Chronic Unpredictable Stress Alters Brain Tryptophan Metabolism and Impairs Working Memory in Mice without Causing Depression-Like Behaviour

Review Data

Q: Is the topic relevant to the journal area of interest? Is it contemporary and interesting for

researchers?

A: Good

Abstract & Keywords

Q: Are all required components included in the abstract? Are the keywords appropriately chosen?

A: Very good

Goal

Q: Is the goal explicitly stated in the Introduction? Is its formulation clear and unambiguous?

A: Excellent

Structure

Q: Is the paper's structure coherent? Is it in coherence with the goal of the paper?

A: Very good

Tools and Methods

Q: Are methods the author uses adequate and well used?

A: Very good

Discussion & Conclusion

Q: Is it related to the results presented before? Do you consider them as coherent?

A: Excellent

Comments: The Discussion section, by measuring central and peripheral kynurenine pathway metabolites and depressive-like behavioural changes, establishes that dysregulated tryptophan metabolism pathways are a possible mechanistic link between chronic stress and depressive-like phenotypes. It thoroughly analyses the observations presented in this study which helps to determine the role of downstream tryptophan metabolism pathways in depressive-like behavioural effects induced by chronic unpredictable stress (CUS). Relevant literature has been cited to support the Discussion. Lastly, it concludes that alterations in the kynurenine pathway of tryptophan metabolism is involved in the pathogenesis of inflammation-induced depression.

Literature

Q: Does the author utilize relevant literature?

A: Very good

Author's knowledge

Q: What is the level of the author’s knowledge? Does the author utilize all recent contributions relevant to the topic?

A: Very good

Length

Q: Is the length of the paper adequate to the significance of the topic? Do you suggest shortening the paper without losing its value?

A: Good

Figures & Tables

Q: Does the author use them suitably? Are legend and notations clear?

A: Very good

Comments: Figure 1G has neither been marked in the provided figure nor it has been mentioned in the text section of the manuscript and Figure 1B has not been marked in the figure.

Writing style

Q: Is it clear and understandable?

A: Good

Comments:

·       In the sentence under the 10^th point Reverse Light Cycle under the subheading Chronic Unpredictable Stress Paradigm of Methods, “##” were given before “watt bulbs”. These should be checked by the author.

·       In the 1^st sentence of the Acknowledgement, “from the” has been repeated twice. Hence, duplicate one should be removed from the sentence.

·       Words like “kynurenic”, “hydroxyanthranilic”, “hydroxykynurenine” are misspelled in the text section of the article.

·       Articles are missing in several places throughout the text.

Further comments on the paper

Comments: This study focuses on temporal central and peripheral changes in tryptophan metabolism and concomitant depressive-like behavioural phenotype induced during the progression of chronic unpredictable stress (CUS) by studying 8-10-week-old male C57BL/6J mice. The purpose of this study is to observe the behavioural effects and to determine depressive-like phenotypes induced by CUS. The findings reveal that an elevation occurred in the concentrations of central tryptophan, kynurenine, picolinic acid (PA), and 5-hydroxyindoleacetic acid (5-HIAA) whereas central serotonin, xanthurenic acid (XT), and kynurenic acid (KYNA) levels were markedly decreased. Although, no anhedonia-like behaviour or anxiety-like behaviour was observed. This study further discovers that CUS impairs hippocampal-dependent working memory and enhances nascent nesting behaviour which are associated with increased brain kynurenine pathway metabolism leading to accumulation of picolinic acid and a significant reduction in serotonin levels.

Q: Would you recommend this manuscript for further publication?

A: Yes - Suitable to be published

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Science Repository Team