The Devastating Effects of Sleep Deprivation on Memory: Lessons from Rodent Models

Round 1

Reviewer 1 Report

Review:  Advances in the Mechanism of Memory Impairment Due to Sleep Deprivation 

 

A brief summary.

 

In this article the authors summarize the effect of sleep deprivation (SD) on the memory process. The authors clearly identify the existing gap of understanding how SD ultimately could impair memory formation. They covered ample amounts of literature related with the effect of SD at the molecular level and its correlation with some alteration during the memory process. 

 

General concept comments 

 

This article enlisted a series of studies that evaluated the effect of SD at different mechanisms of the cellular level, and memory formation but failed to provide a comprehensive overview of the relationship between those processes. To better understand the value of this manuscript it may be beneficial to restrict and clarify some of the concepts used here. For example, in the context of memory formation it is recommended to identify which aspect of the memory process is affected (e.g. encoding, consolidation or retrieval). In the context of sleep, it may be helpful to clarify the duration of the SD in order to understand when lack of sleep potentially impairs memory. The title suggests that this review will provide some mechanisms of memory impairment produced by SD, however it only mentions that SD interferes with some of the processes at the cellular level and during memory formation. The authors should consider integrating the effect of SD at the circuit level in order to understand the relevance of the mechanism affected at the cellular level. The manuscript mentions some brain areas that participate in the memory formation, perhaps explaining why those areas are important during sleep and formation of memory could help to that aim. 

 

Specific comments 

 

line 34. It should say six hours (h) instead six h.

 

line 38. Specify what memory functions are maintained during sleep.

 

line 39. Please provides references for this sentence.

 

Line 51. There is a lack of explanation in Fig 1. Please describe with more details.

 

Lines 57. It would be beneficial to elaborate a bit more on the concept of “damaged by SD”.

 

Line 66. I suppose that REM here corresponds to Rapid eye movement sleep. 

 

Lines 126-128. There is a lack of explanation to understand those studies. Does not make sense REM SD inhibits LTP in vitro. I suggest rephrasing this sentence.

 

Line 131. It should be REM SD instead of RENSD.

 

Lines 263 and 284. There is the same subtitle. 

 

Line 299. Please provide the literature that supports that “sleep-wake cycle is regulated by 5-HT”.  

 

Author Response

Dear Reviewer,

Thank you for taking the time to review my article and provide valuable feedback. I have carefully considered your suggestions for improvement and have already made revisions.

Firstly, I have clarified the purpose and scope of the article and have defined and limited relevant concepts more rigorously. The relevant content has been added to the introduction section of the article. Secondly, I have specified the duration of sleep deprivation and integrated the effects of sleep deprivation at the circuit level to better understand the mechanisms affected at the cellular level (such as microglia and glial cells). Thirdly, I have elaborated further on the effects of sleep deprivation on memory in the article, including more details about the relationship between the duration of sleep deprivation and memory performance. These details are summarized in Table 1. Fourthly, I have provided a clearer description in the article of the effects of sleep deprivation on different stages of the memory process, including encoding, consolidation, and retrieval. Finally, I have strengthened the description of the brain regions involved in memory formation and explained why these areas are so important during sleep and the memory consolidation process. Please refer to chapter 2 of the article for details.

Overall, I hope that these revisions will make the review paper more useful to researchers and healthcare professionals interested in understanding the impact of sleep deprivation

Please see the details in attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

I have gone through your manuscript and I found it to be informative and well-researched. Your thorough examination of the various pathways through which sleep deprivation affects memory function, including synaptic plasticity, neuroinflammation, oxidative stress, genes, and neurotransmitters, is commendable. I appreciate the emphasis on the need for further research in other brain regions to comprehensively and systematically investigate the mechanisms underlying the effect of sleep deprivation on memory. Overall, your review is an important contribution to the field and provides valuable insights for future studies.

Author Response

Dear Reviewer 2,

Thank you very much for taking the time to review my manuscript and for your thoughtful and positive feedback. I am pleased to hear that you found my article informative and well-researched. Your suggestion of the need for further research in other brain regions to comprehensively and systematically investigate the mechanisms underlying the effect of sleep deprivation on memory is well-received and I agree that it is an important area for future study.

I fully concur with your assertion that further research is necessary to thoroughly examine the mechanisms by which sleep deprivation impacts memory, specifically in other brain regions. To enhance the comprehensiveness of the article, I have included additional literature discussing the significance of various brain regions for memory function and the adverse effects of sleep disorders on these regions. Refer to the following:

“The hippocampus is responsible for the processing, consolidation, and retrieval of short- and long-term memory and for spatial navigation and orientation[1,2]. Proteins that are linked to the hippocampus are crucially involved in memory formation[3]. SD could induce damages to hippocampal neurons and reduce the size and volume of the hippocampus, impairing hippocampal-dependent memory functions and resulting in difficulties in recalling past events and forming new memories[4]. SD can affect hippocampal function at the molecular level by decreasing encoding-related activity within the hippocampus[5]. The thalamus is involved in regulating sleep-wake cycles during SD and emotional processing[6]. Similarly, SD can lead to decreased activity in the thalamus, resulting in impaired sensory perception and processing[7]. The encoding of working memory relies on the prefrontal cortex, which plays a crucial role in attention and memory[8,9]. Reduced prefrontal cortex activity caused by SD can impair cognitive function, including attention, working memory, and fear memory consolidation[10,11]. The anterior cingulate cortex modulates the frontoparietal functional connectivity between resting-state and working memory tasks[12] Additionally, SD can cause decreased anterior cingulate cortex activity, leading to impaired emotional regulation and decision-making abilities[13,14].”

The sources cited in the literature [6,19-31] are as follows,

6. Crowley, R.; Bendor, D.; Javadi, A.H. A review of neurobiological factors underlying the selective enhancement of memory at encoding, consolidation, and retrieval. Prog Neurobiol 2019, 179, 101615, doi:10.1016/j.pneurobio.2019.04.004.
7. Xu, M.; Liu, X.; Wang, Q.; Zhu, Y.; Jia, C. Phosphoproteomic analysis reveals the effects of sleep deprivation on the hippocampus in mice. Mol Omics 2022, 18, 677-685, doi:10.1039/d2mo00061j.
8. Aijuan, T.; Anding, D.; Mengmeng, Z.; Shiming, L.; Guili, Y. The role of c-fos gene in the enhancement of memory in the hippocampus of mouse. Journal of Yangzhou University 2022, 43, 67-72, doi:10.16872/j.cnki.1671-4652.2022.03.011.
9. Zhou, H.; Wu, J.; Gong, Y.; Zhou, Z.; Wang, J. Isoquercetin alleviates sleep deprivation dependent hippocampal neurons damage by suppressing NLRP3-induced pyroptosis. Immunopharmacol Immunotoxicol 2022, 44, 766-772, doi:10.1080/08923973.2022.2082976.
10. Krause, A.J.; Simon, E.B.; Mander, B.A.; Greer, S.M.; Saletin, J.M.; Goldstein-Piekarski, A.N.; Walker, M.P. The sleep-deprived human brain. Nat Rev Neurosci 2017, 18, 404-418, doi:10.1038/nrn.2017.55.
11. Li, B.Z.; Cao, Y.; Zhang, Y.; Chen, Y.; Gao, Y.H.; Peng, J.X.; Shao, Y.C.; Zhang, X. Relation of Decreased Functional Connectivity Between Left Thalamus and Left Inferior Frontal Gyrus to Emotion Changes Following Acute Sleep Deprivation. Front Neurol 2021, 12, 642411, doi:10.3389/fneur.2021.642411.
12. Chen, Y.; Pan, L.; Ma, N. Altered effective connectivity of thalamus with vigilance impairments after sleep deprivation. J Sleep Res 2022, 31, e13693, doi:10.1111/jsr.13693.
13. Bahmani, Z.; Clark, K.; Merrikhi, Y.; Mueller, A.; Pettine, W.; Isabel Vanegas, M.; Moore, T.; Noudoost, B. Prefrontal Contributions to Attention and Working Memory. Curr Top Behav Neurosci 2019, 41, 129-153, doi:10.1007/7854_2018_74.
14. Dixsaut, L.; Gräff, J. The Medial Prefrontal Cortex and Fear Memory: Dynamics, Connectivity, and Engrams. Int J Mol Sci 2021, 22, doi:10.3390/ijms222212113.
15. Feng, P.; Becker, B.; Zheng, Y.; Feng, T. Sleep deprivation affects fear memory consolidation: bi-stable amygdala connectivity with insula and ventromedial prefrontal cortex. Soc Cogn Affect Neurosci 2018, 13, 145-155, doi:10.1093/scan/nsx148.
16. Chauveau, F.; Laudereau, K.; Libourel, P.A.; Gervasoni, D.; Thomasson, J.; Poly, B.; Pierard, C.; Beracochea, D. Ciproxifan improves working memory through increased prefrontal cortex neural activity in sleep-restricted mice. Neuropharmacology 2014, 85, 349-356, doi:10.1016/j.neuropharm.2014.04.017.
17. Di, X.; Zhang, H.; Biswal, B.B. Anterior cingulate cortex differently modulates frontoparietal functional connectivity between resting-state and working memory tasks. Hum Brain Mapp 2020, 41, 1797-1805, doi:10.1002/hbm.24912.
18. Zhang, L.; Shao, Y.; Jin, X.; Cai, X.; Du, F. Decreased effective connectivity between insula and anterior cingulate cortex during a working memory task after prolonged sleep deprivation. Behav Brain Res 2021, 409, 113263, doi:10.1016/j.bbr.2021.113263.
19. Noorafshan, A.; Karimi, F.; Karbalay-Doust, S.; Kamali, A.M. Using curcumin to prevent structural and behavioral changes of medial prefrontal cortex induced by sleep deprivation in rats. Excli j 2017, 16, 510-520, doi:10.17179/excli2017-139.

I greatly value your feedback and will take it into consideration as I continue to develop my research. Thank you again for your time and expertise in reviewing my paper. We thank professional editors and reviewers for your warm work, and hope that the corrections will be approved. We look forward to your consideration.

 

Sincerely,

Pinqiu Chen, WeiKang Ban, WenYan Wang, Yuyang You, Zhihong Yang

Apr. 14, 2023

Reviewer 3 Report

Manuscript Number: clockssleep-2283206

Title: Advances in the Mechanism of Memory Impairment Due to Sleep Deprivation

 

This review paper aimed at examining the effects of sleep deprivation mainly on memory function and on learning function, as well, in terms of synaptic plasticity, neuroinflammation, oxidative stress, genes, and neurotransmitters.

Overall, the paper is well-written and able to create the interest of the reader.

The authors appear well-informed on the extant literature.

Prior to publication, though, I believe minor revisions should be made to strengthen the manuscript. Below, I will give some suggestions for revising the paper, which I believe would be beneficial.

1. Your literature review is nicely written. However, the reasons you have selected to include in your review paper the 21 research papers, that are presented in Table 1, are not clear. Please, clarify further which were the databases (PubMed, Scopus?) and the keywords that you used in your investigation. You could, also. use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), which is an evidence-based minimum set of items for reporting in systematic reviews.

2. page 2, lines 47-48: Please, add at least 2 references.

3. page 11, lines 457-459: Please, check references 29 & 30.

4. pages 11-12, lines 460-462: Please, check references 31 & 32.

Comments for author File: Comments.docx

Author Response

Dear Reviewer3,

Thank you very much for your feedback. I value the concerns you raised. Electronic searches were conducted in the PubMed, Google Scholar, Web of Science, and CNKI databases for recent publications, using the following search terms: Sleep Deprivation AND Sleep; Memory Function AND Sleep; Insomnia AND Memory Function; Sleep Deprivation and Memory Impairment; Sleep Deprivation AND Mechanisms of Injury. Initially, we focused on recent publications and subsequently reviewed the reference sections of relevant articles to identify older publications that aligned with our research goals. Finally, we selected the most recent articles that provided current and relevant information on our predefined subtopics.

We selected 21 representative articles that were highly relevant to the topic and summarized them to provide a comprehensive overview of existing literature on the specific topic. The aim of these studies is to elucidate the effects of diverse sleep deprivation paradigms, varying deprivation durations, and inter-species differences on multiple memory functions. we have further categorized and summarized the table.

Regarding your second question, I agree that PRISMA is a valuable tool for systematic reviews to ensure accuracy and transparency in literature reviews. However, it's important to note that our literature review is not a systematic review but a narrative review aimed at providing a comprehensive overview of existing literature on a specific topic. Nevertheless, I appreciate your suggestion and will consider it in any future reviews to ensure accuracy and transparency.

I hope this response better addresses your concerns. Please let me know if you have any other questions or concerns.

 

Point 2: page 2, lines 47-48: Please, add at least 2 references.

Response 2:

Based on your helpful suggestion, I have added 4 references at the appropriate positions, the specific original article is as follows:

“SD may improve memory, but others stated that SD increases the risk of various diseases and negatively affects learning and memory[14-17]”

14. Cho, J.W.; Duffy, J.F. Sleep, Sleep Disorders, and Sexual Dysfunction. World J Mens Health 2019, 37, 261-275, doi:10.5534/wjmh.180045.
15. Clark, A.J.; Salo, P.; Lange, T.; Jennum, P.; Virtanen, M.; Pentti, J.; Kivimäki, M.; Rod, N.H.; Vahtera, J. Onset of Impaired Sleep and Cardiovascular Disease Risk Factors: A Longitudinal Study. Sleep 2016, 39, 1709-1718, doi:10.5665/sleep.6098.
16. Sumowski, J.F.; Horng, S.; Brandstadter, R.; Krieger, S.; Leavitt, V.M.; Katz Sand, I.; Fabian, M.; Klineova, S.; Graney, R.; Riley, C.S.; et al. Sleep disturbance and memory dysfunction in early multiple sclerosis. Ann Clin Transl Neurol 2021, 8, 1172-1182, doi:10.1002/acn3.51262.
17. Zhu, B.; Dong, Y.; Xu, Z.; Gompf, H.S.; Ward, S.A.; Xue, Z.; Miao, C.; Zhang, Y.; Chamberlin, N.L.; Xie, Z. Sleep disturbance induces neuroinflammation and impairment of learning and memory. Neurobiol Dis 2012, 48, 348-355, doi:10.1016/j.nbd.2012.06.022.

Point 3: page 11, lines 457-459: Please, check references 29 & 30.

Response 3: These two references have already been checked and revised, as follows:

I have added some references in the article, and the order of the references has changed

53           Yan-yan, W.; Hong-sheng, B.; Hai-ni, L.; Yu-fei, C.; Wen-wen, L.; Ting-li, L.; Li-li, H. Effects of L-tetrahydropalmatine on learning and memory，and sleep rhythm in rats with rapid eye movement sleep deprivation. Chinese Traditional Patent Medicine 2022, 44, 2812-2817.

54. Qianwei, Y.; Xingping, Z.; Deqi, Y.; Kaikai, W.; Zhenpeng, T.; Ning, D. Expression differences of orexin receptors in related organs of insomnia rats with lung storing no inferior spirit. Shanghai Journal of Traditional Chinese Medicine 2022, 56, 75-80, doi:10.16305/j.1007-1334.2022.2108104.

 

Point 4: pages 11-12, lines 460-462: Please, check references 31 & 32.

Response 4: These two references have already been checked and revised, as follows:

I have added some references in the article, and the order of the references has changed

55. Hu, Y.; Yin, J.; Yang, G. Melatonin upregulates BMAL1 to attenuate chronic sleep deprivation-related cognitive impairment by alleviating oxidative stress. Brain Behav 2023, 13, e2836, doi:10.1002/brb3.2836.
56. Xiong, X.; Zuo, Y.; Cheng, L.; Yin, Z.; Hu, T.; Guo, M.; Han, Z.; Ge, X.; Li, W.; Wang, Y.; et al. Modafinil Reduces Neuronal Pyroptosis and Cognitive Decline After Sleep Deprivation. Front Neurosci 2022, 16, 816752, doi:10.3389/fnins.2022.816752.

 

We thank professional editors and reviewers for your warm work, and hope that the corrections will be approved. We look forward to your consideration.

 

Sincerely,

Pinqiu Chen, WeiKang Ban, WenYan Wang, Yuyang You, Zhihong Yang

Apr. 14, 2023

-----End of Reply to Reviewer #3------

Round 2

Reviewer 1 Report

Dear authors, 

I am glad to received the current version of this manuscript. I noticed that there was a genuine effort to integrated my previous comments. Overall, I think this review synthesize well the effect of the SD in memory.

all the best 

Author Response

Thank you for taking the time to review our manuscript and for your valuable feedback. We are pleased to hear that our efforts to integrate your previous comments have been successful.

We appreciate your positive comments regarding the synthesis of the effect of the SD in memory. It is our goal to provide a comprehensive and accurate understanding of the topic, and we are glad that our efforts have been recognized.

Once again, we thank you for your constructive comments, and we will carefully consider all of your suggestions as we work towards improving the manuscript.

Sincerely,

Pinqiu Chen, WeiKang Ban, WenYan Wang, Yuyang You, Zhihong Yang

May. 02, 2023