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Serotonin Biosynthesis (serotonin + biosynthesis)
Selected AbstractsGENETIC STUDY: Tryptophan hydroxylase 2 gene and alcohol use among college studentsADDICTION BIOLOGY, Issue 3-4 2008Paul Gacek ABSTRACT Genes that regulate serotonin activity are regarded as promising predictors of heavy alcohol use. Tryptophan hydroxylase (TPH2) plays an important role in serotonergic neurotransmission by serving as the rate-limiting enzyme for serotonin biosynthesis in the midbrain and serotonergic neurons. Despite the link between TPH2 and serotonergic function, TPH2's role in the pathogenesis of alcohol-use disorders remains unclear. The goal of this study was to examine whether a variation in the TPH2 gene is associated with risky alcohol consumption. Specifically, this study examined whether the TPH2 G-703T polymorphism predicted alcohol consumption among college students. In two successive years, 351 undergraduates were asked to record their alcohol use each day for 30 days using an Internet-based electronic diary. Participants' DNA was collected and polymerase chain reaction genotyping was performed. Results show that alcohol consumption was not associated with the TPH2 G-703T polymorphism alone, or the interaction of TPH2 with two other candidate polymorphisms (TPH1 C218A and the SLC6A4 tri-allelic 5-HTTLPR), or negative life events. In conclusion, this study supports recent null findings relating TPH2 to drinking outcomes. It also extends these findings by showing null interactions with the TPH1 C218A polymorphism, the SLC6A4 tri-allelic 5-HTTLPR polymorphism and environmental stressors in predicting sub-clinical alcohol use among Caucasian American young adults. [source] Association of tryptophan hydroxylase gene polymorphism with depression, anxiety and comorbid depression and anxiety in a population-based sample of postpartum Taiwanese womenGENES, BRAIN AND BEHAVIOR, Issue 6 2004H. S. Sun Depression and anxiety disorders often coexist clinically and both are known to have a genetic basis, but the mode of inheritance is too complicated to be determined so far. Serotonin is the biogenic amine neurotransmitter most commonly associated with depression and anxiety. Since tryptophan hydroxylase (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, its role in the pathophysiology of these psychiatric diseases has been intensively studied. In this study, we examined whether polymorphism of the TPH1 gene is related to the etiology of major depression, anxiety and comorbid depression and anxiety. Five single nucleoside polymorphisms of the TPH1 gene were studied in a population-based sample of postpartum Taiwanese women consisting of 120 subjects with depression or/and anxiety and 86 matched normal controls. A significant difference (P = 0.0107) in genotype frequency for the T27224C polymorphism was found between the comorbid and normal groups, and risk analysis showed that the C allele conferred a strong protective effect (odds ratio = 0.27; 95% confident interval = 0.11,0.7). Three-allele haplotypes involving T27224C polymorphism were constructed and haplotype associations between particular haplotype combinations and various diseases identified. However, the associations were weak and the overall haplotype frequency profiles in all groups were similar. The results suggest that depression, anxiety, and comorbid depression and anxiety disorders may have related etiologies. In addition, this study suggests that the TPH1 gene might play a role in the pathogenesis of these closely related disorders. [source] Plasma 5-Hydroxytryptamine (5-HT) in Migraine During an Attack-Free PeriodHEADACHE, Issue 4 2006Eiichiro Nagata MD Objective.,We measured the plasma 5-HT, 5-hydroxytryptophan (5-HTP), and tryptophan levels in controls, migraine patients with aura (MWA), and migraine patients without aura (MWoA) during an attack-free period. Background.,Serotonin (5-hydroxytryptamine, 5-HT) has been implicated in the pathophysiology of migraine. The precise relationship between 5-HT and migraine, however, remains unclear. Methods.,Blood samples in controls, MWA, and MWoA patients during an attack-free period were collected from brachial arteries and analyzed using HPLC. Results.,The plasma tryptophan and 5-HTP levels were not significantly different between the controls and migraine patients (either MWA or MWoA). However, the plasma 5-HT level in the MWA patients was significantly lower than that in the controls and MWoA patients. Conclusions.,The present data suggest that reduced levels of 5-HT in MWA may result from either a dysfunction in the enzymes involved in serotonin biosynthesis or a dysfunction in 5-HT release or uptake from platelets and lymphocytes. These findings indicate the existence of a serotonin metabolism dysfunction in MWA patients that may differ from the state of serotonin metabolism in MWoA patients. [source] Serotonin receptors antagonistically modulate Caenorhabditis elegans longevityAGING CELL, Issue 4 2007Hana Murakami Summary The neurotransmitter serotonin has been implicated in affecting the variation of longevity in natural Drosophila populations and age-related diseases in mammals. Based on these observations, it has been predicted that serotonin signal, perhaps at levels of serotonin biosynthesis, may control lifespan. Here, we investigated a variety of mutations in serotonin-signal genes, including serotonin biosynthesis genes, a serotonin transporter gene, and serotonin receptor genes. Despite this prediction, mutations in the serotonin biosynthesis genes had little or modest effects on lifespan, while the mod-5 mutation with increased availability of serotonin caused a modest life-shortening effect. In contrast, a deletion mutation of the ser-1 serotonin receptor gene increased longevity by up to 46%, likely through the insulin/insulin-like growth factor 1 pathway. This result suggests an interaction between the serotonin pathway and the insulin/insulin-like growth factor 1 pathway. A deletion mutation of another serotonin receptor gene, ser-4, shortened early to mid lifespan. The results suggest that serotonin signal antagonistically modulates longevity through different serotonin receptors. This study may indicate serotonin receptors as a potential target for antigeric interventions. 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