Comparison Of Cognitive Abilities Of Tibetan Adolescents At Different Altitudes In Tibet And The Relationship With Acetylated Proteomics And Histone Acetylation

Objective:1.To compare the cognitive functions of Tibetan adolescents at different altitudes and studies the influencing factors.2.To screen the differential acetylated proteins involved in the effects of high altitude hypoxia on cognitive functions,analyse their main functions and the signalling pathways involved,compare the histone acetylation sites and speculate on the possible mechanisms,so as to provide new ideas for research on the prevention and treatment of cognitive function impairment caused by chronic plateau hypoxia.Methods:1.The cross-sectional part of the study population consisted of 1056 Tibetan adolescents from four altitude groups.Of these,97 were in the low altitude group(2800m),613 in the high altitude group(Altitude of 4300m or 4500m),227 in the high to low group(migration from 4300m to 2800m)and 119 in the low to high group(migration from2800m to 4300m),with the change in altitude occurring The duration of migration for these students ranged from two months to two years.Fluid intelligence was measured using the Standard Progressive Matrices(SPM).General status was collected using a questionnaire.For the description of count data,frequencies and percentages were used,and for the comparison of rates we used theχ~2test.Means and standard deviations were used to describe the measurement data.Means were compared using analysis of variance or t-tests.Variables with P<0.10 in the univariate analysis were included in the multivariate analysis,Multi-factor analyses were conducted using multilevel linear regression models to determine the effect of altitude and other factors,P<0.05 was used for the significance level.2.After re-administering cognitive tests(SPM,flanker task,n-back test),8 was selected,two higher scoring groups and two low scoring matched for sex age were drawn from each of the 20 respondents at high altitude and 15 respondents at low altitude The differential acetylated proteins in the peripheral leukocytes were identified and analyzed using 4D-LFQ acetylated proteomics technology,GO enrichment analysis and KEGG pathway enrichment analysis was performed to further analyze the related pathways.Results:1.Cross-sectional study In the fixed effects part of the multiple linear regression model,the mean fluid reasoning(SPM)score of low-altitude adolescents who had attended kindergarten was 40.41.High-altitude to low-altitude,high to low group、low-altitude group and low to high group students mean score 2.66,4.71 and 6.70 points lower,respectively,than students from low-altitude group.Students who have attended kindergarten mean score 2.50 points lower than students who did not attend kindergarten.In the random effects component,those with only one grade scored 2.93 points lower on average.Students from the Third County scored 1.89 points higher on average than students from the other three counties.2.A total of 152 acetylated proteins,294 acetylated peptides and 321 acetylation sites were identified.Fifty-five acetylation modification sites were significantly up-regulated 42 significantly down-regulated in the high altitude high cognitive test score group compared to the low cognitive test score groups(P<0.05).10acetylation modification sites significantly up-regulated 161 significantly down-regulated in the low altitude high cognitive test score group compared to the low cognitive test score groups(P<0.05).3.GO enrichment results showed that the main biological processes of differentially acetylated proteins both between high altitude high and low cognitive test score groups and low altitude high and low cognitive test score groups include neutrophil degranulation,hydrogen peroxide catabolic processes,platelet aggregation,classical glycolysis,glycolytic processes,and gluconeogenesis.The main function is protein binding to structural components of the cytoskeleton,etc.4.KEGG enrichment results showed that the most important pathways were glutathione metabolism,glycolysis/gluconeogenesis pathway,HIF-1 pathway,in both high altitude or low altitude,high cognitive test score groups compare with low cognitive test score groups.5.H3K9、H3K14、H3K18,Three loci of histone H3 were significantly up regulated(P<0.05),H4K12、H4K16 two loci of H4were significantly down regulated(P<0.05)in high-altitude high cognitive test score groups compare with low cognitive test score groups.H3K9、H3K14、H3K18、H3K23、H3K79 five loci of H3 were significantly downregulated(P<0.05)in low-altitude high cognitive test score groups compare with low cognitive test score groups.Conclusion:1.High altitude may have a negative impact on the cognition of Tibetan adolescents.This effect may be able to reduced by moving to a lower altitude,increasing the number of years of formal education,attending kindergarten and living in a more urbanized area.Tibetan adolescents living in higher altitude areas should avoid moving to higher altitude areas.2.Cognitive impairment in altitude hypoxia Possibly associated with protein and histone acetylation modifications.