ABSTRACT
Objective To analyze the influence of sleep deprivation on expression of serotonin receptor 1A(5-HT1A) and dopanine-2 receptor (D2R) gene and to explore the differences between different neurotransmitter pathways involved in sleep regulation through measuring the gene expression of 5-HT1A and D2R in regions of hippocampus,hypothalamus and striatum with different sleep deprivation models.Methods Sleep deprivation was performed to male SD rats of 10-week-old for 24 hours,48 hours and 72 hours respectively as the experimental group and a control group was taken for comparison.The expressions of 5-HT1A and D2R gene in regions of hippocampus,hypothalamus and striatum were detected through RT-PCR technique to analyze the influence of sleep deprivation on gene expression in different regions.Results Sleep deprivation had a significant effect on the gene expression of 5-HT1A in regions of hippocampus and striatum(F=56.203,P＜0.01 ; F=77.288,P＜0.01).The three experimental groups were all superior to the control group and the difference was of statistic significance(P＜0.05).In the hippocampus region,the expression quantity of the 72 hours group(0.618±0.054) was superior to that of the 24 hours group and of the 48 hours group(24 hours:0.404±0.023,P＜0.01 ;48 hours:0.455±0.042.P＜0.05).In the striatum region,the differences between the 24 hours group(0.413±0.033),the 48 hours group(0.464±0.034)and the 72 hours group(0.610±0.040) were all of statistic significance(all P＜0.05).Sleep deprivation had a significant effect on the expression of D2R gene in regions of hippocampus and striatum(F=74.708,P＜0.01 ; F=80.687,P＜0.01).The expression quantity of the three experimental groups in regions of hippocampus (24 hours:0.386±0.027,48 hours:0.318±0.014,72 hours:0.250±0.010) and striatum(24 hours:0.396±0.013,48 hours:0.349±0.017,72 hours:0.260±0.013) were all inferior to the control group.The differences were of statistic significance (all P＜0.05).There was a negative correlation between the gene expressions of 5-HT1A and D2R of rats of the three experience groups(all P＜0.05).Conclusion For the sleep deprivation rats,the gene expression of 5-HT1A rises while that of D2R falls in regions of hippocampus,hypothalamus,and there is a negative correlation between the expressions of the two genes.
ABSTRACT
OBJECTIVE: Dysfunction of serotonin 1A receptors (HTR1A) may play a role in the genesis of suicidal behavior. We studied the association between a functional polymorphism in the HTR1A gene and suicidal behavior. METHOD: We performed a meta-analysis of published genetic association studies by searching through Medline, PubMed, and Web of Science databases to analyze a possible correlation between the rs6295 polymorphism and suicidal behavior in different populations. RESULTS: Four studies comprising a total of nine hundred and fifty seven patients with suicidal behavior and nine hundred and fifty seven controls were the eligible. The G allele of the rs6295 polymorphism may not be associated with suicidal behavior (Random-effects model: OR = 1.08; 95 percent CI: 0.80-1.45; p(Z) = 0.80) in presence of heterogeneity (Q = 17.84, df = 4, p = 0.0013). In a second analysis that presented no heterogeneity, a negative association was also observed (OR = 0.94; 95 percentCI: 0.79-1.13; p(Z) = 0.99). CONCLUSION: To our knowledge, the present study is the first meta-analysis searching for a correlation between rs6295 of HTR1A and suicidal behavior. Our results showed no association between HTR1A and suicidal behavior. However, more studies assessing different populations, as well as larger samples, are needed.
OBJETIVO: É possível que uma disfunção nos receptores 1A de serotonina (HTR1A) desempenhe um papel na origem do comportamento suicida. Estudamos a associação entre um polimorfismo funcional no gene HTR1A e comportamento suicida. MÉTODO: Realizamos uma metanálise de estudos de associação genética já publicados através de uma busca nos banco de dados do Medline, PubMed e Web of Science para identificar uma possível correlação entre o polimorfismo rs6295 e comportamento suicida em diferentes populações. RESULTADOS: Foram selecionados quatro estudos com um total de 957 pacientes com comportamento suicida e 957 controles. O alelo G do polimorfismo rs6295 não pôde ser associado a comportamento suicida (modelo de efeitos aleatórios: OR = 1,08; 95 por centoCI: 0,80-1,45; p(Z) = 0,80) na presença de heterogeneidade (Q = 17,84, df = 4, p = 0,0013). Em uma segunda análise, sem heterogeneidade, também foi observada uma associação negativa (OR = 0,94; 95 por centoCI: 0,79-1,13; p(Z) = 0,99). CONCLUSÃO: Pelo que nos consta, trata-se da primeira metanálise cujo objetivo é identificar uma correlação entre o polimorfismo rs6295 do HTR1A e comportamento suicida. Os nossos resultados não demonstraram existir uma correlação entre o HTR1A e comportamento suicida. No entanto, são necessários estudos adicionais que incluam outras populações, assim como amostras maiores.