PONE-D-23-35885Class I Histone Deacetylases inhibition reverses memory impairment induced by acute stress in micePLOS ONE

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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: Partly

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

Reviewer #1: No

Reviewer #2: Yes

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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: No

Reviewer #2: Yes

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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

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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 paper entitled „Class I Histone Deacetylases inhibition reverses memory impairment induced by acute stress in mice” by Martínez-Pacheco et al. demonstrated the possible link between acute stress, memory disturbances and downregulation of HDAC. The topic is quite important due to the complexicity and still not fully understand relationship between the stress and learning and memory processes. The manuscript is well-written but there are some deficiences, which needs to be addressed before the acceptance. All comments are indicated below.

In the Introduction there should be some explanation about the rationale to use HDACs inhibitors in the study (PB and IN14), based on available literature.

In case of animals Author should write the total amount of used animals. Moreover there should be some information about the enrichment used and handling. Authors mentioned about handling only in case of object recognition test, what about the other tests?

Why the spontaneous motor activity was measured for 5 min? Please explain.

„Novel object recognition test” should be actually the „object recognition test”

There are some shortcuts, which are not explained in the text: LTM (line 114), STM (line 126)

Line 167-168 – please explain how this confirmation of animals equall preferences was performed?

Line 183 – Authors write „rats” whereas only mice were included in the Materials and Methods section

„post hoc” should be written in italic

Line 235-236 – please explain why the HDAC2 activity was evaluated onlu in animals from ETM test?

Line 269 p=0.0617 is not significant – please correct the sentence.

Please explain why the number of animals used in case of plasma corticosterone level was only 4 per group?

Line 288-289 – in the Fig.4 in „vertical” – this increase doesn’t indicate to be significant.

Line 320 „mg/kg” with lowercase

Line 339 Authors write Fig.6D, which I didn’t find in the manuscript

In the „Discussion” section there should be more references to performed tests, like short explanation what can be measured in the specific test (please see line 139-141 – these information should be rather in the Discussion, no in the Method section)

Authors should include also the limitations of performed study.

Figure 1 should also include the spontaneous locomotor activity test.

Figure 5C In case of PB-S after 1h – shouldn’t be there any significance vs. VEH-S?

Figure 6B and 7A These charts are poorly legible, please try to correct them.

Figure 7B In case of PB-S– shouldn’t be there any significance vs. VEH-S?

Figure 8B What about the significance between VEH-S and PB-S/IN14-S?

Reviewer #2: The manuscript by Martinez-Pacheco and colleagues studies the effects of acute stress on memory in mice and investigates the role of histone deacetylase 2 (HDAC2) via systemic treatment with HDAC inhibitors. Acute stress was induced by forced swimming, and the increased stress level was confirmed by plasma corticosterone level. Afterwards, three behavioral tests were conducted in independent groups and a negative effect of acute stress on short-term and long-term memory was revealed. Such memory impairment was reversed by HDAC2 inhibitors PB and IN14. In the end, the authors compared the HDAC2 levels in different treatments and found that the memory impairment is paralleled with increased HDAC2 levels. Together, this study claimed that the acute stress induces memory impairment via increased HDAC2 expression, and the memory dysfunction could be reversed by HDAC2 inhibition. The experiments are well designed and can well support their conclusions

Class I Histone Deacetylases inhibition reverses memory impairment induced by acute stress in mice

PONE-D-23-35885R1

Dear Dr. Quirarte,

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,

Peng Zhong, Ph.D.

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. 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: (No Response)

Reviewer #2: Yes

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

Reviewer #1: (No Response)

Reviewer #2: Yes

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4. 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: (No Response)

Reviewer #2: Yes

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5. 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: (No Response)

Reviewer #2: Yes

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6. 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: (No Response)

Reviewer #2: The authors have addressed my concerns in the revised manuscript. This version now is suitable to be published.

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Reviewer #1: No

Reviewer #2: No

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