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)

The 2-deoxyglucose metabolic mapping technique has been used to investigate the neural mechanisms which underlie the symptoms of Parkinsonism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. In six cynomolgus monkeys, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was either (a) administered intravenously to induce generalized Parkinsonism, or (b) infused into one carotid artery to induce unilateral Parkinsonism. Post-mortem examination revealed profound cell loss from the substantia nigra, pars compacta either bilaterally or unilaterally in the two groups, respectively. In addition, there was pathological involvement of the ventral tegmental area and locus coeruleus in animals receiving intravenous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 2-Deoxyglucose autoradiography revealed widespread changes in 2-deoxyglucose uptake in the brains of parkinsonian animals when compared to controls. Most of these changes were in basal ganglia and related structures and were qualitatively similar in the two groups of experimental animals. Prominent increases in 2-deoxyglucose uptake were observed in the lateral segment of the globus pallidus (24-27%), the ventral anterior and ventral lateral nuclei of the thalamus (14-22%) and the nucleus tegmenti pedunculopontinus of the caudal midbrain (17-69%). A profound decrease (17-26%) in 2-deoxyglucose uptake was observed in the subthalamic nucleus. We propose these data to indicate that in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism there is the following pattern of abnormal neuronal activity in basal ganglia circuitry: (i) increased activity in the projection from the putamen to the lateral segment of the globus pallidus; (ii) decreased activity in the projection from the putamen to the medial segment of the globus pallidus; (iii) decreased activity in the projection from the lateral segment of the globus pallidus to the subthalamic nucleus; (iv) increased activity in the projection from the subthalamic nucleus to the globus pallidus; and (v) increased activity in neurons of the medial segment of the globus pallidus projecting to the ventral anterior/ventral lateral thalamus and the pedunculopontine nucleus. These results are compared to the 2-deoxyglucose uptake findings in previous studies from this laboratory in hemiballism and hemichorea in the monkey. The central importance of the subthalamic nucleus in all three conditions is proposed, and supportive evidence for the excitatory nature of subthalamic efferent fibres is adduced.
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PMID:Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 258 50

Hyperactivity of the subthalamic nucleus (STN) is major characteristic of parkinsonism secondary to substantia nigra lesions. Interruption of the STN-internal pallidum (GPi) pathway is a new stereotactic target for Parkinson's disease. We have studied the antiparkinsonian efficacy of STN lesions in MPTP-treated monkeys. Four rhesus monkeys were made parkinsonian by MPTP (i.v. 0.15 +/- 1 mg/kg) administration over 3 months. Unilateral subthalamotomy (kainic acid) was performed by a standard stereotactic method. Severity was rated from 0 (normal) to V by fine manual motor tests. Three monkeys (severity state III/IV) showed marked improvement in spontaneous activity, facial expression and manual dexterity bilaterally but significantly greater in the limb contralateral to the lesion. Mild hemichorea was present in 2 and hemiballism in one. L-Dopa treatment (50 mg b.i.d.) enhanced the hemidyskinesias moderately. The therapeutic effect has persisted for over 8 months postsurgery. Monkey No.4 (severity stage V) showed chorea in the lower limb contralateral to the lesion but no improvement and died a few days later. Subthalamotomy improves parkinsonism in moderately severe parkinsonian monkeys. Dyskinesia might be a persistent complication.
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PMID:Subthalamotomy improves MPTP-induced parkinsonism in monkeys. 763 Oct 95

Nineteen Macaca fascicularis monkeys were divided into four different groups: Group A (n = 3), control; Group B (n = 3), monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Group C (n = 8), animals treated with MPTP in which the subthalamic nucleus (STN) was unilaterally lesioned by kainic acid injection; in Group D (n = 5), the STN was lesioned prior to MPTP administration. Subthalamotomy resulted in a bilateral improvement of tremor, spontaneous activity, bradykinesia (evaluated by a manual motor test) and freezing in Group C. All these monkeys developed hemichorea contralateral to the lesion. The improvement was maintained and the hemichorea continued until death. The monkeys in group D showed severe hemiballism which persisted throughout MPTP administration and developed parkinsonian signs mainly on the side ipsilateral to the lesion. Analysis of the in situ hybridization of the mRNA coding for glutamic acid decarboxylase (GAD) of MPTP monkeys showed a significant increase in the mean density of silver grains over every labelled neuron in the globus pallidum lateralis (56.8% over control) as well as the globus pallidus medialis (GPM) (45.7% over control) and the substantia nigra reticulata (SNR) (35.8% over control). No significant change was observed in the thalamic nucleus reticularis. Subthalamotomy (Groups C and D) produced a significant reduction in mRNA GAD expression on the side of the lesion in the GPM and the SNR (34% and 42.3%, respectively) with respect to the ipsilateral (non-lesioned) side and also when compared with parkinsonian monkeys. These results confirm and expand, at the cellular level, the paramount role of STN hyperactivity in the pathophysiology of parkinsonism. The therapeutic consequences of these findings for surgical treatment of Parkinson's disease are discussed.
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PMID:Subthalamotomy in parkinsonian monkeys. Behavioural and biochemical analysis. 893 92

The subthalamic nucleus (STN) currently is considered to play a key role in the pathophysiological origin of the parkinsonian state and is therefore the main target for surgical treatment of Parkinson's disease. The authors review the incidence of hemichorea/ballism (HCB) as a complication of thalamotomy, pallidotomy or campotomy procedures before the introduction of levodopa therapy, including the few reported cases accompanied by a neuropathological study. The literature shows that only a small number of parkinsonian patients with HCB had a lesion of the STN. Preliminary data in Parkinson's disease patients submitted to a subthalamotomy with current functional stereotaxy also indicate that HCB is a very rare complication. To explain this observation, we suggest that the parkinsonian state is characterized by an increased threshold for the induction of dyskinesia following STN lesioning. This arises as a consequence of reduced activity in the 'direct' GABA projection to the globus pallidus medialis (GPm) which accompanies dopamine depletion. Lesioning of the STN reduces excitation of the GPm, and theoretically this should induce dyskinesias. However, an STN lesion also, simultaneously, further reduces the hypoactivity in the globus pallidus lateralis (GPl) that is a feature of Parkinson's disease, and hence may compensate for GPm hypoactivity, thus self-stabilizing basal ganglia output activity and reducing the risk of HCB. We conclude that lesioning of the STN in Parkinson's disease is a feasible approach in some circumstances.
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PMID:The subthalamic nucleus, hemiballismus and Parkinson's disease: reappraisal of a neurosurgical dogma. 1113 83

Alterations in the basal ganglia-thalamocortical "motor" circuit activity, have been proposed to explain many features associated with hypokinetic and hyperkinetic movement disorders. We describe the firing pattern of the globus pallidus pars interna in a Parkinson disease's patient who developed Hemichorea-Ballismus subsequent to ipsilateral subthalamotomy, and compare findings to those from PD patients submitted to pallidotomy while in the OFF-medication state. Single units obtained from extracellular recordings were extracted and mean discharge frequency, interspike interval and coefficient of variation (defined as Tonicity Score) were computed. Discharge density histograms, analysis of distribution and spectral analysis were also performed. Mean firing frequency showed no significant difference between PD patients in the OFF state and the patient we report. However, a significant difference in tonicity was found for this patient characterized by a regular, non-bursting firing pattern. The findings indicate that in HB caused by lesions to STN in the parkinsonian state, GPi firing rates can be similar to and firing pattern more regular than those observed in GPi of PD patients OFF-medication with intact STN.
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PMID:Neuronal discharge patterns in the globus pallidus pars interna in a patient with Parkinson's disease and hemiballismus secondary to subthalamotomy. 2178 35