Synaptic Plasticity Dysfunctions in the Pathophysiology of 22q11 Deletion Syndrome: Is There a Role for Astrocytes?

Round 1

Reviewer 1 Report

This is a balanced, well-structured review providing mechanistic insights into 22q11 deletion syndrome with a focus on synaptic plasticity mechanisms, mitochondria and the role of glia. The review also discusses challenges related to the therapeutic development for this complex genetic disorder. I can recommend it for publication in its present form.

Author Response

We thank the reviewer for the positive comments and for allowing publication of this review on its present form.

Reviewer 2 Report

An excellent, well organized, and well written paper. I suggest, as minor changes, to describe the literature search strategy and to discuss briefly the strengths and limitations of the present review

Author Response

Dear editor,

 

Please find enclosed the revised version of our manuscript “Synaptic plasticity dysfunctions in the pathophysiology of 22q11 deletion syndrome: is there a role for astrocytes” which was submitted to your journal last March. We have raised all the issues that were pointed out by the reviewer 2. All revisions have been performed in strict accordance with his suggestions. Consequently, please find below a point-by-point report of all the changes we made with the appropriate page / line number. To facilitate your work, all changes have been marked up with the “Track Changes” function of MS Word in the revised manuscript. We hope these revisions will satisfy the reviewer’s requests.

 

Thank you very much.

 

With kind regard

 

Paola Bezzi.

 

Reviewer 2: An excellent, well organized, and well written paper. I suggest, as minor changes, to describe the literature search strategy and to discuss briefly the strengths and limitations of the present review.

Thanks to the reviewer for his/her comments and suggested improvements. Indeed, as the reviewer first pointed out, we did not mention any details on the literature search strategy we used to build the review. Actually, our strategy was primarily guided by the topic of the special issue to which we were invited, entitled “Molecular Mechanisms of Synaptic Plasticity (3.0): Genetic and Environmental Factors Involved in Neuronal Changes”. In the manuscript, we have then rectified by adding, p12-line 537-543, a specific section at the end of the manuscript providing details on the way articles have been selected and the specific terms that were correspondingly searched in PubMed. In this section, we also specify the care taken to provide both historical and most up-to-date references to respectively address well-known assertions and more recent and innovative data.

The reviewer also suggested to briefly discuss the strengths and limitations of our review. In accordance with this request, we have added a specific section p12 line 521-533 addressing these points. In this section, we first summarize the main message of our work, namely that anomalies in mitochondrial homeostasis inherent to the deletion of specific genes could be responsible for abnormal maturation of astrocytes during brain development and subsequently contribute to disturb synaptic plasticity, ultimately leading to cognitive dysfunctions that are core symptoms in the 22q11DS. Finally, we briefly discuss the pros and cons of our work.

Additionally, we have added extra text throughout the manuscript (p3-line 105-112, p7-line 274-277 and p8-lines 335-336 and 343-345) that we hope will not only help the reader keep the main message of the review in mind, but also the way we delineated our search strategy.

Author Response File: Author Response.docx