http://precedings.nature.com/tags/dopamine Recently posted documents tagged with 'dopamine' Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/3896/version/1 Although there is evidence for the involvement of genes of serotonergic and dopaminergic systems in the manifestation of the Behavioural and Psychological Symptoms in Dementia (BPSD), genetic association studies are contradictory. We used 1008 probable AD patients from the UK and applied a Multiple Indicators Multiple Causes (MIMIC) approach to investigate the effect of 11 polymorphisms in the serotonergic and dopaminergic systems, on four behavioural sub-phenotypes, namely "psychosis"," moods", "agitation" and "behavioural dyscontrol", as well as on 12 NPI items. Significant findings included the association of DRD1 A48G with "psychosis" (p=0.037), the association of DAT1 VNTR with "agitation" (p=0.006) and the association of DRD4 with "moods" sub-phenotype (p=0.008). In addition, associations were identified between DRD1 A48G and DAT1 VNTR with aberrant motor behaviour (AMB) symptoms (p=0.001 and p=0.015 respectively), between DRD4 and sleep disturbances (p=0.018) and between 5HTTLPR and apathy (p=0.033). Finally, significant interactions were observed between COMT Val158Met and 5HTTLPR with "psychosis" (p=0.026), between HTTLPR and STin2 with "psychosis" (p=0.005), between DAT1 3'UTR VNTR and COMT Val158Met with "agitation" (p=0.0001) and between DAT1 3'UTR VNTR and 5HTTLPR with the "moods" factor (p=0.0027). The complexity of the interrelations between genetic variation, behavioural symptoms and clinical variables was efficiently captured by this MIMIC model. http://precedings.nature.com/documents/3896/version/1 Mon, 26 Oct 2009 17:32:00 UTC Genes of the serotonergic and dopaminergic pathways and their interaction affect the expression of Behavioural and Psychological Symptoms in Dementia (BPSD). hdl:10101/npre.2009.3896.1 2009-10-26 Petroula Proitsi Nature Precedings 2009-10-26T17:32:00Z Manuscript Genetics & Genomics Neuroscience http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/2304/version/2 The quantitative description of the motion of neurotransmitters in the synaptic cleft appears to be one of the most difficult problems in the modeling of synapses. Here we show in contradiction to the common view, that this process is merely governed by electric transport than diffusion forces. http://precedings.nature.com/documents/2304/version/2 Mon, 22 Jun 2009 10:19:39 UTC The Predominance of Electric Transport in Synaptic Transmission hdl:10101/npre.2009.2304.2 2009-06-22 Hamid Reza Noori Nature Precedings 2009-06-22T10:19:39Z Manuscript Neuroscience http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/2963/version/1 In this study we demonstrate for the first time that GSH could rapidly conjugate with dopamine (DA)-derived DA-o-quinones without enzymatic catalysis to form short-lived intermediate GSH-conjugates (2-S-GSH-DA-o-quinone and 5-S-GSH-DA-o-quinone). These intermediate GSH-conjugates are unstable and would finally form reactive or non-reactive GSH-conjugates dependent on ambient reductive forces. Under insufficient reductive forces, the intermediate GSH-conjugates could cyclize spontaneously to form reactive 7-S-GSH-aminochrome (7-S-GSH-AM). The 7-S-GSH-AM is so reactive that it could further react with another GSH to form 4,7-bi-GSH-5,6-dihydroindole. Its reactivity could also abrogate tyrosinase activity in solutions. In addition, the 7-S-GSH-AM could further undergo internal rearrangement to form non-reactive 7-S-GSH-5,6-dihydroindole. From these novel findings, we propose two detrimental positive feedback loops involving accelerated DA oxidation, increased GSH consumption and impaired GSH detoxification efficiency, as the underlying chemical explanation for dopaminergic neuron degeneration in Parkinson's disease. http://precedings.nature.com/documents/2963/version/1 Mon, 23 Mar 2009 10:16:43 UTC Glutathione (GSH) conjugates with dopamine (DA)-derived quinones to form reactive or non-reactive GSH-conjugates hdl:10101/npre.2009.2963.1 2009-03-23 Zhidong Zhou Nature Precedings 2009-03-23T10:16:43Z Manuscript Biotechnology Chemistry Neuroscience Pharmacology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/2304/version/1 The quantitative description of the motion of neurotransmitters in the synaptic cleft appears to be one of the most difficult problems in the modeling of synapses. Here we show in contradiction to the common view, that this process is merely governed by electric transport than diffusion forces. http://precedings.nature.com/documents/2304/version/1 Tue, 16 Sep 2008 00:38:17 UTC The Predominance of Electric Transport in Synaptic Transmission hdl:10101/npre.2008.2304.1 2008-09-16 Hamid Reza Noori Nature Precedings 2008-09-16T00:38:17Z Manuscript Neuroscience http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2006.9.1 Integration of neurotransmitter and neuromodulator signals in the striatum plays a central role in the functions and dysfunctions of the basal ganglia. DARPP-32 is a key actor of this integration in the GABAergic medium-size spiny neurons, in particular in response to dopamine and glutamate. When phosphorylated by cAMP-dependent protein kinase (PKA) DARPP-32 inhibits protein phosphatase-1 (PP1), whereas when phosphorylated by cyclin-dependent kinase 5 (CDK5) it inhibits PKA. DARPP-32 is also regulated by casein kinases and by several protein phosphatases. These complex and intricate regulations make simple predictions of DARPP-32 dynamic behaviour virtually impossible. We used detailed quantitative modelling of the regulation of DARPP-32 phosphorylation to improve our understanding of its function. The models included all the combinations of the three best characterized phosphorylation sites of DARPP-32, their regulation by kinases and phosphatases, and the regulation of those enzymes by cAMP and Ca2+ signals. Dynamic simulations allowed to observe the temporal relationships between cAMP and Ca2+ signals. We confirmed that the proposed regulation of protein phosphatase-2A (PP2A) by calcium can account for the observed decrease of Threonine 75 phosphorylation upon glutamate receptor activation. Sensitivity analysis showed that CDK5 activity is a major regulator of the response, as previously suggested. Conversely, the regulation of PP2A by PKA or by calcium, had little effect on the function of DARPP-32 in these conditions. The simulations showed that DARPP-32 is not only a robust signal integrator, but also a coincidence detector, the delay between cAMP and calcium signals affecting the response to the latter. This integration did not depend on the concentration of DARPP-32, while the absolute response on PP1 varied linearly. In silico mutants showed that Ser137 phosphorylation affects the coincidence detector function, and that constitutive phosphorylation in Ser137 transforms DARPP-32 in a quasi-irreversible switch. This work is a first attempt to better understand the complex interactions between cAMP and Ca2+ regulation of DARPP-32. Progressive inclusion of additional components should lead to a realistic model of signalling networks underlying the function of striatal neurons. http://dx.doi.org/10.1038/npre.2006.9.1 Thu, 30 Nov 2006 15:06:03 UTC DARPP-32 is a robust integrator of dopamine and glutamate signals doi:10.1038/npre.2006.9.1 2006-11-30 Nicolas Le Novere Nature Precedings 2006-11-30T15:06:03Z Poster Neuroscience http://creativecommons.org/licenses/by/2.5/