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Dopamine Turnover (dopamine + turnover)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Heritability, correlations and in silico mapping of locomotor behavior and neurochemistry in inbred strains of mice

GENES, BRAIN AND BEHAVIOR, Issue 4 2005
T. R. Mhyre
The midbrain dopamine system mediates normal and pathologic behaviors related to motor activity, attention, motivation/reward and cognition. These are complex, quantitative traits whose variation among individuals is modulated by genetic, epigenetic and environmental factors. Conventional genetic methods have identified several genes important to this system, but the majority of factors contributing to the variation remain unknown. To understand these genetic and environmental factors, we initiated a study measuring 21 behavioral and neurochemical traits in 15 common inbred mouse strains. We report trait data, heritabilities and genetic and non-genetic correlations between pheno-types. In general, the behavioral traits were more heritable than neurochemical traits, and both genetic and non-genetic correlations within these trait sets were high. Surprisingly, there were few significant correlations between the behavioral and the individual neurochemical traits. However, striatal serotonin and one measure of dopamine turnover (DOPAC/DA) were highly correlated with most behavioral measures. The variable accounting for the most variation in behavior was mouse strain and not a specific neurochemical measure, suggesting that additional genetic factors remain to be determined to account for these behavioral differences. We also report the prospective use of the in silico method of quantitative trait loci (QTL) analysis and demonstrate difficulties in the use of this method, which failed to detect significant QTLs for the majority of these traits. These data serve as a framework for further studies of correlations between different midbrain dopamine traits and as a guide for experimental cross designs to identify QTLs and genes that contribute to these traits. [source]

Aggressive behavior, related conduct problems, and variation in genes affecting dopamine turnover

AGGRESSIVE BEHAVIOR, Issue 3 2010
Elena L. Grigorenko
Abstract A number of dopamine-related genes have been implicated in the etiology of violent behavior and conduct problems. Of these genes, the ones that code for the enzymes that influence the turnover of dopamine (DA) have received the most attention. In this study, we investigated 12 genetic polymorphisms in four genes involved with DA functioning (COMT, MAOA and MAOB, and D,H) in 179 incarcerated male Russian adolescents and two groups of matched controls: boys without criminal records referred to by their teachers as (a) "troubled-behavior-free" boys, n=182; and (b) "troubled-behavior" boys, n=60. The participants were classified as (1) being incarcerated or not, (2) having the DSM-IV diagnosis of conduct disorder (CD) or not, and (3) having committed violent or nonviolent crimes (for the incarcerated individuals only). The findings indicate that, although no single genetic variant in any of the four genes differentiated individuals in the investigated groups, various linear combinations (i.e., haplotypes) and nonlinear combinations (i.e., interactions between variants within and across genes) of genetic variants resulted in informative and robust classifications for two of the three groupings. These combinations of genetic variants differentiated individuals in incarceration vs. nonincarcerated and CD vs. no-CD groups; no informative combinations were established consistently for the grouping by crime within the incarcerated individuals. This study underscores the importance of considering multiple rather than single markers within candidate genes and their additive and interactive combinations, both with themselves and with nongenetic indicators, while attempting to understand the genetic background of such complex behaviors as serious conduct problems. Aggr. Behav. 36:158,176, 2010. © 2010 Wiley-Liss, Inc. [source]

Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa-induced motor complications

MOVEMENT DISORDERS, Issue 3 2003
Frédéric Calon PhD
Abstract Brain samples from 14 Parkinson's disease patients, 10 of whom developed motor complications (dyskinesias and/or wearing-off) on dopaminomimetic therapy, and 11 controls were analyzed. Striatal 3,-(4- 125I-iodophenyl)tropane-2,-carboxylic acid isopropyl ester ([125I]RTI-121) -specific binding to dopamine transporter and concentration of dopamine were markedly decreased, but no association between level of denervation and development of motor complications was observed. The homovanillic acid/dopamine ratio of concentrations was higher in putamen of patients with wearing-off compared to those without. Striatal 35S-labeled t-butylbicyclophosphorothionate ([35S]TBPS) and [3H]flunitrazepam binding to GABAA receptors were unchanged in patients with Parkinson's disease, whereas [125I]CGP 64213 -specific binding to GABAB receptors was decreased in the putamen and external segment of the globus pallidus of parkinsonian patients compared with controls. [3H]Flunitrazepam binding was increased in the putamen of patients with wearing-off compared to those without. [35S]TBPS,specific binding was increased in the ventral internal globus pallidus of dyskinetic subjects. These data suggest altered dopamine metabolism and increased GABAA receptors in the putamen related to the pathophysiology of wearing-off. The present results also suggest that an up-regulation of GABAA receptors in the internal globus pallidus is linked to the pathogenesis of levodopa-induced dyskinesias. © 2002 Movement Disorder Society [source]

Dopamine D2 receptor knockout mice develop features of Parkinson disease,

ANNALS OF NEUROLOGY, Issue 4 2009
Rogan B. Tinsley PhD
Objective This study questions whether increased dopamine (DA) turnover in nigral neurons leads to formation of Lewy bodies (LBs), the characteristic ,-synuclein,containing cytoplasmic inclusion of Parkinson disease (PD). Methods Mice with targeted deletion of the dopamine D2 receptor gene (D2R[,/,]) have higher striatal and nigral dopamine turnover and elevated oxidative stress. These mice were examined for evidence of histological, biochemical, and gene expression changes consistent with a synucleinopathy. Results LB-like cytoplasmic inclusions containing ,-synuclein and ubiquitin were present in substantia nigra pars compacta (SNpc) neurons of older D2R(,/,) mice, and were also occasionally seen in aged wild-type mice. These inclusions displaced the nucleus of affected cells and were eosinophilic. Diffuse cytosolic ,-synuclein immunoreactivity in SNpc neurons increased with age in both wild-type and D2R(,/,) mice, most likely because of redistribution of ,-synuclein from striatal terminals to SNpc cell bodies. Gene and protein expression studies indicated endoplasmic reticulum (ER) stress and changes in trafficking and autophagic pathways in D2R(,/,) SNpc. These changes were accompanied by a loss of DA terminals in the dorsal striatum, although there was no evidence of progressive cell death in the SNpc. Interpretation Increased sprouting and DA turnover, as observed in PD and D2R(,/,) mice, augments LB-like inclusions and axonal degeneration of dopaminergic neurons. These changes are associated with ER stress and autophagy. Ann Neurol 2009;66:472,484 [source]