PONE-D-23-15624A Study of Roflumilast Treatment on Functional and Structural Changes in Hippocampus in Depressed Adult Male Wistar RatsPLOS ONE

Dear Dr. Hassan,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

This article discusses an interesting point concerning depression behavior which is a common stress disability disorder that affects higher mental functions including emotion, cognition, and behavior. Unfortunately, there are several major concerns raised by the reviewers in the attached documents that will preclude further consideration at this time. We feel that the work is significant and of interest to our readers, and therefore we are willing to consider a thoroughly revised manuscript addressing all of the points raised by the reviewers. Please submit your revised manuscript by Sep 21 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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Abeer El Wakil, PhD

Academic Editor

PLOS ONE

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2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

https://www.sciencedirect.com/science/article/abs/pii/S0014299920305033?via%3Dihub

https://karger.com/cpb/article/31/6/761/71413/Molecular-Mechanisms-of-Depression-Perspectives-on

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: No

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: The idea of the article is interesting, and the manuscript is well written. The experiments are described in sufficient detail. However, a major revision is recommended. Please check the attached file.

Reviewer #2: Need to revise this manuscript before can be accepted.

1. In abstract, anti-apoptotic pathway suggest remove, cause not measured in this study.

2. The positive drug group suppose received drug usually used to treat depression.

3. Please explained from which hemisphere brain was extracted for different methods in this study.

4. Please explain why positive group have elevated immobility and struggle time compared to control group?

5. Please changes the group legend, between positive control and depressed groups. For OFT there was not total number of crossed squares data?

6. Please arrange back the figure for easier to capture the results.

7. Total number of crossed squares results not found in any figure.

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Reviewer #1: No

Reviewer #2: Yes: IDRIS LONG

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Attachments

Attachment

Submitted filename: Comments.docx

Attachment

Submitted filename: PONE-D-23-15624_reviewer-NEW 3.8.pdf

A Study of Roflumilast Treatment on Functional and Structural Changes in Hippocampus in Depressed Adult Male Wistar Rats

PONE-D-23-15624R1

Dear Dr. Hassan,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Abeer El Wakil, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The concept of the present study seems interesting. The aim of the study is to investigate the impact of depression which is a common stress disability disorder affecting higher mental functions including emotion, cognition, and behavior. It may be mediated by inflammatory cytokines that interfere with neuroendocrine function, and synaptic plasticity. Therefore, reductions in inflammation might contribute to treatment response. The current study evaluates the role of Protein Kinase (PKA)- cAMP response element-binding protein (CREB)- brain derived neurotropic factor (BDNF) signaling pathway in depression and the effects of roflumilast (PDE4 inhibitor) as a potential antidepressant on the activity of the PKA-CREB-BDNF signaling pathway, histology,and pro-inflammatory cytokine production.

In my opinion, the concept of the present study is interesting, and the authors addressed the reviewers'concerns thoroughly. The manuscript in its current form is acceptable for publication at Plos One.

Reviewers' comments: