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https://www.readbyqxmd.com/read/27883923/gilles-de-la-tourette-syndrome-is-associated-with-hypermethylation-of-the-dopamine-d2-receptor-gene
#1
Kirsten R Müller-Vahl, Gesa Loeber, Alexandra Kotsiari, Linda Müller-Engling, Helge Frieling
Several lines of evidence support a "dopaminergic hypothesis" in the pathophysiology of Gilles de la Tourette syndrome (TS). The aim of this study was to investigate for the first time epigenetic changes in DNA methylation in different dopamine genes in adult patients with TS. We included 51 well characterized adult patients with TS (41 males, 10 females, mean age = 35 ± 12.6 years, range, 18-71 years) and compared results with data from a group of 51 sex- and age-matched healthy controls. Bisulfite sequencing was used to measure peripheral DNA methylation of the dopamine transporter (DAT), the dopamine D2 receptor (DRD2), and the catechol-O-methyltransferase (COMT) genes...
November 12, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27458023/manic-symptom-severity-correlates-with-comt-activity-in-the-striatum-a-post-mortem-study
#2
Marco Bortolato, Consuelo Walss-Bass, Peter M Thompson, Jackob Moskovitz
OBJECTIVES: The enzyme catechol-O-methyltransferase (COMT), which catalyses the degradation of dopamine and norepinephrine, is posited to participate in the pathophysiology of bipolar disorder (BD) and schizophrenia. In support of this notion, rich evidence has documented that the severity of various BD and schizophrenia symptoms is moderated by rs4680, a single nucleotide polymorphism of the COMT gene featuring a valine (Val)-to-methionine (Met) substitution that results in lower catalytic activity...
July 26, 2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/27445153/subsecond-regulation-of-synaptically-released-dopamine-by-comt-in-the-olfactory-bulb
#3
Renee Cockerham, Shaolin Liu, Roger Cachope, Emi Kiyokage, Joseph F Cheer, Michael T Shipley, Adam C Puche
UNLABELLED: The efficacy of neurotransmission depends on multiple factors, including presynaptic vesicular release of transmitter, postsynaptic receptor populations and clearance/inactivation of the transmitter. In the olfactory bulb (OB), short axon cells (SACs) form an interglomerular circuit that uses GABA and dopamine (DA) as cotransmitters. Selective optical activation of SACs causes GABA and DA co-release, resulting in a fast, postsynaptic GABA inhibitory response and a slower G-protein-coupled DA rebound excitation...
July 20, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27429661/neural-correlates-of-reward-processing-in-adults-with-22q11-deletion-syndrome
#4
Esther D A van Duin, Liesbet Goossens, Dennis Hernaus, Fabiana da Silva Alves, Nicole Schmitz, Koen Schruers, Therese van Amelsvoort
BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission...
2016: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/27226189/elimination-of-extracellular-dopamine-in-the-medial-prefrontal-cortex-of-conscious-mice-analysed-using-selective-enzyme-and-uptake-inhibitors
#5
A Tammimaki, A Aonurm-Helm, M Kaenmaki, P T Mannisto
We have shown in a previous study that in the medial prefrontal cortex (mPFC) of Comt knockout animals, uptake1 followed by oxidation accounts for approximately 50% and uptake2 followed by O-methylation for the remaining 50% of dopamine clearance. However, compensatory mechanisms in genetically modified animals may have affected the result. Therefore, in the present study, we gave a high dose (30 mg/kg) of tolcapone in combination with pargyline and reboxetine to C57BL/6J mice to see whether the earlier findings could be confirmed...
April 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/27028825/-changes-in-the-expression-of-dopaminergic-genes-in-brain-structures-of-male-mice-exposed-to-chronic-social-defeat-stress-an-rna-seq-study
#6
I L Kovalenko, D A Smagin, A G Galyamina, Yu L Orlov, N N Kudryavtseva
Whole-transcriptome analysis (RNA-seq) has been used to analyze changes in the expression of dopaminergic genes that encode proteins involved in the synthesis, inactivation, and neurotransmission of dopamine in the striatum, ventral tegmental area, raphe nuclei of the midbrain, hypothalamus, and hippocampus of male mice subjected to chronic social defeat. The expression of Th, Ddc, and Slc6A3 (Dat1) was upregulated, while that of Ppp1r1b and Sncg was downregulated in the ventral tegmental area; the expression of Th, Ddc, Drd2, and Sncg was downregulated in the raphe nuclei of midbrain; the expression of Th, Aldh2, and Ppp1r1b was upregulated, while that of Маоа was downregulated in the hypothalamus; Drd1 and Snca expression was downregulated and that of Sncb was upregulated in the striatum, and Sncb expression was upregulated in the hippocampus...
January 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/26818509/variability-in-dopamine-genes-dissociates-model-based-and-model-free-reinforcement-learning
#7
Bradley B Doll, Kevin G Bath, Nathaniel D Daw, Michael J Frank
UNLABELLED: Considerable evidence suggests that multiple learning systems can drive behavior. Choice can proceed reflexively from previous actions and their associated outcomes, as captured by "model-free" learning algorithms, or flexibly from prospective consideration of outcomes that might occur, as captured by "model-based" learning algorithms. However, differential contributions of dopamine to these systems are poorly understood. Dopamine is widely thought to support model-free learning by modulating plasticity in striatum...
January 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26622527/dynamic-changes-of-five-neurotransmitters-and-their-related-enzymes-in-various-rat-tissues-following-%C3%AE-asarone-and-levodopa-co-administration
#8
Liping Huang, Minzhen Deng, Yongqi Fang, Ling Li
The aim of the present study was to investigate the dynamic changes of five neurotransmitters and their associated enzymes in the rat plasma and brain tissues following the co-administration of β-asarone and levodopa (L-dopa). The rats were divided into five groups, including the control group and four treatment groups that were intragastrically co-administered β-asarone and L-dopa and sacrificed at 1, 5, 18 and 48 h, respectively. Neurotransmitter levels in the brain tissues and plasma were detected using high performance liquid chromatograph and the related enzymes of dopamine (DA) were measured using an enzyme-linked immunosorbent assay...
October 2015: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/26474929/sport-physiology-dopamine-and-nitric-oxide-some-speculations-and-hypothesis-generation
#9
J G Landers, Tobias Esch
Elite Spanish professional soccer players surprisingly showed a preponderance of an allele coding for nitric oxide synthase (NOS) that resulted in lower nitric oxide (NO) compared with Spanish endurance and power athletes and sedentary men. The present paper attempts a speculative explanation. Soccer is an "externally-paced" (EP) sport and team work dependent, requiring "executive function skills". We accept that time interval estimation skill is, in part, also an executive skill. Dopamine (DA) is prominent among the neurotransmitters with a role in such skills...
December 2015: Medical Hypotheses
https://www.readbyqxmd.com/read/26277034/mesocorticolimbic-dopamine-functioning-in-primary-psychopathy-%C3%A2-a-source-of-within-group-heterogeneity
#10
REVIEW
Bariş O Yildirim, Jan J L Derksen
Despite similar emotional deficiencies, primary psychopathic individuals can be situated on a continuum that spans from controlled to disinhibited. The constructs on which primary psychopaths are found to diverge, such as self-control, cognitive flexibility, and executive functioning, are crucially regulated by dopamine (DA). As such, the goal of this review is to examine which specific alterations in the meso-cortico-limbic DA system and corresponding genes (e.g., TH, DAT, COMT, DRD2, DRD4) might bias development towards a more controlled or disinhibited expression of primary psychopathy...
October 30, 2015: Psychiatry Research
https://www.readbyqxmd.com/read/25963102/genotype-status-of-the-dopamine-related-catechol-o-methyltransferase-comt-gene-corresponds-with-desirability-of-unhealthy-foods
#11
Deanna L Wallace, Esther Aarts, Federico d'Oleire Uquillas, Linh C Dang, Stephanie M Greer, William J Jagust, Mark D'Esposito
The role of dopamine is extensively documented in weight regulation and food intake in both animal models and humans. Yet the role of dopamine has not been well studied in individual differences for food desirability. Genotype status of the dopamine-related catechol-O-methyltransferase (COMT) gene has been shown to influence dopamine levels, with greater COMT enzymatic activity in val/val individuals corresponding to greater degradation of dopamine. Decreased dopamine has been associated with poorer cognitive control and diminished goal-directed behavior in various behavioral paradigms...
September 2015: Appetite
https://www.readbyqxmd.com/read/25896799/epistatic-interaction-of-bdnf-and-comt-on-the-frontostriatal-system
#12
C Wang, B Liu, H Long, L Fan, J Li, X Zhang, C Qiu, C Yu, T Jiang
The frontostriatal system plays a critical role in emotional and cognitive control. Brain-derived neurotrophic factor (BDNF) influences the release of dopamine (DA) in the ventral striatum (VST), while catechol-O-methyltransferase (COMT) impacts DA availability in the prefrontal cortex (PFC). Behavioral studies have already shown a genetic interaction of BDNF Val66Met and COMT Val158Met, but the interaction on the DA-related neural circuit has not been previously studied. Here we show, using functional magnetic resonance imaging in a sample of healthy human subjects, that BDNF and COMT epistatically interacted on the functional connectivity between the bilateral VST and the anterior cingulate cortex...
July 9, 2015: Neuroscience
https://www.readbyqxmd.com/read/25753458/dopaminergic-denervation-severity-depends-on-comt-val158met-polymorphism-in-parkinson-s-disease
#13
RANDOMIZED CONTROLLED TRIAL
Julia Muellner, Iman Gharrad, Marie-Odile Habert, Aurélie Kas, Jean-Baptiste Martini, Florence Cormier-Dequaire, Khadija Tahiri, Marie Vidailhet, Niklaus Meier, Alexis Brice, Michael Schuepbach, Alain Mallet, Andreas Hartmann, Jean-Christophe Corvol
BACKGROUND: Catecholamine-O-methyl-tranferase (COMT) initiates dopamine degradation. Its activity is mainly determined by a single nucleotide polymorphism in the COMT gene (Val158Met, rs4680) separating high (Val/Val, COMT(HH)), intermediate (Val/Met, COMT(HL)) and low metabolizers (Met/Met, COMT(LL)). We investigated dopaminergic denervation in the striatum in PD patients according to COMT rs4680 genotype. METHODS: Patients with idiopathic PD were assessed for motor severity (UPDRS-III rating scale in OFF-state), dopaminergic denervation using [123I]-FP-CIT SPECT imaging, and genotyped for the COMT rs4680 enzyme...
May 2015: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/25596589/dopaminergic-modulation-of-cognitive-preparation-for-overt-reading-evidence-from-the-study-of-genetic-polymorphisms
#14
Christiane Arnold, Suzana Gispert, Halvard Bonig, Frederic von Wegner, Sriramya Somasundaram, Christian A Kell
Choosing and implementing the rules for contextually adequate behavior depends on frontostriatal interactions. Observations in Parkinson's disease and pharmacological manipulations of dopamine transmission suggest that these corticobasal loops are modulated by dopamine. To determine, therefore, the physiological contributions of dopamine to task-rule-related processing, we performed a cue-target fMRI reading paradigm in 71 healthy participants and investigated the effects of COMT Val158Met, DAT1 VNTR 9/10, and DRD2/ANKK1 polymorphisms...
April 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/24979760/dissociable-contribution-of-prefrontal-and-striatal-dopaminergic-genes-to-learning-in-economic-games
#15
Eric Set, Ignacio Saez, Lusha Zhu, Daniel E Houser, Noah Myung, Songfa Zhong, Richard P Ebstein, Soo Hong Chew, Ming Hsu
Game theory describes strategic interactions where success of players' actions depends on those of coplayers. In humans, substantial progress has been made at the neural level in characterizing the dopaminergic and frontostriatal mechanisms mediating such behavior. Here we combined computational modeling of strategic learning with a pathway approach to characterize association of strategic behavior with variations in the dopamine pathway. Specifically, using gene-set analysis, we systematically examined contribution of different dopamine genes to variation in a multistrategy competitive game captured by (i) the degree players anticipate and respond to actions of others (belief learning) and (ii) the speed with which such adaptations take place (learning rate)...
July 1, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/24910244/coadministration-of-%C3%AE-asarone-and-levodopa-increases-dopamine-in-rat-brain-by-accelerating-transformation-of-levodopa-a-different-mechanism-from-madopar
#16
Liping Huang, Minzhen Deng, Sheng Zhang, Yongqi Fang, Ling Li
The aim of the present study was to investigate the effect of coadministration of β-asarone and levodopa (l-dopa) on increasing dopamine (DA) in the striatum of healthy rats. Rats were randomly divided into four groups: (i) a normal group, administered normal saline; (ii) a Madopar group, administered 75 mg/kg Madopar (l-dopa : benserazide, 4 : 1); (iii) an l-dopa group, administered 60 mg/kg l-dopa; and (iv) a group coadministered 15 mg/kg β-asarone and 60 mg/kg l-dopa. All drugs (or normal saline) were administered intragastrically twice a day for 7 days...
September 2014: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/24880075/effects-of-acute-and-sub-chronic-l-dopa-therapy-on-striatal-l-dopa-methylation-and-dopamine-oxidation-in-an-mptp-mouse-model-of-parkinsons-disease
#17
COMPARATIVE STUDY
Marquitta L Smith, Jennifer King, Lemuel Dent, Veronica Mackey, Gladson Muthian, Brenya Griffin, Clivel G Charlton
AIMS: The molecular mechanisms for the loss of 3,4-dihydroxyphenylalanine (l-dopa) efficacy during the treatment of Parkinson's disease (PD) are unknown. Modifications related to catecholamine metabolism such as changes in l-dopa and dopamine (DA) metabolism, the modulation of catecholamine enzymes and the production of interfering metabolites are the primary concerns of this study. MAIN METHODS: Normal (saline) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) pre-treated mice were primed with 100mg/kg of l-dopa twice a day for 14 days, and a matching group remained l-dopa naïve...
August 6, 2014: Life Sciences
https://www.readbyqxmd.com/read/24863964/age-dependent-dopaminergic-dysfunction-following-fetal-exposure-to-atrazine-in-sd-rats
#18
Yanshu Li, Yan Sun, Junwei Yang, Yanping Wu, Jia Yu, Baixiang Li
The herbicide, atrazine (ATR), is used worldwide and its contamination in the environment has resulted in documented human exposure. It has also been shown that ATR results in dopaminergic neurotoxicity, however, few studies have investigated the long-term effects of ATR following in utero exposure. Therefore, we evaluated the effects of ATR exposure in Sprague Dawley rats during gestational on the offspring dopaminergic system development. Pregnant dams were treated with oral ATR at 0, 25, 50 mg/kg/day from gestational day 0 to postnatal day 1...
May 2014: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/24842650/1-benzyl-1-2-3-4-tetrahydroisoquinoline-an-endogenous-neurotoxic-compound-disturbs-the-behavioral-and-biochemical-effects-of-l-dopa-in-vivo-and-ex-vivo-studies-in-the-rat
#19
Agnieszka Wąsik, Irena Romańska, Jerzy Michaluk, Małgorzata Kajta, Lucyna Antkiewicz-Michaluk
Environmental factors and endogenously produced toxins, such as 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), are considered to be involved in the pathogenesis of Parkinson's disease (PD). In this study, we investigated the impact of single and multiple 1BnTIQ (25 and 50 mg/kg i.p.) administration on L-DOPA-induced changes in the rate of dopamine and serotonin metabolism in the rat brain. Additionally, using in vivo microdialysis, we measured the impact of acute and multiple 1BnTIQ administrations on L-DOPA-induced dopamine release in the striatum...
October 2014: Neurotoxicity Research
https://www.readbyqxmd.com/read/24639487/genetic-variation-in-comt-activity-impacts-learning-and-dopamine-release-capacity-in-the-striatum
#20
Eleanor H Simpson, Julia Morud, Vanessa Winiger, Dominik Biezonski, Judy P Zhu, Mary Elizabeth Bach, Gael Malleret, H Jonathan Polan, Scott Ng-Evans, Paul E M Phillips, Christoph Kellendonk, Eric R Kandel
A common genetic polymorphism that results in increased activity of the dopamine regulating enzyme COMT (the COMT Val(158) allele) has been found to associate with poorer cognitive performance and increased susceptibility to develop psychiatric disorders. It is generally assumed that this increase in COMT activity influences cognitive function and psychiatric disease risk by increasing dopamine turnover in cortical synapses, though this cannot be directly measured in humans. Here we explore a novel transgenic mouse model of increased COMT activity, equivalent to the relative increase in activity observed with the human COMT Val(158) allele...
April 2014: Learning & Memory
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