (Danio rerio): Functional Insights and Implications, …….)

Reply

Changed

Comments on the Quality of English Language

Improvement of the language including grammatical corrections and syntax adjustments suggested.

Reply

Verified by a native speaker

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript "Orexin System of Zebrafish, Danio rerio" is not structured, and its format does not permit evaluation. Page 2 is impossible to read. Please revise the manuscript to be evaluated.

Comments on the Quality of English Language

The English is good.

Author Response

Rev3

Comments and Suggestions for Authors

The manuscript "Orexin System of Zebrafish, Danio rerio" is not structured, and its format does not permit evaluation. Page 2 is impossible to read. Please revise the manuscript to be evaluated.

Comments on the Quality of English Language

The English is good.

Reply

Thanks for the comments. We have corrected page 2 and made the appropriate textual changes

Reviewer 4 Report

Comments and Suggestions for Authors

The manuscript entitled “Orexin System of Zebrafish, Danio rerio” discusses the insights of the overexpression of the hcrt gene in Danio larvae causes wakefulness, whereas physical destruction of HCRT cells or pharmacological blockade of the type 2 orexin receptor leads to fragmentation of sleep in fish larvae, which is also observed in patients with narcolepsy. The presented data confirm the conservatism of the orexin system. The review is well-written and I recommend for publication after minor revision.

 

The below revisions are recommended:

 

1. The title does not sound meaningful. It does not reflect the materials that have been discussed in the manuscript. I recommend to revise the title meaningfully.

 

2. There are many reports in the literature that include similar research objectives. Cite some recent reports in the manuscript.

 

3. The manuscript must be thoroughly checked, and the quality of the language must be improved. There are numerous grammatical mistakes.

 

4. Uniformity (font and size) should be mentioned throughout the manuscript, including the schemes and figures. The authors are encouraged to check the journal IFA. 

Author Response

Rev4

The manuscript entitled “Orexin System of Zebrafish, Danio rerio” discusses the insights of the overexpression of the hcrt gene in Danio larvae causes wakefulness, whereas physical destruction of HCRT cells or pharmacological blockade of the type 2 orexin receptor leads to fragmentation of sleep in fish larvae, which is also observed in patients with narcolepsy. The presented data confirm the conservatism of the orexin system. The review is well-written and I recommend for publication after minor revision.

 

The below revisions are recommended:

1. The title does not sound meaningful. It does not reflect the materials that have been discussed in the manuscript. I recommend to revise the title meaningfully.

Reply

We have changed the title of the MS “The Role and Mechanisms of the Hypocretin System in Zebrafish (Danio rerio)

1. There are many reports in the literature that include similar research objectives. Cite some recent reports in the manuscript.

Reply

Done

 

1. The manuscript must be thoroughly checked, and the quality of the language must be improved. There are numerous grammatical mistakes.

Reply

Verified by a native speaker

 

1. Uniformity (font and size) should be mentioned throughout the manuscript, including the schemes and figures. The authors are encouraged to check the journal IFA

Reply

Done

Reviewer 5 Report

Comments and Suggestions for Authors

I my opinion  this MS is very interesting and important because it describes a model fish, and the research can be translated to mammals, including humans. The study concerns the role of the orexin system (HCRT) in the regulation of sleep and wakefulness and the use of the fish Danio rerio as a research model for the analysis of the function of orexin neurons, the disruption of which leads to diseases such as narcolepsy and cataplexy. The author indicated that Danio rerio, due to the similarities in the structure of the HCRT system to mammals, is an excellent model for the analysis of sleep mechanisms and disorders related to it.

I believe that these studies are of great practical importance, because understanding the function and disorders of the orexin system in a model such as Danio rerio. These studies may contribute to the development of new therapies for the treatment of narcolepsy and other sleep disorders, also in humans. However, the MS contains some editing errors, which I have noted in the text.

Comments for author File: Comments.pdf

Author Response

Rev5

I my opinion  this MS is very interesting and important because it describes a model fish, and the research can be translated to mammals, including humans. The study concerns the role of the orexin system (HCRT) in the regulation of sleep and wakefulness and the use of the fish Danio rerio as a research model for the analysis of the function of orexin neurons, the disruption of which leads to diseases such as narcolepsy and cataplexy. The author indicated that Danio rerio, due to the similarities in the structure of the HCRT system to mammals, is an excellent model for the analysis of sleep mechanisms and disorders related to it.

I believe that these studies are of great practical importance, because understanding the function and disorders of the orexin system in a model such as Danio rerio. These studies may contribute to the development of new therapies for the treatment of narcolepsy and other sleep disorders, also in humans. However, the MS contains some editing errors, which I have noted in the text.

Reply

Thank you so much for the comments and edits to the text. Thank you for your time spent on the text. This is very valuable and important for us. Thank you so much. Your edits are all taken into account

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

ijms-3328162

 

Title: The role and mechanisms of the hypocretin system in Zebrafish (D.rerio)

Author: Dyachuh V.A.

 

The revised manuscript changed according to suggestions.

There are a few things to consider :

The abbreviation used for hypocretin is not uniform in the text

HCRT, Hcrt. It should be uniform in the text.

Line 99: HcrtR receptor

Receptor is repetition

Line 166: 3-neurons

It is GnRH3 -neurons

Line 201: HcrtR receptor

Receptor is repetition

Line 305: HCR-1 has to correct

Line 310: HRT has to correct

Line 318: Riske -K2 has to correct

 

Reference 22 is not in the text.

Comments on the Quality of English Language

The quality of the language is to be improved.

Author Response

Reviewer 1

The revised manuscript changed according to suggestions.

There are a few things to consider :

The abbreviation used for hypocretin is not uniform in the text

HCRT, Hcrt. It should be uniform in the text.

Line 99: HcrtR receptor

Receptor is repetition

Line 166: 3-neurons

It is GnRH3 -neurons

Line 201: HcrtR receptor

Receptor is repetition

Line 305: HCR-1 has to correct

Line 310: HRT has to correct

Line 318: Riske -K2 has to correct

Reference 22 is not in the text.

Comments on the Quality of English Language

Te quality of the language is to be improved.

Reply

Dear reviewer!Thank you so much for such a thorough reading and detection of typos and errors in the text. All your comments have been taken into account and corrected by me.

1)The contractions of receptors and ligands are brought to uniformity

2) Added a link

3) fixed molecules

4)fixed typos in the text

5) English is verified by a native speaker

Thank you for your time and for checking the text so thoroughly.

Author

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for doing necessary corrections. I am happy with this version.

Author Response

Reviewer 2

Thank you for doing necessary corrections. I am happy with this version.

Reply

Thank you so much

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript "The Role and Mechanisms of the Hypocretin System in
Zebrafish (Danio rerio)" is well written.

1. The research examines the advantages of utilizing zebrafish while neglecting to consider potential disadvantages, like the lack of certain human-like intricacies in their hypocretin systems.

2. Please enhance figures with clearer annotations and align them more closely with the textual content.

3. To clarify, expand the discussion on the functional heterogeneity of HCRT neurons with a more in-depth analysis of existing literature.

I recommend a minor revision.

Author Response

Reviewer 3

The manuscript "The Role and Mechanisms of the Hypocretin System in
Zebrafish (Danio rerio)" is well written.

1. The research examines the advantages of utilizing zebrafish while neglecting to consider potential disadvantages, like the lack of certain human-like intricacies in their hypocretin systems.
2. Please enhance figures with clearer annotations and align them more closely with the textual content.
3. To clarify, expand the discussion on the functional heterogeneity of HCRT neurons with a more in-depth analysis of existing literature.

I recommend a minor revision.

Reply

Dear reviewer. Thank you for your comments.

We added more information and drew attention to the shortcomings of the zebrafish model and the heterogeneity of neurons in short, because this can be a discussion and the subject of a separate article.

Reviewer 5 Report

Comments and Suggestions for Authors

In my opinion MS is very interesting and can be published in its current form.

Author Response

Reviewer 5

In my opinion MS is very interesting and can be published in its current form.

Reply

Thank you so much