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Association Between 5-HT/MAOA Gene Polymorphisms And Aggressive Behavior And Experimental Study Of Nutrient Intervention

Posted on:2011-12-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:H F LiuFull Text:PDF
GTID:1114360305453388Subject:Health Toxicology
Abstract/Summary:PDF Full Text Request
With the development of society, the increasing instability, violence attack has become a more and more serious international social problem. Violent attacks cause serious harm to society, which has always been an important factor to undermine the social order and even the social and political stability. The implementation of violent crime can injury the victims' physical and mental health seriously, which also cause social instability. The violence not only violates the principle of social responsibility and worses the stability of social environment, but also is a direct factor induced the increase of crime rates. It can be said that if violent crime can not be effectively curbed, it will directly impede the development of society.Violent crime is an prominent problem of the development of modern social, while violent attacks is an important subject of medical research which has become a hot and difficult medical research. Most studies suggest that violent attack is an interaction resulted from the biological, psychological and social factors. Current scientific researches on violent attacks involve biology, genetics, sociology, psychology, environmental science and other fields. Domestic researches on the offensive have started relatively later and limited, while foreign has accumulated richer research data and obtained more meaningful results. The violent actors are usually highly aggressive actors, and the aggressive behavior is a certain sign of warning on the subsequent violence. So the research of aggressive behavior has a special significance to different animals and humans, which provide some reference for the control and reduction of violent crime. The studies on biological factors of aggressive behavior have prompted that violent crime has obvious biological mechanism, which has a positive significance for the clinical and social. In addition, it also provide biology - Psychology - Sociology of comprehensive prevention and control measures for the effective prevention of violent crime and more scientific basis for guidance for safeguarding the national long-term stability and building a harmonious society.Objectives:This study attempts to use a variety of experimental techniques in a multi-interdisciplinary research to explore the role of complex nutrients in the process of intervention aggressive behavior and the possible mechanism. and to reveal the the impact of nutritional factors on aggressive behavior. This study takes the violent crime population as research objects to study the gene polymorphisms associated with aggressive behavior and provide clues to clarify the genetics, endocrinology, biology and nutrition of aggressive behavior as well as a reference to the control and reduce violent crime.Methods:Using Promega liquid extract DNA purification kits to extract peripheral blood leukocytes in genomic DNA. This study takes bioinformatic approaches for tools and browses the SNPs map for each selected gene through http://www.ncbi.nlm.nih.gov/ database, to choose the five SNPs which contain restriction endonuclease points. We genotyped all 193 collected samples, rs6296, rs6314, rs5906893, rs1137070 4 gene locus are genotyped by using PCR-RFLP method, while rs6323 locus using PCR-SSP method. All the detected results were digitize and input SPSS database, and each SNP allele and genotype frequencies were calculated through the SPSS statistical software.UNPHASED3.0.12 software is applied to do the Trans-phase analysis of the interaction between genes located in different chromosomes. We detected the plasma monoamine oxidase (MAO) activity and total cholesterol (TCH) content using the kit in 64 cases of violent attacks and 69 cases of controls matched with its conditions (see study). We made hamsters with a strong offensive using the solitary raised model, and then apply different doses of the compound nutrients by gavage to intervene their offensive and to observe the basic states of golden hamsters in each group, a variety of behaviors detection indexes and the assessments of aggressive behaviors in each group. Then we detected the NOS activity, MAO activity and the content of monoamine neurotransmitters in brain tissue and the hippocampus, we also analysized the association between them and the aggressive behavior and further extracted total RNA in hippocampal to measure mRNA expression levels, and detected 5-HT2A, 5-HT1B, MAOA protein expression using the Western-blot and immunohistochemical methods.1. The relationship between SNPs site and aggressive behaviorThe genotype distribution of rs6296 located in 5-HT1B gene has no significant difference between the attack group and the control group (P>0.05); The genotype distribution of rs6314 located in 5-HT2A gene has no significant difference between the attack group and the control group (P>0.05); The genotype frequencies distribution of rs5906893, rs1137070 locus, rs6323 located in MAOA gene genotype has no statistically significant difference between in the attack and the control group (P > 0.05).2. The relationships between haplotype and aggressive behaviorTheχ2 test results of haplotype system can be seen: CTT allele of rs5906893,rs1137070,rs6323 haplotype system in MAOA gene may be associated with aggressive behavior (P = 0.015, P<0.05). Other haplotype systems were not associated with the aggressive behavior (P > 0.05).3. The relationship between genes, sites interaction and the attackThe interaction of the G/G genotype of rs6296 in 5-HT1B gene and the T / T genotype of rs5906893 in MAOA gene had significantly different distribution between the attack group and the control group (P = 0.045, P <0.05), which suggested that the interaction between rs6296 and rs5906893 sites may be associated with violent attacks.The allele interaction of rs6296 (C) in 5-HT1B gene, rs6314 (C) in 5-HT2A gene, rs5906893 (T) and rs1137070 (C) in MAOA gene had significant difference in the attacking group and the control group (P = 0.024, P <0.05), which suggested that the interaction of this 3 alleles may be associated with violent attack behaviors. The allele interaction of rs6296 (C) in 5-HT1B gene, rs6314 (T) in 5-HT2A gene, rs5906893 (C), rs1137070 (T) and rs6323 (T) in MAOA gene had significant difference in the attack group and the control group (P = 0.006, P <0.01), which illustrated the interaction of this three alleles may be associated with violent attack behaviors.4. The relationship of Cholesterol levels, MAO activity and SNPs genotype and aggressive behavior.We detected plasma monoamine oxidase (MAO) activity and total cholesterol (TCH) content in 64 cases of violent attacks on staff and 69 controls matched with their conditions (see study). The statistics showed that MAO (P <0.01) had significant difference in the attack group and the control group, while the total cholesterol had no significant difference between the two groups (P > 0.05). To compared the genotypes of each SNPs between the attack group and the control group is whether associated with plasma indicators of MAO activity and TCH concentration or not.The results showed that rs6296 carrying G/C, G/G (P <0.05) genotype of attack group was significantly lower than that of the control group, suggesting that genotype of rs6296 may be associated with aggression and low cholesterol; the MAO activity of attack group carrying rs6296 G/C, C/C was significantly lower than that of the control group (P <0.01), prompted rs6296 genotype may be associated with aggression and low activity MAO. the MAO activity of rs6314 carrying T/T genotype of the attack group was significantly lower than that of the control group (P <0.01); the MAO activity of carrying T/C, C/C genotype of the attack group was lower than the control group, the difference was significant (P <0.05). TCH concentration in the attack group and the control group had no statistically difference between the different genotypes (P >0.05). MAO activity of rs5906893 carrying T/T, C/C genotype of the attack team was significantly lower than the control group (P <0.01). TCH concentration in the attack group and that of the control group had no statistically difference between the different genotypes (P >0.05). rs1137070 carrying T/T, C/C genotype of the attack team MAO activity was significantly lower than that of the control group (P <0.01). TCH concentration in the attack group and the control group had no statistically difference between the different genotypes (P >0.05). MAO activity of rs6323 locus carrying T/T, G/G genotype of the attack team was significantly lower than that of the control group (P <0.01), MAO activity of attack group carrying G/G genotype was lower than the staff carrying T/T genotype, the difference was significant (P <0.05). TCH concentration in the attack group and the control group had no statistically significant difference between the different genotypes (P >0.05).5. The relationship between compound nutrients and the offensive of the solitary golden hamstersThere was significant difference between the offensive of the solitary model group and other groups (P <0.05). The difference of Incubation period of the attack, the number of attacks and attack strength were significant (P <0.05).6. The relationship of complex nutrients and NOS, MAO activity and monoamine neurotransmitters of solitary hamstersNOS and MAO activity among the groups has no significant differences. 5-HT, 5-HIAA levels in brain was lower in the isolated model group, compared with the other groups has significant difference (P <0.05). After adding complex nutrients, each dose group of 5-HT, 5-HIAA levels in the brain tissue were improved, in particular SI + M and SI + H groups. There was significantly difference compared with the SI group (P <0.05). DA levels of Brain tissue is higher in the SI group. After adding complex nutrients, DA content in the brain tissue of each dose group were decreased, especially SI + M, SI + H groups, compared with the SI group the difference was significant (P <0.05).7. The relationship between complex nutrients and the levels of 5-HT2A, MAOA mRNA expression of isolated keep hamstersThe 5-HT2A, MAOA mRNA expression levels of the golden hamsters of solitary model were higher that of the control group, the difference was significant (P <0.01). Adding the compound nutrients can reduce the 5-HT2A, MAOA expression of the solitary raised hamsters, the expression has significant difference between SI + H group and the model group (P<0.01), while there was no significant difference between SI + H group and the control group (P >0.05).8. the relationship between complex nutrients and 5-HT2A, MAOA protein expression of solitary raised hamstersThe results of Western blot and immunohistochemistry is consistent, the 5-HT2A, MAOA expression of isolated hamsters model group was higher than that of the control group, the difference was significant (P<0.01). Adding the compound nutrients can reduce the 5-HT2A, MAOA expression volume of the solitary raise hamsters, the expression has significant difference between SI + H group and the model group(P <0.01), while there was no significant difference between SI + H group and t the control group (P > 0.05).New ideas:1. This study takes the violent crime offenders having full responsibility and the healthy with no criminal records as study objects, applies the case - control group correlation analysis method; combines the molecular genetics and bioinformatics; combines the single site and multiple sites correlation analysis closely; and does association analysis between plasma indicators and genotypes of SNPs and offensive.2. This study observes the effect of using different doses of compound nutrients on the attack behaviors of isolated hamsters for the first time, and determines the brain neurotransmitters (NOS; MAO; DA; 5-HT; 5-HIAA) levels of hamsters, and studies the effects of complex nutrients on 5-HT2A receptor and MAOA in hippocampal of isolated hamsters. evaluation by behavior index, biochemical detection and mRNA level, Western blot (western blot), immunohistochemistry of experimental techniques, this study explores mechanism of the compound nutrients acting on the isolated hamsters attack.3. The type and quantity of complex nutrients are calculated by recommended dose of Children's complex nutrient intake level of the Chinese Nutrition Society (27kg body weight). 4. The strong offensive of the isolated animal model has comparability with human, which can reflect the human attacks. Compared with the previous animal modeling approaches which change animals'physical condition using the stress sources of physiological, unnatural state, such as electric shocks, cold, food and water deprivation, this modeling method is more natural and does not affect their behavioral response, and existes psychological and social factors reaction.
Keywords/Search Tags:Composite nutrients, golden hamster, aggressive behavior, monoamine neurotransmitters, 5-HT, MAOA, single nucleotide polymorphism
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