The low and high doses administration of lutein improves memory and synaptic plasticity impairment through different mechanisms in a rat model of vascular dementia

Hamideh Asadi nejad; Amirhossein Yousefi Nejad; Somayeh Akbari; Maryam Naseh; Seyed Mostafa Shid Moosavi; Masoud Haghani

doi:10.1371/journal.pone.0302850

Peer Review History

Original SubmissionJanuary 3, 2024
12 Feb 2024 Decision Letter - Vara Prasad Saka, Editor PONE-D-24-00251The low and high doses administration of lutein improves memory and synaptic plasticity impairment through different mechanisms in a rat model of vascular dementiaPLOS ONE Dear Dr. Haghani, 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. Please submit your revised manuscript by Mar 28 2024 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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The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: https://pubmed.ncbi.nlm.nih.gov/32916222/ https://onlinelibrary.wiley.com/doi/10.1002/brb3.3351 https://pubmed.ncbi.nlm.nih.gov/34116172/ In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. 3. In your Methods section, please report the source of Lutein used for your study. 4. To comply with PLOS ONE submissions requirements, in your Methods section, please provide additional information regarding the experiments involving animals and ensure you have included details on (1) methods of sacrifice, (2) methods of anesthesia and/or analgesia, and (3) efforts to alleviate suffering. 5. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 6. Thank you for stating the following in the Acknowledgments Section of your manuscript: “The authors acknowledge the Research Council of Shiraz University of Medical Sciences, Shiraz, Iran for the financial support of this study (Grant Number: 26316), as a thesis of Mrs. Asadi nejad for acquiring M.Sc. degree in physiology.” We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “The author(s) received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 7. In this instance it seems there may be acceptable restrictions in place that prevent the public sharing of your minimal data. However, in line with our goal of ensuring long-term data availability to all interested researchers, PLOS’ Data Policy states that authors cannot be the sole named individuals responsible for ensuring data access (http://journals.plos.org/plosone/s/data-availability#loc-acceptable-data-sharing-methods). Data requests to a non-author institutional point of contact, such as a data access or ethics committee, helps guarantee long term stability and availability of data. Providing interested researchers with a durable point of contact ensures data will be accessible even if an author changes email addresses, institutions, or becomes unavailable to answer requests. Before we proceed with your manuscript, please also provide non-author contact information (phone/email/hyperlink) for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If no institutional body is available to respond to requests for your minimal data, please consider if there any institutional representatives who did not collaborate in the study, and are not listed as authors on the manuscript, who would be able to hold the data and respond to external requests for data access? If so, please provide their contact information (i.e., email address). Please also provide details on how you will ensure persistent or long-term data storage and availability. 8. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments: I congratulate the authors for the extensive work which might add value to the scientific community. Although the manuscript is good, there are some minor revisions to be made. Thank you. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The study is novel. The study is accordance with research and publication ethics. They have clearly mentioned about their methodology, ethical clearance and statistical data of evaluation and conclusion is in accordance with the aim of the study. Reviewer #2: I have had the opportunity to review your manuscript, I must commend you on your interesting investigation into the effects of lutein administration in a rat model of bilateral-carotid vessel occlusion, particularly focusing on spatial and fear memory, synaptic plasticity, and hippocampal cells. Your study addresses an important area of research, and your findings have the potential to contribute significantly to our understanding of the therapeutic potential of lutein in vascular dementia. However, I have some queries and suggestions that I believe need to be addressed before the manuscript can be considered for publication. 1. Were the doses of lutein chosen for this study based on previous research? Can you provide more details about the rationale behind choosing the doses of 0.5mg/kg and 5mg/kg for lutein administration? 2. Could you please clarify whether your study adhered to the ARRIVE guidelines for reporting animal research? Ensuring compliance with these guidelines is essential for transparency and reproducibility in animal studies. 3. Could the authors please provide information on the age of the rats selected for this study? Clarifying the age range of the experimental animals is important for understanding the developmental stage at which the interventions were applied and interpreting the study findings accurately. 4. Were there any limitations or challenges encountered during the experimental procedures or data analysis that could have influenced the study outcomes? 5. Based on the findings of this study, what are the potential implications for future research or clinical applications related to lutein administration in vascular dementia (VD) patients? ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Nutakki Tulasi Uma Rani Reviewer #2: Yes: Dr. Rukaiah Fatma Begum ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0302850.r001
Revision 1
20 Mar 2024 Author Response Dear Editor and Reviewers, We highly appreciate the detailed valuable comments of the referees on our manuscript of ‘ONE-D-24-00251’. The suggestions are quite helpful for us and we incorporate them in line with your suggestions and those of the reviewers. The following responses have been prepared to address all comments in a point–by–point fashion and we hope the Reviewers and the Editors will be satisfied with our responses to the comments and the revisions for the original manuscript. Any change to the manuscript has been highlighted by using track changes colored text. Journal requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates We have revised the manuscript to comply with PLOS ONE's style requirements. 2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: https://pubmed.ncbi.nlm.nih.gov/32916222/ https://onlinelibrary.wiley.com/doi/10.1002/brb3.3351 https://pubmed.ncbi.nlm.nih.gov/34116172/ In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. We have corrected the minor overlapping, we also would like to clarify that the overlap is confined to the methods section, and we have appropriately cited all relevant sources, the three studies are related to our team's previous research. We appreciate your attention to this matter. 3. In your Methods section, please report the source of Lutein used for your study. Thank you, we have added the source of Lutein in method section 4. To comply with PLOS ONE submissions requirements, in your Methods section, please provide additional information regarding the experiments involving animals and ensure you have included details on (1) methods of sacrifice, (2) methods of anesthesia and/or analgesia, and (3) efforts to alleviate suffering. We have incorporated the following details into the Methods section: To alleviate animal suffering, all animals euthanized at end of the experiment, following induction of deep anesthesia with urethane, rats were sacrificed using a guillotine. The personnel responsible for sacrifice were trained in the humane and ethical handling of animals, and the procedures were conducted in compliance with the Institutional Ethics Committee of Shiraz University of Medical Sciences. 5. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. Thank you, The Research Council of Shiraz University of Medical Sciences, Shiraz, Iran, financially supported this study (Grant Number: 26316), as a thesis of Mrs. Asadi nejad for acquiring M.Sc. degree in physiology. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. Thank you; we have also provided an explanation of the grant information in the cover letter. 6. Thank you for stating the following in the Acknowledgments Section of your manuscript: “The authors acknowledge the Research Council of Shiraz University of Medical Sciences, Shiraz, Iran for the financial support of this study (Grant Number: 26316), as a thesis of Mrs. Asadi nejad for acquiring M.Sc. degree in physiology.” We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “The author(s) received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Thank you once again. We have omitted the funding information from the Acknowledgments section and have also provided a detailed explanation in the cover letter. 7. In this instance it seems there may be acceptable restrictions in place that prevent the public sharing of your minimal data. However, in line with our goal of ensuring long-term data availability to all interested researchers, PLOS’ Data Policy states that authors cannot be the sole named individuals responsible for ensuring data access (http://journals.plos.org/plosone/s/data-availability#loc-acceptable-data-sharing-methods). Data requests to a non-author institutional point of contact, such as a data access or ethics committee, helps guarantee long term stability and availability of data. Providing interested researchers with a durable point of contact ensures data will be accessible even if an author changes email addresses, institutions, or becomes unavailable to answer requests. Before we proceed with your manuscript, please also provide non-author contact information (phone/email/hyperlink) for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If no institutional body is available to respond to requests for your minimal data, please consider if there any institutional representatives who did not collaborate in the study, and are not listed as authors on the manuscript, who would be able to hold the data and respond to external requests for data access? If so, please provide their contact information (i.e., email address). Please also provide details on how you will ensure persistent or long-term data storage and availability. We understand the importance of data availability and appreciate the guidance provided by PLOS' Data Policy. To ensure long-term stability and availability of the data, we established a data access point within our institution. We provided contact details, including phone/email, for our data access committee with following addresses: Mrs Masoumi, phone number +987132302026 E-mail: medphyzio1@sums.ac.ir We recognize the necessity for a durable point of contact, and we assure you that the provided information will guarantee accessibility to the data even in the case of changes in authors' contact details or availability. Thank you for your understanding, and we provided the required non-author contact information. 8. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Thank you for the feedback. I have thoroughly reviewed the reference list, ensuring its completeness and correctness. Additional Editor Comments: Reviewer #1: The study is novel. The study is accordance with research and publication ethics. They have clearly mentioned about their methodology, ethical clearance and statistical data of evaluation and conclusion is in accordance with the aim of the study. Thank you for sharing the positive feedback about the study. It's great to hear that the study is considered novel and aligns well with research and publication ethics. The clarity in methodology, ethical clearance, and the appropriate presentation of statistical data is crucial for ensuring transparency and reliability in research. If you have any specific questions or if there are additional aspects, you'd like us to address, please feel free to let us know. We appreciate your positive assessment. Reviewer #2: I have had the opportunity to review your manuscript, I must commend you on your interesting investigation into the effects of lutein administration in a rat model of bilateral-carotid vessel occlusion, particularly focusing on spatial and fear memory, synaptic plasticity, and hippocampal cells. Your study addresses an important area of research, and your findings have the potential to contribute significantly to our understanding of the therapeutic potential of lutein in vascular dementia. However, I have some queries and suggestions that I believe need to be addressed before the manuscript can be considered for publication. Thank you for your positive feedback on the study's significance and potential contribution to understanding the therapeutic effects of lutein in vascular dementia. I appreciate your diligence in reviewing the manuscript. 1. Were the doses of lutein chosen for this study based on previous research? Can you provide more details about the rationale behind choosing the doses of 0.5mg/kg and 5mg/kg for lutein administration? The selection of lutein doses in this study was based on previous research findings and considerations related to the potential therapeutic effects of lutein. The rationale for choosing the specific doses of 0.5mg/kg and 5mg/kg is rooted in existing literature that suggests a range of effective concentrations for lutein interventions in various experimental settings. These doses were selected to encompass a lower and higher range within this effective concentration spectrum, allowing the researchers to observe potential dose-dependent effects and evaluate the optimal dosage for the intended outcomes. The decision was also influenced by safety considerations and previous studies that demonstrated beneficial effects within similar dose ranges. 2. Could you please clarify whether your study adhered to the ARRIVE guidelines for reporting animal research? Ensuring compliance with these guidelines is essential for transparency and reproducibility in animal studies. Thank you for your comment. We have thoroughly reviewed our study and can confirm that it adheres to the ARRIVE guidelines for reporting animal research. Additionally, we would like to inform you that ethical approval was obtained, and the study was conducted in accordance with the guidelines provided by the Institutional Animal Ethics Committee under the ethical code IR.SUMS.AEC.1401.077. The revised manuscript now explicitly mentions this ethical approval to enhance transparency and compliance with ethical standards. 3. Could the authors please provide information on the age of the rats selected for this study? Clarifying the age range of the experimental animals is important for understanding the developmental stage at which the interventions were applied and interpreting the study findings accurately. Thank you for this comment we added detail of age as follow: Adult male Sprague Dawley rats (250-300 g, aged 7-10 weeks) were housed under … 4. Were there any limitations or challenges encountered during the experimental procedures or data analysis that could have influenced the study outcomes? A-Dosage Dependency: The study revealed that the high dose of lutein (5mg/kg) had more significant effects on passive avoidance memory, spatial learning and memory, electrophysiological measures, hippocampal cell loss, and oxidative stress compared to the low dose (0.5mg/kg). However, the optimal dosage range and potential side effects of lutein were not thoroughly explored. Future studies should investigate a wider range of doses to determine the dose-response relationship and potential dose-dependent effects. B-Generalization to Human Population: The experiment was conducted on 2-vessel occlusion (2VO) rats, and the findings may not directly translate to humans. Animal models have inherent differences from human physiology, and caution should be exercised when extrapolating these results to clinical applications. Further research, including human clinical trials, is needed to validate the relevance of these findings in humans. C-Short-term Follow-up: The experiment assessed the effects of lutein treatment over a relatively short-term period. Long-term effects and potential sustained benefits or side effects of lutein administration were not investigated. Future studies should consider longer follow-up durations to better understand the persistence and durability of the observed effects 5. Based on the findings of this study, what are the potential implications for future research or clinical applications related to lutein administration in vascular dementia (VD) patients? Thank you for this good comment, we are in the process of designing and planning a clinical trial to investigate the effect of lutein on individuals suffering from vascular dementia: Given that the study was conducted on 2-vessel occlusion (2VO) rats, the translation of these findings to human patients with vascular dementia warrants further investigation. Conducting well-designed clinical trials involving individuals with vascular dementia will be essential to assess the efficacy and safety of lutein in a clinical setting. Long-term Effects and Safety Profile: The study primarily focused on short-term effects, and the long-term effects of lutein administration were not thoroughly explored. Future research should investigate the sustained benefits, potential side effects, and safety profile of lutein over extended treatment periods. Comparison with Existing Treatments: Comparative studies assessing the efficacy of lutein in comparison to existing treatments for vascular dementia could provide valuable insights. Understanding how lutein compares to standard treatments or other potential interventions will contribute to its potential integration into clinical practice. 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. Thank you, yes! Attachments Attachment Submitted filename: Responses to Reviewers.docx https://doi.org/10.1371/journal.pone.0302850.r002
12 Apr 2024 Decision Letter - Vara Prasad Saka, Editor The low and high doses administration of lutein improves memory and synaptic plasticity impairment through different mechanisms in a rat model of vascular dementia PONE-D-24-00251R1 Dear Dr. Haghani, 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Vara Prasad Saka Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0302850.r003
Formally Accepted
1 May 2024 Acceptance Letter - Vara Prasad Saka, Editor PONE-D-24-00251R1 PLOS ONE Dear Dr. Haghani, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Vara Prasad Saka Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0302850.r004

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