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Serotonin Synthesis (serotonin + synthesis)
Kinds of Serotonin Synthesis Selected AbstractsAlterations in Brain Serotonin Synthesis in Male Alcoholics Measured Using Positron Emission TomographyALCOHOLISM, Issue 2 2009Masami Nishikawa Background:, A consistent association between low endogenous 5HT function and high alcohol preference has been observed, and a number of serotonergic manipulations (uptake blockers, agonists) alter alcohol consumption in animals and humans. Studies have also shown an inverse relationship between alcohol use and cerebrospinal fluid levels of serotonin metabolites, suggesting that chronic alcohol consumption produces alterations in serotonin synthesis or release. Methods:, The objective of the study was to characterize regional brain serotonin synthesis in nondepressed chronic alcoholics at treatment entry in comparison to normal nonalcoholic controls using PET and the tracer ,-[11C]-methyl- l -tryptophan. Results:, Comparisons of the alcoholics and controls by SPM found that there were significant differences in the rate of serotonin synthesis between groups. Serotonin synthesis was significantly lower among alcoholics in Brodmann Area (BA) 9, 10, and 32. However, serotonin synthesis among the alcoholics group was significantly higher than controls at BA19 in the occipital lobe and around the transverse temporal convolution in the left superior temporal gyrus (BA41). In addition, there were correlations between regional serotonin synthesis and a quantity-frequency measure of alcohol consumption. Regions showing a significant negative correlation with QF included the bilateral rectus gyri (BA11) in the orbitofrontal area, the bilateral medial frontal area (BA6), and the right amygdala. Conclusions:, Current alcoholism is associated with serotonergic abnormalities in brain regions that are known to be involved in planning, judgment, self-control, and emotional regulation. [source] Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafted with foetal raphe neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2000Jean Michel Brezun Abstract The long-term effects of hippocampal serotonergic denervation and reinnervation by foetal raphe tissue were examined in the dentate gyrus where neurons are continously born in the adult. Complete lesion of serotonin neurons following injections of 5,7-dihydroxytryptamine in the dorsal and medial raphe nuclei produced long-term decreases in the number of newly generated granule cells identified with 5-Bromo-2,-deoxyuridine (BrdU) and the polysialylated form of neural cell adhesion molecule (PSA-NCAM) immunostaining, as observed in 2-month-survival rats. The raphe grafts, but not the control grafts of embryonic spinal tissue, reversed the postlesion-induced decreases in the density of BrdU- and PSA-NCAM-labelled cells detected in the granule layer. Inhibition of serotonin synthesis in animals with raphe grafts reversed back to lesion-induced changes in granule cell proliferation. Furthermore, extensive serotonergic reinnervation of the dentate gyrus in the area proximal to the raphe graft could be associated with supranormal density of BrdU-labelled cells. These results indicate that serotonin may be considered a positive regulatory factor of adult granule cell proliferation. Finally, the lack of effect of embryonic nonserotonergic tissue grafted to serotonin-deprived rats suggests that neurotrophic factors may not be involved in the effects of serotonin on adult neurogenesis. [source] Distribution of the C1473G polymorphism in tryptophan hydroxylase 2 gene in laboratory and wild miceGENES, BRAIN AND BEHAVIOR, Issue 5 2010D. V. Osipova The neurotransmitter serotonin is implicated in the regulation of various forms of behavior, including aggression, sexual behavior and stress response. The rate of brain serotonin synthesis is determined by the activity of neuronal-specific enzyme tryptophan hydroxylase 2. The missense C1473G substitution in mouse tryptophan hydroxylase 2 gene has been shown to lower the enzyme activity and brain serotonin level. Here, the C1473G polymorphism was investigated in 84 common laboratory inbred strains, 39 inbred and semi-inbred strains derived from wild ancestors (mostly from Eurasia) and in 75 wild mice trapped in different locations in Russia and Armenia. Among all the classical inbred strains studied, only substrains of BALB/c, A and DBA, as well as the IITES/Nga and NZW/NSlc strains were homozygous for the 1473G allele. In contrast to laboratory strains, the 1473G allele was not present in any of the samples from wild and wild-derived mice, although the wild mice varied substantially in the C1477T neutral substitution closely linked to the C1473G polymorphism. According to these results, the frequency of the 1473G allele in natural populations does not exceed 0.5%, and the C1473G polymorphism is in fact a rare mutation that is possibly eliminated by the forces of natural selection. [source] Rotenone selectively kills serotonergic neurons through a microtubule-dependent mechanismJOURNAL OF NEUROCHEMISTRY, Issue 1 2007Yong Ren Abstract As a major co-morbidity of Parkinson's disease (PD), depression is associated with the loss of serotonergic neurons. Our recent study has shown that midbrain dopaminergic neurons are particularly vulnerable to microtubule-depolymerizing agents including rotenone, an environmental toxin linked to PD. Here we show that rotenone also selectively killed serotonergic neurons in midbrain neuronal cultures. Its selective toxicity was significantly decreased by the microtubule-stabilizing drug taxol and mimicked by microtubule-depolymerizing agents such as colchicine and nocodazole. Microtubule depolymerization induced by rotenone or colchicine caused vesicle accumulation in the soma and killed serotonergic neurons through a mechanism dependent on serotonin metabolism in the cytosol. Blocking serotonin synthesis or degradation, as well as application of antioxidants, significantly reduced the selective toxicity of rotenone or colchicine. Inhibition of vesicular sequestration of serotonin exerted a selective toxicity on serotonergic neurons that was mitigated by blocking serotonin metabolism. Over-expression of parkin, a protein-ubiquitin E3 ligase that strongly binds to microtubules, greatly attenuated the selective toxicity of rotenone or colchicine. The protective effects of parkin were abrogated by its PD-linked mutations. Together, our results suggest that rotenone and parkin affect the survival of serotonergic neurons by impacting on microtubules in opposing manners. [source] Quantitative measurement of serotonin synthesis and sequestration in individual live neuronal cellsJOURNAL OF NEUROCHEMISTRY, Issue 5 2005J. Balaji Abstract Synthesis and subsequent sequestration into vesicles are essential steps that precede neurotransmitter exocytosis, but neither the total neurotransmitter content nor the fraction sequestered into vesicles have been measured in individual live neurons. We use multiphoton microscopy to directly observe intracellular and intravesicular serotonin in the serotonergic neuronal cell line RN46A. We focus on how the relationship between synthesis and sequestration changes as synthesis is up-regulated by differentiation or down-regulated by chemical inhibition. Temperature-induced differentiation causes an increase of about 60% in the total serotonin content of individual cells, which goes up to about 10 fmol. However, the number of vesicles per cell increases by a factor of four and the proportion of serotonin sequestered inside the vesicles increases by a factor of five. When serotonin synthesis is inhibited in differentiated cells and the serotonin content goes down to the level present in undifferentiated cells, the sequestered proportion still remains at this high level. The total neurotransmitter content of a cell is, thus, an unreliable indicator of the sequestered amount. [source] Regional brain serotonin synthesis is increased in the olfactory bulbectomy rat model of depression: an autoradiographic studyJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Arata Watanabe Abstract Serotonin synthesis rates were evaluated using ,-[14C]methyl- l -tryptophan (,-MTrp) autoradiographic methods in olfactory bulbectomized (OBX) rats. They were significantly (p < 0.05) increased in the frontal (50%) and parietal (40%) cortices, superior olive (over 30%), and the substantia nigra (30%) in the OBX rats as compared to the sham operated animals. There were also increases in 5-hydroxytryptamine (5-HT) synthesis in some limbic areas: the cingulate (32%), the medial forebrain bundle (58%), the hippocampus (13,25%) and the thalamus (22,40%). The largest increase in 5-HT synthesis after OBX was observed in the sensory-motor cortex (67%). 5-HT synthesis rates were significantly decreased in the dorsal and medial raphe nuclei, but there was no significant change the ventral tegmental area and the locus coeruleus following OBX. These results indicate that olfactory bulbectomy causes an imbalance in 5-HT synthesis in some projection areas by disproportionally increasing 5-HT synthesis rates in specific brain regions and making more 5-HT available for neurotransmission. This imbalance in 5-HT synthesis and the subsequent elevation of tissue 5-HT may be responsible for the creation of non-physiological circuitry which may, in part, be reflected in the symptoms resembling human depression. [source] C1473G polymorphism in mouse tph2 gene is linked to tryptophan hydroxylase-2 activity in the brain, intermale aggression, and depressive-like behavior in the forced swim testJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2009Daria V. Osipova Abstract Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme of brain serotonin synthesis. The C1473G polymorphism in the mouse tryptophan hydroxylase-2 gene affects the enzyme's activity. In the present study, we investigated the linkage between the C1473G polymorphism, enzyme activity in the brain, and behavior in the forced swim, intermale aggression, and open field tests using mice of the C57BL/6 (C/C) and CC57BR/Mv (G/G) strains and the B6-1473C (C/C) and B6-1473G (G/G) lines created by three successive backcrossings on C57BL/6. Mice of the CC57BR/Mv strain had decreased brain enzyme activity, aggression intensity, and immobility in the forced swim test, but increased locomotor activity and time spent in the central part of the open field arena compared with animals of the C57BL/6 strain. Mice of the B6-1473G line homozygous for the 1473G allele had lower TPH2 activity in the brain, aggression intensity, and immobility time in the forced swim test compared with animals of the B6-1473C line homozygous for the 1473C allele. No differences were found between the B6-1473G and B6-1473C mice in locomotor activity and time spent in the central part of the arena in the open field test. Thus, the C1473G polymorphism is involved in the determination of TPH2 activity and is linked to aggression intensity and forced-swim immobility in mice. At the same time, the polymorphism does not affect locomotion and anxiety-related behavior in the open field test. The B6-1473C and B6-1473G mice represent a valuable experimental model for investigating molecular mechanisms of serotonin-related behavior. © 2008 Wiley-Liss, Inc. [source] Alterations in Brain Serotonin Synthesis in Male Alcoholics Measured Using Positron Emission TomographyALCOHOLISM, Issue 2 2009Masami Nishikawa Background:, A consistent association between low endogenous 5HT function and high alcohol preference has been observed, and a number of serotonergic manipulations (uptake blockers, agonists) alter alcohol consumption in animals and humans. Studies have also shown an inverse relationship between alcohol use and cerebrospinal fluid levels of serotonin metabolites, suggesting that chronic alcohol consumption produces alterations in serotonin synthesis or release. Methods:, The objective of the study was to characterize regional brain serotonin synthesis in nondepressed chronic alcoholics at treatment entry in comparison to normal nonalcoholic controls using PET and the tracer ,-[11C]-methyl- l -tryptophan. Results:, Comparisons of the alcoholics and controls by SPM found that there were significant differences in the rate of serotonin synthesis between groups. Serotonin synthesis was significantly lower among alcoholics in Brodmann Area (BA) 9, 10, and 32. However, serotonin synthesis among the alcoholics group was significantly higher than controls at BA19 in the occipital lobe and around the transverse temporal convolution in the left superior temporal gyrus (BA41). In addition, there were correlations between regional serotonin synthesis and a quantity-frequency measure of alcohol consumption. Regions showing a significant negative correlation with QF included the bilateral rectus gyri (BA11) in the orbitofrontal area, the bilateral medial frontal area (BA6), and the right amygdala. Conclusions:, Current alcoholism is associated with serotonergic abnormalities in brain regions that are known to be involved in planning, judgment, self-control, and emotional regulation. [source] Effect of Tryptophan Depletion on Alcohol Cue-Induced Craving in Abstinent Alcoholic PatientsALCOHOLISM, Issue 8 2001Ismene L. Petrakis Background: The capacity of alcohol cues to precipitate the desire to drink may be an important determinant of relapse to alcohol use in recovering alcohol-dependent patients. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the magnitude of cue-induced craving for alcohol in recently abstinent alcoholic individuals. Methods: Alcohol-dependent patients (n= 16), 1 to 3 months after detoxification, who exhibited a 20% or greater increase in reported craving when presented with an alcoholic beverage, completed two additional alcohol cue-exposure test days, 1 week apart. Each cue exposure was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion, no tryptophan supplementation) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double-blind fashion. Results: There were no significant changes in the magnitude of cue-induced craving with active tryptophan depletion compared with placebo. Conclusions: These data question the dependence of alcohol cue-induced craving in sober alcoholics on the ongoing synthesis of serotonin. [source] | ||||||||||