Low p-SYN1 (Ser-553) Expression Leads to Abnormal Neurotransmitter Release of GABA Induced by Up-Regulated Cdk5 after Microwave Exposure: Insights on Protection and Treatment of Microwave-Induced Cognitive Dysfunction
Round 1
Reviewer 1 Report
The abstract needs some rewording in terms of motivation. The effect of microwave on the cells is not mentioned at all while that is the first line in the Introduction.
The introduction of microwave induced functional deficits need more elaboration and references needed for statement on line 37.
Line 43 the word word contingented needs to be replaced by contingent
Mention either in materials and methods section or in Results section the different number of animals in the different groups. It is not clear how many were in the exposed, sham and how many rats underwent Morris Water Maze.
Line 70 - times should be in 24 hr or 12 hr format not both.
Line 71 - rephrase sentence
Line 73 - the first line seems a repeat of the title
Move the “Cell Culture” subsection to before the Microwave Exposure Dosimetry
Line 86, missing a “which” or rephrase sentence
Line 100 - what is SAR ? Expand and explain
Line 104 - needs to rephrased
Line 122 - first line reads like a title and the second sentence needs rephrasing
Line 187 - needs reference
Line 213 - what was the previous observation ? Increase , decrease or no change ?
Line 216 - Is this referring to Fig 3 ?
Discussion
Microwave technology has been in place for many years. What is unclear is which specific application of the microwave technology are the authors trying to address ?
The authors should also address the minimum strength of microwave power that leads to cognitive impact and discuss the effects with increase wattage of the microwave ?
Author Response
The abstract needs some rewording in terms of motivation. The effect of microwave on the cells is not mentioned at all while that is the first line in the Introduction.
Answer: The motivation and the effect of microwave on cells had been added in the abstrac.
The introduction of microwave induced functional deficits need more elaboration and references needed for statement on line 37.
Answer: Thank you for your suggestions. Changes have been made according to your instructions.
Line 43 the word word contingented needs to be replaced by contingent
Answer: This error has been corrected.
Mention either in materials and methods section or in Results section the different number of animals in the different groups. It is not clear how many were in the exposed, sham and how many rats underwent Morris Water Maze.
Answer: The numbers of rats in different groups has been added in the materials and methods section.
Line 70 - times should be in 24 hr or 12 hr format not both.
Answer: Thank you for your suggestions. We have modified the format of the time to be consistent.
Line 71 - rephrase sentence
Answer: This sentence has been rephrased.
Line 73 - the first line seems a repeat of the title
Answer: This repeat has been corrected.
Move the “Cell Culture” subsection to before the Microwave Exposure Dosimetry
Answer: This part has been moved on the top of Microwave Exposure Dosimetry according to your suggestions. Thank you.
Line 86, missing a “which” or rephrase sentence
Answer: Thank you for your suggestion. This sentence has been revised.
Line 100 - what is SAR? Expand and explain
Answer: SAR is the abbreviation of Specific Absorb Rate .We have added it in the manuscript.
Line 104 - needs to rephrased
Answer: We have rephrased this sentence in the revised manuscript.
Line 122 - first line reads like a title and the second sentence needs rephrasing
Answer: We have revised and rephrased this sentence.
Line 187 - needs reference
Answer: We have revised this sentence.
Line 213 - what was the previous observation? Increase, decrease or no change?
Answer: The previous observation has been elaborated.
Line 216 - Is this referring to Fig 3?
Answer: Yes, it is referring to Fig 3.
Discussion
Microwave technology has been in place for many years. What is unclear is which specific application of the microwave technology are the authors trying to address?
Answer: This study aimed to explain the mechanisms through which microwave exposure causes cognitive deficits. These parameters are applicable to some people who are accidentally exposed or have to be exposed to high-power microwave radiation, specific to the parameters used in this paper, its purpose is to reproduce the cognitive impairment caused by high-dose accidental microwave radiation.
The authors should also address the minimum strength of microwave power that leads to cognitive impact and discuss the effects with increase wattage of the microwave?
Answer: The minimum strength of microwave power that leads to cognitive impact was 10 mW/cm2, and the damage getting more serious with the increase of power density in a dose-dependent manner. (First paragraph in Discussion)
Author Response File: 
Author Response.pdf
Reviewer 2 Report
This is an overall nice article that aimed to explain the mechanisms through which microwave exposure causes cognitive deficits. However, extensive English editing is required.
Moreover, the abstract should be improved. The abstract constitutes the main source of information for most researchers. It has to be well reported and well written. For instance: ‘‘Abnormal neurotransmission is mediated by p-SYN1, which also results in cognitive dysfunction’’. This sentence conveys the message that p-SYN1 exerts a negative effect on neurotransmission, while the truth is that p-SYN1 exerts a regulatory effect on neurotransmission. Similar mistakes can be traced throughout the document. Please collaborate with a native English speaker to avoid such mistakes (both in the abstract and throughout the main text).
‘‘Since the phosphorylation of SYN1 is regulated by different kinases, in this study, the specific upstream mechanism regulating this effect was investigated.’’ Please make clear that your purpose was to investigate the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release.
Moreover, the abstract should contain information regarding your methods and materials (it is not clear if it is an animal or cell-based investigation, the number of subjects analysed is not reported, the means through which you reached your findings and conclusions are not clear).
With respect to the results section, please report number of analysed subjects (or units) in every step. Also, do not include previous findings (e.g., ‘‘In our earlier study, the expression of other phosphorylated forms of SYN1, such as p-SYN1 (ser-553), p-SYN1 (ser-62/67) and p-SYN1 (ser-603) were reported [16].’’) but rather leave them for the discussion section.
Again, although your article can enhance existing literature, important information might be ‘‘lost’’ due to deficient reporting or inappropriate writing. Please make sure that these issues will be taken care of.
Author Response
This is an overall nice article that aimed to explain the mechanisms through which microwave exposure causes cognitive deficits. However, extensive English editing is required.
Answer: We have provided the manuscript to AJE and requested an editor with the appropriate experience. Thank you very much for your suggestion.
Moreover, the abstract should be improved. The abstract constitutes the main source of information for most researchers. It has to be well reported and well written. For instance: ‘‘Abnormal neurotransmission is mediated by p-SYN1, which also results in cognitive dysfunction’’. This sentence conveys the message that p-SYN1 exerts a negative effect on neurotransmission, while the truth is that p-SYN1 exerts a regulatory effect on neurotransmission. Similar mistakes can be traced throughout the document. Please collaborate with a native English speaker to avoid such mistakes (both in the abstract and throughout the main text).
Answer: The abstract has been rewritten. The ambiguity in the text has been corrected.
“Since the phosphorylation of SYN1 is regulated by different kinases, in this study, the specific upstream mechanism regulating this effect was investigated.’’ Please make clear that your purpose was to investigate the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release.
Answer: Thank you very much for your wonderful suggestions. We have revised this sentence in accordance with your comments.
Moreover, the abstract should contain information regarding your methods and materials (it is not clear if it is an animal or cell-based investigation, the number of subjects analysed is not reported, the means through which you reached your findings and conclusions are not clear).
Answer: The abstract has been rewritten. The number of analysed subjects has been provided in Animals and Groups section.
With respect to the results section, please report number of analysed subjects (or units) in every step. Also, do not include previous findings (e.g., ‘‘In our earlier study, the expression of other phosphorylated forms of SYN1, such as p-SYN1 (ser-553), p-SYN1 (ser-62/67) and p-SYN1 (ser-603) were reported [16].’’) but rather leave them for the discussion section.
Answer: Thank you for your suggestion. The number of analysed subjects has been provided in Animals and Groups section. And the sentence about the results of previous study has been moved to discussion section.
Again, although your article can enhance existing literature, important information might be ‘‘lost’’ due to deficient reporting or inappropriate writing. Please make sure that these issues will be taken care of.
Answer: Thank you very much for your suggestion. We have carefully revised the full text, sent this article to AJE and asked the relevant expert for revision of English. These errors and deficiencies have been corrected.
Author Response File: Author Response.pdf
Reviewer 3 Report
Overall, I support publication of this paper but I do suggest some edits that may make the paper easier to read and comprehend for the average reader.
The authors should take care to be sure that all abbreviations are defined with the first use.
The introduction can be strengthened by providing more information on the significance of this research. I suggest moving the first paragraph of the discussion to the introduction. It might also be worth mentioning the number of people thought to experience the negative effects of microwave exposure (if known) to show the scope of the problem. It might also be worth mentioning that the use of microwaves may have military uses (i.e., Havana syndrome). Again, this could demonstrate the significance of this research.
In the methods or the discussion, it would be helpful to mention what the limit of microwave exposure for humans is in order to put into context the exposure levels given to the rats in this study.
In the discussion section, a graphic of the biological pathways impacted by microwave exposure would be helpful for the reader.
A better description of the known pharmacology of U0126 and roscovitine will be helpful to the reader.
Finally, several typos were observed. On line 45, us 'a' instead of 'an'. On line 73 use the term 'sacrificed' instead of 'killed'. On line 161, there should be a space between 'then' and 'the'. On line 162, 'stimulated' is misspelled.
Author Response
Overall, I support publication of this paper but I do suggest some edits that may make the paper easier to read and comprehend for the average reader.
Answer: Thank you very much for your approval and suggestions for this article.
The authors should take care to be sure that all abbreviations are defined with the first use.
Answer: We have marked all abbreviations with their full names when they first appear.
The introduction can be strengthened by providing more information on the significance of this research. I suggest moving the first paragraph of the discussion to the introduction. It might also be worth mentioning the number of people thought to experience the negative effects of microwave exposure (if known) to show the scope of the problem. It might also be worth mentioning that the use of microwaves may have military uses (i.e., Havana syndrome). Again, this could demonstrate the significance of this research.
Answer: The significance of this research has been strengthened in introduction. However, this study is aimed at the population accidentally exposed to high-power microwave radiation. Due to many reasons, the number is difficult to estimate. “Havana syndrome” was mentioned in the introduction to address the important of this study.
In the methods or the discussion, it would be helpful to mention what the limit of microwave exposure for humans is in order to put into context the exposure levels given to the rats in this study.
Answer: The limitations of microwave exposure has been added in the Microwave Exposure and Dosimetry section.
In the discussion section, a graphic of the biological pathways impacted by microwave exposure would be helpful for the reader.
Answer: The graphic of the biological pathways impacted by microwave exposure has been added as Fig.9.
A better description of the known pharmacology of U0126 and roscovitine will be helpful to the reader.
Answer: This description has been supplemented.
Finally, several typos were observed. On line 45, us 'a' instead of 'an'. On line 73 use the term 'sacrificed' instead of 'killed'. On line 161, there should be a space between 'then' and 'the'. On line 162, 'stimulated' is misspelled.
Answer: Thank you very much. These errors have been corrected.
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
Thank you for considering my recommendations.
