Cholinergic-estrogen interaction is associated with the effect of education on attenuating cognitive sex differences in a Thai healthy population

PLoS One. 2023 Jul 20;18(7):e0278080. doi: 10.1371/journal.pone.0278080. eCollection 2023.

Abstract

The development of human brain is shaped by both genetic and environmental factors. Sex differences in cognitive function have been found in humans as a result of sexual dimorphism in neural information transmission. Numerous studies have reported the positive effects of education on cognitive functions. However, little work has investigated the effect of education on attenuating cognitive sex differences and the neural mechanisms behind it based on healthy population. In this study, the Wisconsin Card Sorting Test (WCST) was employed to examine sex differences in cognitive function in 135 Thai healthy subjects, and label-free quantitative proteomic method and bioinformatic analysis were used to study sex-specific neurotransmission-related protein expression profiles. The results showed sex differences in two WCST sub-scores: percentage of Total corrects and Total errors in the primary education group (Bayes factor>100) with males performed better, while such differences eliminated in secondary and tertiary education levels. Moreover, 11 differentially expressed proteins (DEPs) between men and women (FDR<0.1) were presented in both education groups, with majority of them upregulated in females. Half of those DEPs interacted directly with nAChR3, whereas the other DEPs were indirectly connected to the cholinergic pathways through interaction with estrogen. These findings provided a preliminary indication that a cholinergic-estrogen interaction relates to, and might underpin, the effect of education on attenuating cognitive sex differences in a Thai healthy population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Brain* / growth & development
  • Brain* / physiology
  • Cholinergic Neurons* / physiology
  • Cognition* / physiology
  • Educational Status*
  • Estrogens* / physiology
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Neuropsychological Tests
  • Proteomics
  • Sex Characteristics*
  • Sex Factors
  • Southeast Asian People

Substances

  • Estrogens

Grants and funding

Chen Chen received financial support from the Naresuan Competitive Grants for International Students (NCG) for studying doctoral degree and Sutisa Nudmamud-Thanoi received partial support from the Reinventing University Program 2023, the Ministry of Higher Education, Science, Research and Innovation (MHESI), Thailand (R2566A044), and the NCG grant has no grant number provided. The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.