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Báo cáo y học: "Serotonin synthesis, release and reuptake in terminals: a mathematical model"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Serotonin synthesis, release and reuptake in terminals: a mathematical model. | Best et al. Theoretical Biology and Medical Modelling 2010 7 34 http www.tbiomed.eom content 7 1 34 THEORETICAL BIOLOGY AND MEDICAL MODELLING RESEARCH Open Access Serotonin synthesis release and reuptake in terminals a mathematical model Janet Best1 H Frederik Nijhout2 Michael Reed3 Correspondence jbest@math.ohio-state.edu department of Mathematics The Ohio State University Columbus OH 43210 USA Abstract Background Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation social hierarchies aggression and suicidality obsessive compulsive disorder alcoholism anxiety and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics neurochemistry electrophysiology and behavior. Though associations have been found between functions at these different levels in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system. Methods We construct a mathematical model of serotonin synthesis release and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors the transport of tryptophan into the terminal and the metabolism of serotonin as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data. Results We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct in silico experiments on the clearance of extracellular serotonin normally and in the presence of fluoxetine and compare to experimental data. We study the effects of various .