Catechol-O-Methyltranferase (COMT) plays a crucial role in the removal of cortical dopamine and is strongly implicated in human executive function. Numerous studies have reported associations of the COMT Val158Met (rs4680) polymorphism with executive function in healthy subjects. However, little work has investigated this in the Thai population and the relationship of age and education with this association remains unclear. Therefore, this study was designed to investigate the association of this polymorphism of the COMT gene with executive cognitive brain function in healthy subjects and the relationship with age and education. The Wisconsin Card Sorting Test (WCST) was performed to assess executive function in 254 healthy Thai subjects (aged 20-72 years). The results showed a significant association of rs4680 with executive function, in which Val/Met heterozygotes demonstrated better cognitive set shifting performance. Moreover, Met allele carriers showed a significantly stronger effect in the categories completed score than did Val homozygotes. Furthermore, age and education also showed a significant association with COMT genotype and WCST. These results revealed that executive cognitive function is associated with COMT genotype and influenced by age and/or education level in a Thai sample.
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 a sex difference 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 level. 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 implied that Cholinergic-estrogen interaction underpins the effect of education on attenuating cognitive sex differences in a Thai healthy population.
Intact cognitive function is dependent on the precise exchange of information between neurons. Sex differences in cognitive function exist, but they are not stable, undergoing 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 was designed to investigate the molecular mechanisms underlying age-related sex differences in cognitive function in a Thai healthy population, as well as to determine the sex-dependent protein complexes for predicting cognitive aging. The Wisconsin Card Sorting Test (WCST) was performed to assess cognitive function in 199 Thai healthy subjects (aged 20–70 years). The results showed that males outperformed females in two of the five WCST sub-scores: %Corrects and %Errors, with a higher percentage of total corrects and a lower total errors rate. Sex differences in these scores were related to aging, and it became noticeable in those over 60. Moreover, the label-free proteomics method and bioinformatic analysis were also used to investigate the age-related alternations in the expression profiles of sex-specific neurotransmission-related proteins. According to the findings, differently expressed individual proteins and protein complexes between Thai healthy men and women were related to the potential excitotoxicity induced by N-methyl-D-aspartate type glutamate receptor (NMDAR) hyperfunction, with females might be more susceptible to such neurotoxicity, as indicated by their cognitive performance. The NMDAR complex was enriched exclusively in elderly female samples, implying that later in life, higher than optimal levels of NMDARs function and loss of estrogen neuroprotective, resulted in a loss of brain environment homeostasis and impaired cognitive function in elderly female subjects. This could explain why the sex differences in %Corrects and %Errors were only significant in the elderly group, and NMDAR protein complex enrichment in serum could be suggested as a potential indication for predicting cognitive aging in Thai healthy females.
Chronic stress (CS) can contribute to dysfunction in several organs including liver and kidney. This study was performed to investigate the changes in serum biochemistry, histological structure, as well as in localization of tyrosine phosphorylated proteins (TyrPho) and Heat shock protein 70 (Hsp-70) in liver and kidney tissues of CS rats induced by two stressors (restrained and force swimming) for 60 consecutive days. Samples of blood, liver, and kidney were collected from adult male Sprague–Dawley rats in each group. Our results showed that serum biochemical parameters including corticosterone, blood sugar, urea nitrogen, creatinine, cholesterol, triglyceride, HDL-C, LDL-C, ALT, AST, alkaline phosphatase in CS group were significantly different from that in normal group in both liver and kidney tissues. Although histological structure was not changed. TyrPho expression was significantly increased in liver lysate but significantly decreased in kidney. Hsp-70 expression in liver increased whereas in kidney decreased. In conclusion, CS can induce changes in liver and kidney functions.
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