Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide, produced following activation of N-methyl-D-aspartate (NMDA) receptors, may be involved in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity since NMDA receptor antagonists have been shown to prevent MPTP induced nigral cell loss in primates. Common marmosets were treated with either saline or MPTP or L-NGnitro arginine methyl ester (L-NAME) or MPTP and L-NAME. MPTP-treated common marmosets showed motor deficits including bradykinesia, rigidity, and tremor accompanied by a marked loss of tyrosine hydroxylase-immunoreactive neurones in the substantia nigra pars compacta and of [3H]-mazindol binding in the caudate-putamen. MPTP treatment also caused an increase in glial fibrillary acidic protein (GFAP) staining in the substantia nigra compared to controls. However, MPTP treatment did not alter the number of constitutive nitric oxide synthase-immunoreactive neurones in the caudate-putamen. Furthermore, neurones or glial cells immunoreactive for inducible nitric oxide synthase were not observed in the substantia nigra pars compacta following MPTP treatment. L-NAME treatment alone did not produce any behavioural changes in marmosets and did not alter the number of tyrosine hydroxylase-immunoreactive cells in the substantia nigra pars compacta, the number of constitutive nitric oxide synthase-immunoreactive neurones or [3H]-mazindol binding in the caudate-putamen compared to saline-treated control animals. Furthermore, L-NAME did not affect the motor deficits, loss of tyrosine hydroxylase-immunoreactive neurones in the substantia nigra pars compacta, loss of [3H]-mazindol binding in the caudate-putamen, or the increase in GFAP staining in the substantia nigra induced by MPTP treatment of common marmosets. The failure of L-NAME to protect against MPTP-induced toxicity in the marmoset suggests that nitric oxide does not play a major role in such toxicity and casts doubt over the involvement of the NMDA:nitric oxide system in neurodegeneration in MPTP-treated primates.
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PMID:Nitric oxide synthase inhibition and MPTP-induced toxicity in the common marmoset. 918 19

L-DOPA, the precursor of dopamine, remains most effective in the treatment of patients with Parkinson's disease, but prolonged L-DOPA treatment often produces adverse effects, including dyskinesia and psychosis. Dopamine receptors can be divided into two major subtypes, D1 and D2. Might both subtypes of the dopamine receptor be equally relevant to amelioration of parkinsonian symptoms and responsible for the adverse side effects? To address this question, the effects of D1 or D2 receptor agonists alone and in joint administration were examined in MPTP-induced parkinsonian monkeys. The parkinsonian symptoms, such as tremor, bradykinesia and rigidity, and the adverse side effects, such as hyperactivity and aggressiveness, were evaluated independently using different behavioral criteria. The results showed that antiparkinsonian effects can be exerted either by the D1 agonist (SKF 82958) alone or by the D2 agonist (quinpirole) alone, whereas hyperactivity and aggressiveness manifested by dopamine agonists require coactivation of the D1 and D2 receptors. Thus, the antiparkinsonian effect can be dissociated from the adverse effect by therapeutic strategy. It is implied that imbalances in activation of the D1 and D2 receptors may provide a favorable approach for long-term treatment of parkinsonian patients with dopamine drugs.
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PMID:Differential therapeutic effects of dopamine D1 and D2 agonists in MPTP-induced parkinsonian monkeys: clinical implications. 927 96

There is a world-wide renaissance of neurosurgical treatments of Parkinson's disease (PD), based on substantial progress in basic sciences. A model of parallel motor circuitry has identified potential targets for lesioning by clarifying the pathophysiological role of the basal ganglia in PD. The internal globus pallidus (Gpi) is an essential player as it connects to thalamocortical projections and can be disinhibited by overactivity of the nucleus subthalamicus (Nst). Lesioning of these targets has been successful in MPTP damaged primates. There is clinical use of destructive as well as restorative and stimulative technics. Pallidotomy and thalamatomy have evolved by the use of better neuroradiological and electrophysiological targeting. The first technic is used for treatment of rigidity, hypokinesia and dyskinesias, the latter one has proven to be efficient for tremor. Dopaminergic reinnervation and increased dopaminergic output of the striatum has only been seen after transplantation of fetal cells; this method however carries immunological and ethical problems. The continuous high frequency stimulation of basal ganglia is the newest technic; it is highly adaptable to the patient's need and carries a low morbidity profile. Thalamic stimulation is used for the treatment of tremor. The stimulation of Nst and Gpi are proposed for dyskinesias and on/off phenomena. Animal research further focuses on xenotransplantation and implantation of genetically transformed cells or pluripotent precursor cells.--In summary neurosurgical procedures seem to be very promising; however longterm comparison studies are needed to define the best (combination) treatment(s) for the future.
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PMID:[Neurosurgical methods in treatment of Parkinson disease. Current status]. 931 80

The pathophysiology of dystonia is unclear, but several clues implicate striatal dopamine dysfunction. In contrast, the causal relationship between striatal dopamine deficiency and parkinsonism is well defined. We now suggest that parkinsonism or dystonia may occur following striatal dopamine deficiency. Baboons treated with intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) developed transient hemidystonia prior to hemiparkinsonism. The day after MPTP treatment, most animals had spontaneous ipsilateral turning. Within a few days, all developed contralateral hemidystonia, with the arm and leg extended and externally rotated. This transient dystonia preceded hemiparkinsonism with flexed posture, bradykinesia, and postural tremor that persisted for up to 1.5 years. Dystonia corresponded temporally with a decreased striatal dopamine content and a transient decrease in D2-like receptor number. The time course of dystonia and parkinsonism is analogous to lower limb dystonia as the first, frequently transient, symptom of Parkinson's disease in humans. The association of striatal dopamine deficiency with dystonia and parkinsonism implies that other factors influence clinical manifestations.
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PMID:MPTP induces dystonia and parkinsonism. Clues to the pathophysiology of dystonia. 937 34

Five female adult Macaca nemestrina monkeys, given a unilateral intracarotid (ic) infusion of 2.3-3.5 mg of MPTP-HCl, were studied for 6-8 years. Two to 3 days after MPTP, the animals developed hemiparkinsonism characterized by rigidity and flexed posture of the arm contralateral to the side of infusion with episodes of tremor, circling ipsilateral to the lesioned side, a slight balance disturbance, and stooped posture. Rating of parkinsonian features 4 months after ic infusion, and yearly thereafter, did not show any statistically significant changes. The animals maintained their usual appetite and body weight increased normally. Each animal responded to l-DOPA methyl ester with decreased parkinsonian signs and symptoms and increased contralateral turning. In contrast, after control vehicle administration, the animals continued to have the same parkinsonian signs and predominant ipsilateral turns. In three of the five monkeys, contralateral turns after vehicle significantly increased after 6-8 years. Unilateral intracarotid MPTP induced asymmetric motor behavior that remained stable after 6-8 years. Animals that showed an increased frequency of contralateral circling after control vehicle showed a decrease in contralateral turns after l-DOPA methyl ester, suggesting neuroplastic changes over the years.
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PMID:MPTP-Induced hemiparkinsonism in nonhuman primates 6-8 years after a single unilateral intracarotid dose. 971 May 20

Carbon disulfide toxicity is well characterized. The principal target organ is the nervous system, although cardiovascular, reproductive, ophthalmologic, and other effects are also recognized. The neurotoxicity manifests in three ways: encephalopathy, peripheral and cranial nerve dysfunction, and movement abnormalities. This report describes a case of olivopontocerebellar atrophy, a form of multiple system atrophy, developing in an adult after over 30 years of occupational exposure to carbon disulfide. The patient presented with the insidious onset of balance problems, impotence, and irritability, without tremor, cogwheel rigidity, bradykinesia, or changes in facial expression. Over the next few years severe ataxia developed, and the clinical diagnosis was confirmed with computed tomography and magnetic resonance imaging scans. The patient experienced multiple medical complications and died approximately 9 years after diagnosis. This case is consistent with a large body of clinical and experimental literature, much of it 50 years old, showing that carbon disulfide can cause movement disorders. It also serves as a reminder that movement disorders, ranging from parkinsonism to dystonia, are associated with a variety of toxic exposures such as manganese, carbon monoxide, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and medications.
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PMID:Multiple system atrophy following chronic carbon disulfide exposure. 1070 37

Rhesus and vervet monkeys respond differently to treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride neurotoxin (MPTP). Both species develop akinesia, rigidity, and severe postural instability. However, rhesus monkeys only develop infrequent, short episodes of high-frequency tremor, whereas vervet monkeys have many prolonged episodes of low-frequency tremor. After MPTP treatment, the spiking activity of many pallidal neurons became oscillatory and highly correlated. Oscillatory autocorrelation functions were dominated by lower frequencies, cross-correlograms by higher frequencies. The phase shift distribution of the oscillatory cross-correlograms of pallidal cells in MPTP-treated vervet monkey were clustered around 0 phase shift, unlike the oscillatory correlograms in the MPTP-treated rhesus monkey, which were widely distributed between 0 degrees and 180 degrees. Analysis of the instantaneous phase differences between tremors of two limbs in the MPTP monkeys and human parkinsonian patients showed short periods of tremor synchronization. We thus concluded that the rhesus and the vervet models of MPTP-induced parkinsonism may represent the tremulous and nontremulous variants of human parkinsonism. We suggest that the tremor phenomena of Parkinson's disease (PD) are related to the emergence of synchronous neuronal oscillations in the basal ganglia. Finally, the oscillating neuronal assemblies in the pallidum of tremulous parkinsonian primates are more stable (in time and in space) than those of parkinsonian primates without overt tremor.
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PMID:Physiology of MPTP tremor. 982 91

The role of the subthalamic nucleus (STN) in the origin of parkinsonian tremor is discussed. Previous studies in monkeys made parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration suggested a direct participation of the STN in the pathophysiology of tremor. We recorded tremor-related activity in the STN in 12 patients with Parkinson's disease (PD) and found that microstimulation of the sensorimotor region of the nucleus, where these neurons are present, stopped the tremor with a very short latency. Long-term treatment by means of bilateral deep-brain stimulation (DBS) in the same 12 patients led to a significant reduction of tremor as well as other cardinal features of PD. This effect was blindly assessed at 3 months after implantation. In another group of seven patients, a unilateral lesion of the STN was performed. Both postural and resting tremor were significantly improved on the limbs contralateral to the lesion side. In three patients, tremor disappeared completely after 12 months of follow up. The electrophysiologic data and therapeutic effect of inactivating the STN strongly indicated that this structure is directly involved in the origin of parkinsonian tremor, as suggested by the MPTP model.
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PMID:The subthalamic nucleus and tremor in Parkinson's disease. 982 6

The recent resurgent interest in functional surgery for the treatment of Parkinson's disease (PD) has focused on the effects on akinesia and levodopa-induced dyskinesia. Stimulation of the subthalamic nucleus (STN) improves akinesia and rigidity but its effects on tremor have not been studied. The objective of this study was to assess the efficacy of STN stimulation on tremor in patients with the complete parkinsonian triad with motor fluctuations. Of 27 consecutive patients with STN stimulation (26 bilateral), 15 exhibited tremor rated at least 2/4 according to item 20 (rest tremor) of the Unified Parkinson's Disease Rating Scale (UPDRS) in at least one limb. The mean preoperative tremor score was 11.3+/-5.6 in off-drug and 1.2+/-2.4 in on-drug conditions. The postoperative tremor scores at the last follow up (from 1-12 months) were 2.2+/-2.2 off-drug/on-stimulation and 0.2+/-0.4 on-drug/on-stimulation. Both rest and action tremors were improved in all patients. The UPDRS tremor score was reduced by 80%, rigidity score by 65%, and akinesia score by 51% on average. For the three symptoms, the stimulation effect was close to that induced before surgery by a suprathreshold dose of levodopa given in the morning. STN stimulation can be considered an interesting alternative to thalamic or internal pallidal surgery even in PD patients with severe high-amplitude tremor. In keeping with electrophysiological data in monkeys rendered parkinsonian by MPTP injections, our results emphasize the importance of the oscillation of a neuronal loop involving the STN in the pathophysiology of parkinsonian tremor.
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PMID:Treatment of tremor in Parkinson's disease by subthalamic nucleus stimulation. 982 14

We have studied the effect of unilateral autografts of carotid body cell aggregates into the putamen of MPTP-treated monkeys with chronic parkinsonism. Two to four weeks after transplantation, the monkeys initiated a progressive recovery of mobility with reduction of tremor and bradykinesia and restoration of fine motor abilities on the contralateral side. Apomorphine injections induced rotations toward the side of the transplant. Functional recovery was accompanied by the survival of tyrosine hydroxylase-positive (TH-positive) grafted glomus cells. A high density of TH-immunoreactive fibers was seen reinnervating broad regions of the ipsilateral putamen and caudate nucleus. The nongrafted, contralateral striatum remained deafferented. Intrastriatal autografting of carotid body tissue is a feasible technique with beneficial effects on parkinsonian monkeys; thus, this therapeutic approach could also be applied to treat patients with Parkinson's disease.
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PMID:Recovery of chronic parkinsonian monkeys by autotransplants of carotid body cell aggregates into putamen. 1023 Jul 94


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