Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a well written and thorough review article on sleep as related to glial function and the endocannabinoid system. Topics covered include: the neurobiology of sleep, circadian sleep regulation, neural dynamics of sleep-wake transitions, sleep in the context of inflammation and stress, glial cells, the orchestrators of neural symphony including glial involvement in synaptic plasticity, glial involvement in the removal of waste products and brain homeostasis, glial role in sleep, dysfunction of the glial system and sleep disorders, insomnia, sleep-related breathing disorders, parasomnias, circadian rhythm disorders, restless leg syndrome, the endocannabinoid system with relevance to the sleep wake cycle and modulation of immune function and inflammation, ECS-glial axis, endocannabinoid regulation of CNS fluid dynamics, glial regulation of endocannabinoid function, synaptic plasticity and the endocannabinoid system in memory consolidation, and related therapeutic implications. Engaging graphics are included. This paper increases the reader’s understanding of the connection between sleep and the immune system while highlighting the role of specific cell types. The paper concludes with future directions and implications for targeting cannabinoid receptors to treat sleep disorders.

 

I can’t think of anything that should be added. The article is well written and thorough. I endorse for publication.

Author Response

I hope this message finds you well. We wanted to express our sincere gratitude for your thoughtful and positive review of our article on the intricate relationship between sleep, glial function, and the endocannabinoid system.

We appreciate the time and effort you invested in reviewing this paper. It is truly encouraging to receive your endorsement for publication, and your acknowledgment of the comprehensiveness of the article is deeply gratifying.

We are thrilled that the content resonated with your expectations, and we are especially pleased that you found the inclusion of engaging graphics to be effective in conveying the complexities of the subject matter.

Your encouragement motivates us to continue our endeavors in advancing scientific understanding, and we are grateful for your contribution to the refinement of our work.

Best Regards,

Reviewer 2 Report

Comments and Suggestions for Authors

In the review entitled “Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders” the author provides an extensive and organized description of the literature data concerning the interplay between glial cells, cannabinoid systems, sleep and inflammation.

It is extremely interesting to observe how the above players show a strong correlation with each other.

The authors provide important insights into the possible study of the complex network created by these key players, aimed at discovering new possible strategies/therapies to fight sleep disorders and neuroinflammation, with a possible positive effect on cognitive disorders.

The references reported are summarily poor but appropriate and include recent literature data, in line with the present study.

However, some points should be revised to better illustrate the present work.

-          In some sections of this manuscript (i.e. Introduction and Therapeutic Implication and Future Directions) no literature references have been included. These sections need to be revised by inserting appropriate citations.

-          Many sections of the manuscript had extensive areas (e.g., Glial Cells: the Orchestrators of the Neural Symphony) with an insufficient number of references. In addition, in many parts of this paper, the authors did not specify in detail to which reference the discussed topic belongs (e.g., Neural Dynamics of Sleep-Wake Transitions section). The authors should place citations more precisely within the text and expand the number of references used.

-           Whenever literature data is reported, the bibliographic references should be included at the end of the sentence. This is not done in many places in the manuscript (e.g. Conclusion section). 

-          Figure 1 and Figure 2. Some action mechanisms reported are not accurately explained (e.g. Figure 1. vesicular release) and the structures drawn are not sufficiently described (e.g. Figure 2.- Blood-brain barrier). In general, figures appear poor and not very communicative. Again, it would be necessary to be more precise and descriptive.

In summary, although the manuscript was finely edited, references seem to be few and sometimes inaccurately reported. The soundness of a scientific article/review is based on the citations included. The authors should therefore review this part of the manuscript.

Author Response

We want to extend our sincere gratitude for your insightful review of our manuscript.

Your constructive feedback has been invaluable in improving the quality and clarity of our work. I am pleased to inform you that we have carefully considered and addressed each of the concerns you raised during the review process.

Specifically, we have revised the manuscript to include appropriate citations in the Introduction and Therapeutic Implication and Future Directions sections. We have also expanded the number of references in areas where the manuscript had insufficient citations, ensuring a more comprehensive and well-supported presentation.

Regarding the placement of citations within the text, we have made adjustments to specify in detail to which reference each discussed topic belongs. Additionally, we have re-evaluated and improved the accuracy of the explanations for action mechanisms in Figure 1 and the descriptions of structures in Figure 2. The figures have been enhanced to be more precise and communicative.

We understand the importance of a robust reference base in a scientific article and have taken diligent steps to strengthen this aspect of our manuscript.

We appreciate your dedication to maintaining the highest standards in scientific literature, and we are confident that the revisions will address the concerns raised.

Thank you once again for your valuable feedback and contribution to the enhancement of our work.