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Dopaminergic Modulation (dopaminergic + modulation)
Selected AbstractsSubstantial Thalamostriatal Dopaminergic Defect in Unverricht-Lundborg DiseaseEPILEPSIA, Issue 9 2007Miikka Korja Summary:,Purpose: Unverricht-Lundborg disease (ULD) is currently classified as progressive myoclonus epilepsy. Myoclonus, the characteristic symptom in ULD, suggests that dopamine neurotransmission may be involved in the pathophysiology of ULD. Our purpose was to examine brain dopaminergic function in ULD patients. Methods: Four genetically and clinically diagnosed ULD patients and eight healthy controls were scanned with [11C]raclopride-PET. PET images were coregistered to individual 1.5T MR images and region-of-interest analysis was performed for the striatum and thalamus. Standardized uptake values and individual voxel-wise binding potential maps of the patients and controls were also analyzed. Results: ULD patients had markedly higher (31,54%) dopamine D2-like receptor availabilities than healthy controls in both the striatum and the thalamus. The proportionally highest binding potentials were detected in the thalamus. There were no significant differences in the cerebellar uptake of [11C]raclopride in ULD patients versus healthy controls. Voxel-based results were in accordance with the region-of-interest analysis. Conclusions: These results suggest that dopaminergic modulation at the level of the striatum and thalamus could be a crucial factor contributing to the symptoms of ULD. In the light of our data, we propose that ULD with dopamine dysfunction and dyskinetic symptoms shares certain pathophysiological mechanisms with classical movement disorders. Future studies are therefore warranted to study the effect of dopaminergic pharmacotherapy in ULD. [source] GABAergic mechanism mediated via D1 receptors in the rat periaqueductal gray participates in the micturition reflex: an in vivo microdialysis studyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008Takeya Kitta Abstract The periaqueductal gray (PAG) is critically involved in the micturition reflex, but little is known about the neuronal mechanisms involved. The present study elucidated dynamic changes in dopamine (DA), glutamate and ,-aminobutyric acid (GABA) in the rat PAG during the micturition reflex, with a focus on dopaminergic modulation using in vivo microdialysis combined with cystometrography. Extracellular levels of DA and glutamate increased, whereas levels of GABA decreased, in parallel with the micturition reflex. Application of a D1 receptor antagonist into the PAG produced increases in maximal voiding pressure (MVP) and decreases in intercontraction interval (ICI), suggesting that the micturition reflex was facilitated by D1 receptor blockade. The D1 receptor antagonist prevented micturition-induced decreases in GABA efflux but had no effect on DA or glutamate. Neither a D2 receptor antagonist nor a D1/D2 receptor agonist affected these neurochemical and physiological parameters. Micturition-induced inhibition of GABA was not observed in 6-hydroxydopamine (6-OHDA)-lesioned rats, an animal model of Parkinson's disease. 6-OHDA-lesioned rats exhibited bladder hyperactivity evaluated by increases in MVP and decreases in ICI, mimicking facilitation of the micturition reflex induced by D1 receptor blockade. These findings suggest that the micturition reflex is under tonic dopaminergic regulation through D1 receptors, in which a GABAergic mechanism is involved. Bladder hyperactivity observed in 6-OHDA-lesioned rats may be caused by dysfunction of GABAergic regulation underlying the micturition reflex. The present findings contribute to our understanding not only of the neurophysiology of the micturition reflex but also of the pathophysiology of lower urinary tract dysfunction in patients with Parkinson's disease. [source] Modulation of perch connexin35 hemi-channels by cyclic AMP requires a protein kinase A phosphorylation siteJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003Georgia Mitropoulou Abstract Retinal neurons are coupled via gap junctions, which function as electrical synapses that are gated by ambient light conditions. Gap junctions connecting either horizontal cells or AII amacrine cells are inhibited by the neurotransmitter dopamine, via the activation of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway. Fish connexin35 (Cx35) and its mouse ortholog, Cx36, are good candidates to undergo dopaminergic modulation, because they have been detected in the inner plexiform layer of the retina, where Type II amacrine cells establish synaptic contacts. We have taken advantage of the ability of certain connexins to form functional connexons (hemi-channels), when expressed in Xenopus oocytes, to investigate whether pharmacological elevation of cAMP modulates voltage-activated hemi-channel currents in single oocytes. Injection of perch Cx35 RNA into Xenopus oocytes induced outward voltage-dependent currents that were recorded at positive membrane potentials. Incubation of oocytes with 8-bromoadenosine 3,,5,-cyclic monophosphate (8-Br-cAMP), a membrane permeable cAMP analog, resulted in a dose-dependent and reversible inhibition of hemi-channel currents at the more positive voltage steps. In contrast, treatment with 8-Br-cAMP did not have any effect on hemi-channel currents induced by skate Cx35. Amino acid sequence comparison of the two fish connexins revealed, in the middle cytoplasmic loop of perch Cx35, the presence of a PKA consensus sequence that was absent in the skate connexin. The results obtained with two constructs in which the putative PKA phosphorylation site was either suppressed (perch Cx35R108Q) or introduced (skate Cx35Q108R) indicate that it is responsible for the inhibition of hemi-channel currents. These studies demonstrate that perch Cx35 is a target of the cAMP/PKA signaling pathway and identify a consensus PKA phosphorylation site that is required for channel gating. © 2003 Wiley-Liss, Inc. [source] Brain dopaminergic modulation associated with executive function in Parkinson's disease,MOVEMENT DISORDERS, Issue 13 2009Karim Farid MD Abstract The progressive development of deficits in executive functions, including action planning, is a well-known complication of Parkinson's disease. A dysfunction of the prefrontal lobe, which is known to be involved in the control of inhibitory processes, could explain the difficulties in initiating behavior or inhibiting ongoing actions in patients with PD. The strong dopaminergic innervation of the prefrontal cortex raises questions about the putative effects of dopa therapy on this cognitive impairment. In the present study, we used fMRI to examine the functional influence of dopa therapy on neural activity during a go/no-go task in nine patients with and without levodopa treatment and in matched controls. Whereas the patient and control subjects exhibited the same performance during the go/no-go task, different patterns of brain activation were observed depending on the dopaminergic status. The drug-off state was characterized by more widely distributed brain activity, mainly in the bilateral caudate. Levodopa did not fully restore normal brain activation and induced changes in the pattern of cingulate cortex activity, which was more pronounced in the rostral part in the drug-off state and in the caudal part after levodopa intake. These results support the idea of a critical role for dopamine in the control of executive functions in patients with PD. © 2009 Movement Disorder Society [source] The effect of ,two hit' neonatal and young-adult stress on dopaminergic modulation of prepulse inhibition and dopamine receptor densityBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2009Kwok Ho Christopher Choy Background and purpose:, A combination of early neurodevelopmental insult(s) and young-adult stress exposure may be involved in the development of schizophrenia. We studied prepulse inhibition (PPI) regulation in rats after an early stress, maternal deprivation, combined with a later stress, simulated by chronic corticosterone treatment, and also determined whether changes in brain dopamine receptor density were involved. Experimental approach:, Rats were subjected to either 24 h maternal deprivation on postnatal day 9, corticosterone treatment from 8 to 10 weeks of age, or both. At 12 weeks of age, the rats were injected with 0.1, 0.3 or 1.0 mg·kg,1 of apomorphine or 0.5 or 2.5 mg·kg,1 of amphetamine and PPI was determined using automated startle boxes. Dopamine D1 and D2 receptor levels were assessed in the nucleus accumbens and caudate nucleus using receptor autoradiography. Key results:, Young-adult treatment with corticosterone resulted in attenuated disruption of PPI by apomorphine and amphetamine. In some rats, maternal deprivation resulted in reduced baseline PPI which added to the effect of corticosterone treatment. There was no down-regulation of dopamine D1 or D2 receptors. Conclusions and implications:, These results confirm and extend our finding of an inhibitory interaction of developmental stress on dopaminergic regulation of PPI. No corresponding changes in dopamine receptor density were observed in brain regions with a major involvement in PPI regulation, suggesting long-lasting desensitization of dopamine receptor signalling or indirect changes in PPI regulation. [source] | |||||||||||||