Proteomic association with age-dependent sex differences in Wisconsin Card Sorting Test performance in healthy Thai subjects

Abstract Sex differences in cognitive function exist, but they are not stable and undergo dynamic change during the lifespan. However, our understanding of how sex-related neural information transmission evolves with age is still in its infancy. This study utilized the Wisconsin Card Sorting Test (W...

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Main Authors: Chen Chen, Bupachad Khanthiyong, Benjamard Thaweetee-Sukjai, Sawanya Charoenlappanit, Sittiruk Roytrakul, Samur Thanoi, Gavin P. Reynolds, Sutisa Nudmamud-Thanoi
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-46750-4
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author Chen Chen
Bupachad Khanthiyong
Benjamard Thaweetee-Sukjai
Sawanya Charoenlappanit
Sittiruk Roytrakul
Samur Thanoi
Gavin P. Reynolds
Sutisa Nudmamud-Thanoi
author_facet Chen Chen
Bupachad Khanthiyong
Benjamard Thaweetee-Sukjai
Sawanya Charoenlappanit
Sittiruk Roytrakul
Samur Thanoi
Gavin P. Reynolds
Sutisa Nudmamud-Thanoi
author_sort Chen Chen
collection DOAJ
description Abstract Sex differences in cognitive function exist, but they are not stable and undergo dynamic change during the lifespan. However, our understanding of how sex-related neural information transmission evolves with age is still in its infancy. This study utilized the Wisconsin Card Sorting Test (WCST) and the label-free proteomics method with bioinformatic analysis to investigate the molecular mechanisms underlying age-related sex differences in cognitive performance in 199 healthy Thai subjects (aged 20–70 years), as well as explore the sex-dependent protein complexes for predicting cognitive aging. The results showed that males outperformed females in two of the five WCST sub-scores: %Corrects and %Errors. Sex differences in these scores were related to aging, becoming noticeable in those over 60. At the molecular level, differently expressed individual proteins and protein complexes between both sexes are associated with the potential N-methyl-D-aspartate type glutamate receptor (NMDAR)-mediated excitotoxicity, with the NMDAR complex being enriched exclusively in elderly female samples. These findings provided a preliminary indication that healthy Thai females might be more susceptible to such neurotoxicity, as evidenced by their cognitive performance. NMDAR protein complex enrichment in serum could be proposed as a potential indication for predicting cognitive aging in healthy Thai females.
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spelling doaj.art-86eae7cc05ab4382b4a5f06087e302a02024-01-21T12:22:55ZengNature PortfolioScientific Reports2045-23222023-11-0113111510.1038/s41598-023-46750-4Proteomic association with age-dependent sex differences in Wisconsin Card Sorting Test performance in healthy Thai subjectsChen Chen0Bupachad Khanthiyong1Benjamard Thaweetee-Sukjai2Sawanya Charoenlappanit3Sittiruk Roytrakul4Samur Thanoi5Gavin P. Reynolds6Sutisa Nudmamud-Thanoi7Medical Science Graduate Program, Faculty of Medical Science, Naresuan UniversityFaculty of Medicine, Bangkokthonburi UniversitySchool of Medicine, Mae Fah Luang UniversityNational Centre for Genetic Engineering and Biotechnology, National Science and Technology Development AgencyNational Centre for Genetic Engineering and Biotechnology, National Science and Technology Development AgencySchool of Medical Sciences, University of PhayaoBiomolecular Sciences Research Centre, Sheffield Hallam UniversityCentre of Excellence in Medical Biotechnology, Faculty of Medical Science, Naresuan UniversityAbstract Sex differences in cognitive function exist, but they are not stable and undergo dynamic change during the lifespan. However, our understanding of how sex-related neural information transmission evolves with age is still in its infancy. This study utilized the Wisconsin Card Sorting Test (WCST) and the label-free proteomics method with bioinformatic analysis to investigate the molecular mechanisms underlying age-related sex differences in cognitive performance in 199 healthy Thai subjects (aged 20–70 years), as well as explore the sex-dependent protein complexes for predicting cognitive aging. The results showed that males outperformed females in two of the five WCST sub-scores: %Corrects and %Errors. Sex differences in these scores were related to aging, becoming noticeable in those over 60. At the molecular level, differently expressed individual proteins and protein complexes between both sexes are associated with the potential N-methyl-D-aspartate type glutamate receptor (NMDAR)-mediated excitotoxicity, with the NMDAR complex being enriched exclusively in elderly female samples. These findings provided a preliminary indication that healthy Thai females might be more susceptible to such neurotoxicity, as evidenced by their cognitive performance. NMDAR protein complex enrichment in serum could be proposed as a potential indication for predicting cognitive aging in healthy Thai females.https://doi.org/10.1038/s41598-023-46750-4
spellingShingle Chen Chen
Bupachad Khanthiyong
Benjamard Thaweetee-Sukjai
Sawanya Charoenlappanit
Sittiruk Roytrakul
Samur Thanoi
Gavin P. Reynolds
Sutisa Nudmamud-Thanoi
Proteomic association with age-dependent sex differences in Wisconsin Card Sorting Test performance in healthy Thai subjects
Scientific Reports
title Proteomic association with age-dependent sex differences in Wisconsin Card Sorting Test performance in healthy Thai subjects
title_full Proteomic association with age-dependent sex differences in Wisconsin Card Sorting Test performance in healthy Thai subjects
title_fullStr Proteomic association with age-dependent sex differences in Wisconsin Card Sorting Test performance in healthy Thai subjects
title_full_unstemmed Proteomic association with age-dependent sex differences in Wisconsin Card Sorting Test performance in healthy Thai subjects
title_short Proteomic association with age-dependent sex differences in Wisconsin Card Sorting Test performance in healthy Thai subjects
title_sort proteomic association with age dependent sex differences in wisconsin card sorting test performance in healthy thai subjects
url https://doi.org/10.1038/s41598-023-46750-4
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