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Identification of serum N-glycoproteins as a biological correlate underlying chronic stress response in mice

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Abstract

Glycosylation is a post-translational protein modification in eukaryotes and plays an important role in controlling several diseases. N-glycan structure is emerging as a new paradigm for biomarker discovery of neuropsychiatric disorders. However, the relationship between N-glycosylation pattern and depression is not well elucidated to date. This study aimed to explore whether serum N-glycan structures are altered in depressive-like behavior using a stress based mouse model. We used two groups of BALB/c mice; (i) treated group exposed to chronic unpredictable mild stress (CUMS) as a model of depression, and (ii) control group. Behavioral tests in mice (e.g., sucrose preference test, forced swimming test, and fear conditioning test) were used to evaluate the threshold level to which mice displayed a depressive-like phenotype. Serum N-glycans were analyzed carefully using glycoblotting followed by Matrix-assisted laser desorption ionization-time of flight/mass spectrometry (MALDI-TOF/MS) to exhibit N-glycan expression levels and to illustrate the changes in the N-glycome profile. N-glycan expression levels were commonly altered in the depressive-like model and correlated well with the behavioral data. Our results indicated that sialylated N-glycan was identified as a biomarker associated with depressive symptoms, which may have utility as a candidate biomarker for the clinical diagnosis and monitoring of depression.

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Acknowledgements

The authors would like to express sincere thanks to the Drug Discovery Research Group at Nishimura Laboratory, Faculty of Advanced Life Sciences, Hokkaido University, Japan, for learning the glycomics technique. Thanks to Sohag University to fund the project, proposal ID: #271, appreciations to Dr. Michael G. Wolfe at Biointerfaces Institute, McMaster University, Hamilton, Ontario, Canada for the language edition and Prof. Mahmoud Salah El-Tarabany, head of Animal Wealth Development, Faculty of Veterinary Medicine, Zagazig University, Egypt for the statistical revision.

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Contributions

MEM and IFR designed the survey protocol, conceived the study, supervised data collection procedures, and drafted the final version of the manuscript; KhEl-DA, AA, SM, EKHA and AFA-E wrote the statistical analysis, analysed the data and shared in experimental protocol; MY, HMD, DS, AE, HHM, AEl-LH, RMI, OS and AG have finalized the experimental design and revised the manuscript. All authors contributed to, edited, and approved the final manuscript as submitted.

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Correspondence to Motamed Elsayed Mahmoud, Ibrahim F. Rehan or Abd El-Latif Hesham.

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The authors declare that they have no conflict of interests.

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The protocol was approved by the Ethics Committee for Animal Experimentation at Sohag University, Faculty of Medicine, Faculty Council No (282), Decree (7463), 14th September 2017.

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Mahmoud, M.E., Rehan, I.F., El-Dawy Ahmed, K. et al. Identification of serum N-glycoproteins as a biological correlate underlying chronic stress response in mice. Mol Biol Rep 46, 2733–2748 (2019). https://doi.org/10.1007/s11033-019-04717-7

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