OBJECTIVE: The etiology of attention deficit hyperactivity disorder (ADHD) has not been entirely clarified yet. Structural and metabolic differences at the prefrontal striatal cerebellary system and the interaction of gene and environment are the main factors that thought to play roles in the etiology. Genetic investigations are performed especially about the dopamine pathways and receptors. In this study; it was aimed to investigate the association of the synaptobrevin-2 (VAMP-2) gene Ins/Del polymorphism and syntaxin 1A gene intron 7 polymorphism, which take place in encoding presynaptic protein, with adult ADHD. METHODS: One hundred thirty-nine patients, having ADHD aging between 18 and 60 years and 106 healthy people as controls were included into the study. DNA samples were extracted from whole blood and genetic analysis were performed. RESULTS: A significant difference was determined between ADHD and VAMP-2 Ins/Del polymorphism and syntaxin 1A intron 7 polymorphism according to the control group. These polymorphisms were found not to be associated with subtypes of ADHD. CONCLUSION: It is supposed that synaptic protein genes together with dopaminergic genes might have roles in the etiology of ADHD.
Adult* ; Aging ; Attention Deficit Disorder with Hyperactivity* ; DNA ; Dopamine ; Humans ; Introns ; Qa-SNARE Proteins* ; Syntaxin 1* ; Vesicle-Associated Membrane Protein 2*

AIMTo investigate the action and mechanism of Syn-1A in reversing the activation of K(ATP) channel induced by weak acidic pH.

METHODSThe patches excised from Kir6.2/SUR2A expressing HEK-293 cells were used to establish inside-out configuration. To examine the actions of weak acidic pH in activation of the channel and the reverse action of Syn-1A on it, the inside-out patches were continuously perfused with the solution of pH from 7.4, 7.0, 6.8, 6.5 to 6.0 with or without Syn-1A. In vitro binding was employed to study the influence of different pH to the binding of Syn-1A to SUR2A subunit.

RESULTSSyn-1A blocked pH 6.5, 6.8 and 7.0 induced activation of the channel, and Syn-1A binding to SUR2A were increased by reducing pH from 7.4 to 6.0.

CONCLUSIONSyn-1A would assert some inhibition of the KATP channels, which might temper the fluctuation of acidic pH-induced K(ATP) channel opening that could induce fatal re-entrant arrhythmias.

HEK293 Cells ; Humans ; Hydrogen-Ion Concentration ; KATP Channels ; metabolism ; Patch-Clamp Techniques ; Potassium Channels ; metabolism ; Potassium Channels, Inwardly Rectifying ; metabolism ; Syntaxin 1 ; pharmacology

Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder characterized by hyperactivity, inattention and increased impulsivity. In recent years, a large number of genetic studies for ADHD have been published and related genetic data has been accumulated dramatically. To provide researchers a comprehensive ADHD genetic resource, we previously developed the first genetic database for ADHD (ADHDgene). The abundant genetic data provides novel candidates for further study. Meanwhile, it also brings new challenge for selecting promising candidate genes for replication and verification research. In this study, we surveyed the computational tools for candidate gene prioritization and selected five tools, which integrate multiple data sources for gene prioritization, to prioritize ADHD candidate genes in ADHDgene. The prioritization analysis resulted in 16 prioritized candidate genes, which are mainly involved in several major neurotransmitter systems or in nervous system development pathways. Among these genes, nervous system development related genes, especially SNAP25, STX1A and the gene-gene interactions related with each of them deserve further investigations. Our results may provide new insight for further verification study and facilitate the exploration of pathogenesis mechanism of ADHD.
Attention Deficit Disorder with Hyperactivity ; genetics ; Computer Simulation ; Databases, Genetic ; Gene Regulatory Networks ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Models, Genetic ; Software ; Synaptosomal-Associated Protein 25 ; genetics ; Syntaxin 1 ; genetics

OBJECTIVE: Synaptic vesicle mobilization and neurite outgrowth regulation molecules were examined in modulation of effects of methylphenidate (MPH) in Spontaneous Hypertensive Rats (SHRs), a model for attention-deficit hyperactivity disorder (ADHD). METHODS: We compared the changes in the protein expression level of Cyclin dependent kinase 5 (Cdk5) and molecular substrates of Cdk5; tropomyosin receptor kinase B (TrkB), syntaxin 1A (STX1A) and synaptosomal-associated protein 25 (SNAP25). Comparisons were made in prefrontal cortex of vehicle (distilled water i.p. for 7 days)-treated SHRs, vehicle-treated Wistar Kyoto Rats (WKYs) and MPH (2 mg/kg i.p. for 7 days) treated SHRs. RESULTS: The Cdk5 level of vehicle-treated SHRs was significantly decreased compared to the Cdk5 level of vehicle-treated WKY rats, but was restored to the expression level of vehicle-treated WKYs in MPH-treated SHR. The ratio of p25/p35 was significantly decreased in MPH-treated SHR compared to vehicle-treated SHR. Moreover, TrkB, STX1A and SNAP25 of vehicle-treated SHRs were significantly decreased compared to vehicle-treated WKY rats, but were restored to the expression level of vehicle-treated WKYs in MPH-treated SHR. CONCLUSION: The results show that Cdk5, TrkB, STX1A, and SNAP25 were involved in the modulation of MPH effects in prefrontal cortex of SHRs and play important role in treatment of ADHD.
Animals ; Cyclin-Dependent Kinase 5 ; Methylphenidate ; Neurites ; Phosphotransferases ; Prefrontal Cortex ; Rats ; Rats, Inbred WKY ; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins ; Synaptic Vesicles ; Synaptosomal-Associated Protein 25 ; Syntaxin 1 ; Tropomyosin ; Water