ABSTRACT
Transcription factor AP-2beta has been suggested to influence brain monoaminergic systems by regulating target genes. In order to explore a possible functional role, AP-2beta genotype was analysed in relation to striatal dopamine D2 receptor density determined in vivo by positron emission tomography in human subjects (n = 52). The AP-2beta genotype was also analysed in relation to cerebrospinal fluid (CSF) concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) in healthy human subjects (n = 90). There was no association between the AP-2beta genotype and measures of dopamine receptor density, or CSF 5-HIAA concentrations. However, AP-2beta genotype was associated with CSF-levels of HVA (in women) and MHPG. These data may suggest a functional involvement of AP-2beta in the dopaminergic system, but should be interpreted with caution until replicated.
Subject(s)
Biogenic Amines/cerebrospinal fluid , Corpus Striatum/metabolism , DNA-Binding Proteins/genetics , Receptors, Dopamine D2/metabolism , Transcription Factors/genetics , Adult , Analysis of Variance , Autoradiography , Female , Genotype , Humans , Hydroxyindoleacetic Acid/cerebrospinal fluid , Male , Methoxyhydroxyphenylglycol/cerebrospinal fluid , Raclopride/pharmacokinetics , Reference Values , Sweden , Transcription Factor AP-2 , Tritium , White PeopleABSTRACT
Imbalances in the midbrain monoaminergic systems have been implicated to play a role in neuropsychiatric conditions. Several genes in these systems have binding sites for transcription factor activating protein-2 (AP-2) in their regulatory regions. Thus, AP-2 may be a factor controlling the expression of genes in the monoaminergic systems important for maintaining normal psychiatric functions. The present study indicates that subchronic treatment with the antidepressant citalopram induces time-dependent changes in DNA-binding activity and levels of transcription factor AP-2 in rat whole brain. Rats were treated with citalopram (10 mg/kg) for 1, 3, 7 and 21 days. Animals treated for 7 days had significantly decreased DNA-binding activity and levels of AP-2 alpha and AP-2 beta isoforms when compared to saline-treated animals. There was no observed difference between citalopram- and saline-treated animals after 21 days. Elucidation of the molecular mechanisms underlying mental disorders is important for future drug development, where transcription factors might be important drug targets.
Subject(s)
Antidepressive Agents/pharmacology , Brain/drug effects , Citalopram/pharmacology , DNA-Binding Proteins/biosynthesis , Gene Expression/drug effects , Transcription Factors/biosynthesis , Animals , Brain/metabolism , DNA-Binding Proteins/analysis , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Electrophoretic Mobility Shift Assay/methods , Enzyme-Linked Immunosorbent Assay/methods , Gene Expression/physiology , Male , Nuclear Proteins/drug effects , Nuclear Proteins/metabolism , Rats , Rats, Sprague-Dawley , Time Factors , Transcription Factor AP-2 , Transcription Factors/analysis , Transcription Factors/geneticsABSTRACT
Among theories of biological underpinnings to personality traits, different mechanisms of the serotonergic system are perhaps the most common factors suggested to influence individual differences in personality traits. We have investigated two frequent variants in the serotonin 2A receptor gene (5-HT2A) and personality traits. Healthy Swedish subjects (n = 304) were assessed with the Karolinska Scales of Personality (KSP) inventory. After correction for multiple testing, no significant differences were found. We conclude that the investigated 5-HT2A gene variants do not significantly influence personality as assessed by the KSP in the present population.
Subject(s)
Genetic Variation , Receptors, Serotonin/genetics , Adult , Female , Humans , Interviews as Topic , Male , Middle Aged , Personality/genetics , Personnel, Hospital , Receptor, Serotonin, 5-HT2A , Reverse Transcriptase Polymerase Chain Reaction , Students , Surveys and QuestionnairesABSTRACT
Platelet monoamine oxidase B (MAO; EC 1.4.3.4.) activity is stable in the individual and is mainly genetically regulated. Levels of MAO-B in platelets have repeatedly been shown to be associated with personality traits. We have recently also demonstrated an association between the genotype of AP-2beta to a variety of personality traits as well as binge-eating disorder. In the present study we have analysed blood samples from 158 males and 64 females with regard to platelet MAO activity and genotype of transcription factor AP-2beta. In both sexes homozygotes for the long allele [CAAA](5) were significantly associated with low platelet MAO activity P<0.0001 (males) and P=0.0158 (females). This study represents a novel approach to increase the understanding about the molecular mechanisms for how the MAOB gene is regulated in blood cells and how this regulation is linked to personality traits.