Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Signs of attentional dysfunction mimicking spatial neglect have been described both in humans with lateralised Parkinson's Disease (PD) and in animals with MPTP-related hemiparkinsonism. Such deficits have been attributed to dopamine loss in basal ganglia and cortical targets. However, in previous studies the existence of neglect was assumed from behavioural tests which needed a motor output, thus entailing interpretation ambiguities due to effects of directional hypokinesia. We recorded brain event-related potentials (ERPs) evoked by the presentation of target somatic stimuli to the affected and non-affected sides in 44 patients with unilateral or asymmetrical PD. The N2 and P3 ERP components were specifically analysed, since (a) they are triggered selectively by task-relevant, attended sensory stimuli; (b) their latency reflects stimulus evaluation time, independently from the execution of a motor response, and (c) they have proved to be abnormal in hemineglect syndromes due to focal brain lesions. Irrespective of the side (left or right) of motor symptom predominance there were no significant ERP differences to stimulation of the affected and non-affected limbs, nor was there any correlation between ERP latencies and the degree of dopamine-related motor impairment. The P3 latency was abnormally delayed in 23% of the patients, but there was no trend for abnormalities to concentrate on the affected side. This study does not confirm the existence of a significant attentional impairment toward the affected limb in lateralised PD, and suggests that previous clinical evidence of "neglect' behaviour in PD might be linked to directional hypokinesia, thus reflecting intentional, rather than attentional lateralised deficits.
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PMID:Brain responses to detection of right or left somatic targets are symmetrical in unilateral Parkinson's disease: a case against the concept of "parkinsonian neglect'. 895 46

The effects upon the trajectories of practised slow (approximately 9 degrees/s) voluntary wrist-extension movements of applying vibration to the tendon of an antagonist muscle (flexor carpi radialis) during the course of the movement have been studied in patients with idiopathic Parkinson's disease and age-matched healthy individuals. In both patient and control groups, flexor vibration elicited undershooting of wrist-extension movements. Wrist extensor and flexor surface EMG recordings indicated that, in patients and controls, such undershooting resulted principally from sustained reductions in extensor (prime mover) activity. Small vibration reflexes were commonly elicited in the wrist flexors which, in both Parkinson's disease and healthy subjects, were usually otherwise virtually quiescent during these slow extension movements. The amplitudes of such vibration reflexes did not differ systematically between patient and control groups and appeared inadequate to have exerted an appreciable braking action upon the extension trajectories. However, the extent of vibration-induced undershooting was, on average, significantly less in the Parkinson's disease group. In a subgroup of patients with asymmetrical parkinsonism the effects of antagonist vibration upon wrist movements of the more and less affected limb were compared. The degree of vibration-induced undershooting was significantly smaller on the more affected side. This finding suggests that disturbed proprioceptive guidance of voluntary movements in Parkinson's disease is related to the severity of clinical motor deficits. A small number Parkinson's disease patients were studied 'ON' and 'OFF' their routine anti-parkinsonian medication. A non-significant tendency was found for vibration-induced errors to be less marked in the 'OFF' state. In a separate series of experiments, under isometric conditions, vibration-induced EMG changes were recorded whilst subjects attempted to maintain a steady (15% maximum) voluntary wrist extensor effort. Results in control subjects suggested that prolonged flexor vibration produced significant tonic reflex reciprocal inhibition of the extensor muscles. However, the strength of reflex inhibition appeared sufficient to account for only a small fraction of the undershooting observed during the movement tasks. Thus, our results are consistent with the existence of an abnormality of higher-level proprioceptive integration in Parkinson's disease in which there is a mismatch of sensory (proprioceptive) and motor (corollary discharge) information.
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PMID:Proprioceptive control of wrist movements in Parkinson's disease. Reduced muscle vibration-induced errors. 921 82

Single unit activity of substantia nigra pars reticulata (SNR) neurons was recorded bilaterally in rats subjected to unilateral 6-hydroxydopamine lesions of the ascending mesostriatal dopaminergic pathway, resulting in an almost complete loss of dopaminergic neurons in the ipsilateral SN pars compacta. Firing rate and firing pattern of SNR neurons in lesioned rats were compared with respective data from sham-lesioned rats and naive controls. In lesioned rats, the mean firing rate of SNR neurons at the lesioned side was significantly reduced and there was an increase in the occurrence of bursting activity. In contrast, firing rate in the contralateral SNR was significantly increased without change in the frequency of bursting neurons. This asymmetrical change in spontaneous firing characteristics of SNR neurons following the lesion could be involved in the complex behavioral changes seen in this model of Parkinson's disease.
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PMID:Hemispheric asymmetries in spontaneous firing characteristics of substantia nigra pars reticulata neurons following a unilateral 6-hydroxydopamine lesion of the rat nigrostriatal pathway. 925 38

Recently, we demonstrated amelioration of behavioral deficits associated with 6-hydroxydopamine-induced hemiparkinsonism by transplanting rat testis-derived Sertoli cells into adult male rat brains. In the present study, we used adult female hemiparkinsonian rats to investigate whether the beneficial effects of transplantation of Sertoli cells may be differentially affected by gender of the animal transplant recipient. At 1 month posttransplantation, animals transplanted with Sertoli cells showed functional recovery as revealed by significant reductions in apomorphine-induced rotational behavior and asymmetrical elevated body swing behavior. Control animals that received medium alone did not display any visible behavioral recovery. These results suggest that transplantation of Sertoli cells is not male hormone-dependent and further support the use of these cells as a graft source for Parkinson's disease and other neurological disorders.
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PMID:Intracerebral transplantation of testis-derived sertoli cells promotes functional recovery in female rats with 6-hydroxydopamine-induced hemiparkinsonism. 939 81

Parkinson's disease patients and control subjects performed a simultaneous bilateral reach-to-grasp task to two different sized objects and then pulled the two objects apart. The first phase of the task (reaching-to-grasp) allowed us to examine the issue that impairments in simultaneous movements for Parkinson's disease patients are seen in some tasks but not in others. It is suggested that the reason for this selective impairment is that Parkinson's disease compromises the ability to control multiple task-level degrees of freedom independently and concurrently (task-level degrees of freedom are defined as the number of independent parameters that require specification to perform the task). The first phase was used to test the hypothesis that Parkinson's disease results in a reduction of degrees of freedom that are independently controlled. It was predicted that Parkinson's disease patients would produce similar (homologous) movements of the two limbs (a symmetrical pattern) if the target objects have different accuracy requirements when they reach bilaterally to the two objects. For bilateral reaches for two different-size objects, only the control group showed reliably different patterns in the two limbs (asymmetrical pattern), while the Parkinson's disease group displayed a symmetrical pattern. These results provide support for the hypothesis that Parkinson's disease patients have a reduced capability to control multiple task-level degrees of freedom. The second phase of the task, which involved a transition from position control (reaching-to-grasp) to force control (stabilizing and pulling) was used to examine the ability of Parkinson's disease patients to make transitions between movement tasks and force control. In contrast to control subjects, Parkinson's disease patients produced staircase patterns for grip and load forces. Furthermore, a breakdown in the parallel co-ordination between grip and load force was observed for Parkinson's disease patients. These data suggest that Parkinson's disease disrupts the normal feedforward operations responsible for the co-ordination between grip and load forces.
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PMID:The co-ordination and phasing of a bilateral prehension task. The influence of Parkinson's disease. 957 97

The basal ganglia may be involved in bimanual co-ordination. Parkinson's disease (which impairs basal ganglia output) is clinically reported to cause difficulties in the performance of co-ordinated bimanual movements. Nevertheless, any bimanual co-ordination difficulties may be task specific, as experimental observations are equivocal. To infer the role of the basal ganglia in co-ordinating the two arms, this study investigated the bimanual co-ordination of patients with Parkinson's disease. Sixteen Parkinson's disease patients and matched control subjects performed a bimanual cranking task, at different speeds (1 and 2 Hz) and phase relationships. All subjects performed the required bimanual in-phase movement on a pair of cranks, at fast (2 Hz) and slow (1 Hz) speeds. However, the Parkinson's disease patients were unable to perform the asymmetrical anti-phase movement, in which rotation of the cranks differed by 180 degrees, at either speed; but instead reverted to the in-phase symmetrical movement. For Parkinson's disease patients, performance of the in-phase movement was more accurate and stable when an external timing cue was used; however, for anti-phase movement, the external cue accentuated the tendency for patients to revert to more symmetrical, in-phase movements.
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PMID:Bimanual co-ordination in Parkinson's disease. 957 98

Glutamatergic neurotransmission in the subthalamic nucleus (STN) and in the output nuclei of the basal ganglia is critical in the expression of basal ganglia function, and increased glutamate transmission in these nuclei has been implicated in the pathology of Parkinson's disease. In order to determine the precise spatial relationship of subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors to nerve terminals enriched in glutamate or gamma-aminobutyric acid (GABA) in one of the output nuclei, the entopeduncular nucleus (EP), and the STN, postembedding immunolabelling for glutamate receptor subunits and for glutamate and GABA was carried out in the rat. Immunolabelling for the AMPA glutamate receptor subunits 1, 2/3, and 4 (GluR1, GluR2/3, and GluR4) and the NMDA receptor subunit 1 (NR1) was localized predominantly within asymmetrical synapses in both the EP and STN. Quantitative analysis revealed that, on average for the whole population, each of the receptor subunits was evenly distributed along the synaptic specialization. Multiple AMPA receptor subunits and the GluR2/3 and NMDA (NR1) subunits were co-localized within individual synapses. The combination of immunolabelling for glutamate and GABA with the receptor immunolabelling revealed that the majority of axon terminals presynaptic to the receptor-immunoreactive synapses were enriched in glutamate immunoreactivity and were GABA-immunonegative. However, at some NR1- and GluR2/3-positive synapses, the level of glutamate immunoreactivity was low in the presynaptic terminal and, in the STN, some of them were GABA-immunopositive. It is concluded that glutamatergic transmission at individual synapses of different origins in the EP and STN is mediated by a combination ofAMPA and NMDA glutamate receptors.
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PMID:Distribution of glutamate receptor subunits at neurochemically characterized synapses in the entopeduncular nucleus and subthalamic nucleus of the rat. 967 65

To investigate changes in the relation between presynaptic and postsynaptic dopaminergic functions in vivo in both nigrostriatal and mesocortical systems in Parkinson's disease (PD), 10 drug-naive early PD patients were studied twice using positron emission tomography with [11C]CFT (dopamine transporter probe) followed by [11C]SCH 23390 (D1 receptor probe). Regional binding potentials (k3/k4) of [11C]CFT and [11C]SCH 23390 in the striatum (nigrostriatal system) and the orbitofrontal cortex (mesocortical system) were estimated by compartment analyses. Levels of [11C]CFT k3/k4 in the two projection areas were shown to be significantly lower in PD, whereas [11C]SCH 23390 levels remained unchanged. Regression analysis showed that estimates of CFT k3/k4 were positively correlated with those of SCH 23390 k3/k4 in the striatum in normal control, whereas the two binding estimates were less positively correlated in the caudate and inversely correlated in the putamen in PD. No significant correlation was observed in the orbitofrontal cortex in both groups. These results indicated that dopamine transporters and D1 receptors change in parallel in the normal striatal synapses, but the association becomes asymmetrical because of reduction in presynaptic and relative elevation in postsynaptic markers in PD. Alterations in synaptic parallel regulation in the nigrostriatal system might reflect early pathophysiology in the parkinsonian brain.
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PMID:Presynaptic and postsynaptic dopaminergic binding densities in the nigrostriatal and mesocortical systems in early Parkinson's disease: a double-tracer positron emission tomography study. 1055 89

Continuous high frequency stimulation of the ventral intermediate nucleus of the thalamus (Vim), delivered through surgically implanted quadripolar electrodes, alleviates tremor in Parkinson's disease (PD) and essential tremor (ET). The Vim is adjacent to the thalamic reticular nuclei, where sleep spindles originate according to animal models. In order to determine whether Vim stimulation affects sleep spindles, six patients (4 PD, 2 ET), aged 60-69 years, were recorded on a control night and a stimulation night (130 Hz, 2-3 V; right stimulation in five patients and bilateral stimulation in one patient). Stimulation did not modify sleep quality or architecture. Sleep spindles were present and symmetrical in five out of six patients under stimulation. However, in one patient with a sustained 'thalamotomy-like effect' that abolished tremor, spindles were asymmetrical even without stimulation. In each patient, spindle density was similar on both nights (mean+/- SEM: 2.25+/-0. 61 spindles per min of stage 2 sleep vs. 1.84+/-0.31). In an attempt to promote sleep two different patterns of stimulation were applied in the region of ventrooralis posterior and reticularis nuclei in five patients in the awake state. Continuous low frequency stimulation (5 Hz, 0.1 V), and repeated trains of 15 Hz for 1 s every 15 s mimicking the pattern of physiological spindles, each failed to induce sleep or cortical synchronization. We conclude that Vim stimulation, unlike thalamotomy, selectively reduces tremor without altering sleep or sleep spindles. Our results also suggest that low frequency stimulation applied in the region of the reticular nuclei does not induce sleep.
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PMID:Effect of low and high frequency thalamic stimulation on sleep in patients with Parkinson's disease and essential tremor. 1073 90

Regional cerebral blood flow (rCBF) was measured using PET and H2(15)O in Parkinson's disease (PD) patients with predominantly right-sided akinetic-rigid symptoms and in control subjects during the execution of an externally cued motor task either with the left or the right hand. During the execution of the task with the left, non-akinetic, hand, cerebral activation in PD patients appeared similar to that of controls. Activated areas were the primary motor cortex, premotor cortex, parietal cortex and cerebellum. When the task was executed with the right, akinetic, hand cerebral activation in PD patients differed from that of controls subjects. The most important change was a bilateral activation of the primary motor cortex. We conclude that overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients.
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PMID:Overactivation of primary motor cortex is asymmetrical in hemiparkinsonian patients. 1075 20


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