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)

Fetal substantia nigra (SN) cells were transplanted into the caudate nucleus (CN) of four vervet monkeys (Cercopithecus aethiops sabaeus) that had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP treatment appears to produce a syndrome similar to that observed in patients with idiopathic Parkinson's disease. Normal and parkinsonian behaviors were quantitated by trained observers 5 days/week. Twenty-eight behaviors based on previous factor analyses were individually scored and rated. Parkinsonian signs included freezing, head and limb tremor, difficulty in eating, delayed initiation of movement, poverty of movement, tremor that stopped with intention, decreased response to threats, and lying immobile in the cage. These signs were combined to give an overall rating of parkinsonism. A summary measure of 'normal' healthy behavior was also examined, including such behaviors as yawning, scratching, self-grooming, shifting, and eating. Overall ratings of parkinsonism increased and those of healthy behavior decreased after MPTP. In the 4 monkeys grafted with fetal SN cells into the CN, behavior returned to pre-treatment levels by the time of sacrifice (2, 5, or 7.5 months after grafting). Three control subjects were transplanted with either SN cells into an inappropriate brain site (cortex) or inappropriate, non-dopaminergic, cells (cerebellar) into the CN. Subjects were also compared with three control animals that did not receive MPTP but received cryopreserved or fresh SN and other cells into the CN. Only MPTP-treated subjects that received SN cells into the CN showed evidence of a reversal of the MPTP syndrome after transplantation. In addition, grafting in animals that were not MPTP-treated did not appear to affect behavior. This paper reports the specific behavioral effects of severe MPTP toxicity that were or were not reversed after transplantation and suggests that only fetal SN cells grafted into the CN may be able to reverse behavioral deficits in MPTP-treated monkeys.
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PMID:Grafting of fetal substantia nigra to striatum reverses behavioral deficits induced by MPTP in primates: a comparison with other types of grafts as controls. 189 83

To assess the stability of neural deficits produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the performance of monkeys on an object retrieval (detour) task was studied. The task required retrieval of a banana slice from a transparent box open on one side and fastened to a tray in front of the cage. The orientation of the open side, position on the tray, and position of the banana in the box were manipulated to vary the difficulty of the trials. Six African green monkeys (Cercopithecus aethiops sabaeus) were treated with MPTP (1.5-1.6 mg/kg cumulative doses over 4-5 days) and compared with 5 saline-treated control monkeys. The MPTP-treated monkeys had no gross neurological deficits but did have motor and cognitive deficits during acquisition of the object retrieval task 8-12 months after treatment (J. R. Taylor, Elsworth, Roth, Sladek, & Redmond, in press). Performance on the task was examined for 3 months after it had been learned. The MPTP-treated subjects reached at the barrier (transparent side) significantly more than controls and were less successful at retrieving the reward on the 1st reach than controls. Although they took longer to initiate the reach and had more motor problems than controls, they were as likely as controls to retrieve the reward in the end. These deficits remained stable throughout testing. An opaque but otherwise identical box was used randomly on some trials. MPTP-treated subjects decreased barrier reaches to control levels on trials in which the opaque box was used, whereas motor problems increased compared with trials in which the transparent box was used. The task can detect subtle performance deficits similar to those found in Parkinson's disease.
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PMID:Cognitive and motor deficits in the performance of an object retrieval task with a barrier-detour in monkeys (Cercopithecus aethiops sabaeus) treated with MPTP: long-term performance and effect of transparency of the barrier. 220 26

Rats were trained on place or cue spatial navigation tasks in a swimming pool and then given the neuroleptic, alpha-flupentixol. Initial experiments showed that regardless of testing schedule, including blocks of trials given concurrently or separated by 7 or 30 days, drugged rats showed a trial-by-trial decay in latency and accuracy of responding although they continued to swim. The rate of decay increased with increases in drug dosage. Further experiments showed that: 1) Performance decay was specifically related to conditioned components of the test environment. Animals required to swim in a different test, or to struggle, showed less decay than rats exposed to the test platform only or required to perform all aspects of the task. 2) Decay was not due to nonspecific effects of neuroleptic treatment because rats injected and replaced in their home cage, and then subsequently reinjected and tested performed like rats treated and tested for the first time. 3) A trial-dependent decay of performance was also obtained in hippocampectomized and decorticate rats, suggesting that at least part of the major action of the drug is on subcortical systems. The results are discussed with respect to hypotheses of neuroleptic action and with respect to their possible relevance to experience-dependent changes in animal analogues of Parkinson's disease. Finally, it is suggested that behavior may be organized in subsystems, which when active, become selectively sensitive to neuroleptics.
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PMID:Training-dependent decay in performance produced by the neuroleptic cis(Z)-flupentixol on spatial navigation by rats in a swimming pool. 273 32

The non-human primate models of Parkinson's disease which have been developed using the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine) have proven to be either unstable or variable, or to display only a limited subset of parkinsonian features. The present study examined a new two-stage lesion approach in which MPTP was administered via the carotid arteries. The first infusion through one artery produced a hemiparkinsonian state and was followed several months later by a second MPTP infusion into the contralateral carotid artery to induce bilateral parkinsonism. Animals receiving lesions were evaluated using a battery of tests which included a monkey parkinsonism rating scale, a movement time-task and continuous monitoring of home cage activity. All animals monitored showed significant decreases in activity levels of up to 95% following the second lesion. These decreased activity levels remained stable throughout the observation period of up to 12 months postlesion. In addition to the decreased home cage activity, bilaterally lesioned animals displayed bilateral parkinsonian features including akinesia, bradykinesia, rigidity, tremor and balance and gait disturbances which were stable, following an acute period of up to 45 days, for the remainder of the study. Administration of levodopa increased activity levels and reduced motor dysfunctions. Thus, a two-stage bilateral lesion approach, utilizing the neurotoxin MPTP, appears to provide a less variable and relatively stable model of bilateral Parkinson's disease in nonhuman primates. Treated animals display the cardinal features of parkinsonism and respond appropriately to the standard antiparkinsonian drug, levodopa.
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PMID:Developing a stable bilateral model of parkinsonism in rhesus monkeys. 843 10

Breathing was investigated in 14 male subjects with Parkinson's disease and 14 healthy male control subjects. Kinematic, spirometric, acoustic, and pressure data were used to assess function during resting tidal breathing, reading aloud, and monologue production. Data were collected at two times during the drug cycle for subjects with Parkinson's disease. During resting tidal breathing, subjects with Parkinson's disease, on average, had a faster breathing rate, greater minute ventilation, and smaller relative contribution of the rib cage to lung volume change than did healthy control subjects. During speech breathing, rib cage volume was smaller and abdominal volume was larger at initiation of the breath groups for subjects with Parkinson's disease than for healthy control subjects. Subjects with Parkinson's disease produced fewer words and spent less time producing speech per breath group and tended to have a faster interpause speech rate than did healthy control subjects. There was no difference between groups for duration of inspirations between speech breath groups. Oral pressure was lower for subjects with Parkinson's disease but estimated tracheal pressure did not differ between the two subject groups. Few differences were found between the two times in the drug cycle for resting and speech breathing. Results provide indirect evidence for reduced relative compliance of the rib cage to the abdomen for subjects with Parkinson's disease as compared to healthy control subjects. In addition, the results support the possibility of inadequate valving of the air stream for subjects with Parkinson's disease.
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PMID:Speech breathing in Parkinson's disease. 848 22

Although the role of dopamine dysfunction is well established in Parkinson's disease, the effect of nigrostriatal degeneration on motor performance during normal aging is less well understood. In this study, aged rhesus monkeys (25-27 years old) displayed significant impairments relative to young (3-5 years old) cohorts in motor function as assessed on a fine motor task and home cage activity. Additionally, the clinical motor function of aged monkeys was impaired relative to young monkeys as assessed on a clinical rating scale. Unbiased stereologic measurements of the substantia nigra revealed a significant age-related loss of tyrosine hydroxylase-immunoreactive (TH-ir; 50.3%) and dopamine transporter-immunoreactive (DAT-ir; 33.2%) nigral neurons. The monkeys performance on the fine motor task and on the clinical rating scale was correlated with TH-ir neuronal counts. The number of DAT-ir nigral neurons was correlated with activity and clinical rating scale scores. Our results suggest that age-related motor impairments in nonhuman primates are associated with spontaneous decreases in TH-ir and DAT-ir nigral cells. The correlation of motor deficits with the loss of TH-ir and DAT-ir nigral neurons suggests that aged nonhuman primates may provide a useful model for mimicking changes seen in human aging and early Parkinson's disease.
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PMID:Age-related declines in nigral neuronal function correlate with motor impairments in rhesus monkeys. 982 52

The improvement in motor performance resulting from levodopa administration in patients with Parkinson's disease (PD) provides the opportunity to investigate ventilatory changes brought about by the disease. The aim of this study has been to investigate these changes in order to specify the mechanisms of the impairment in breathing in PD. Breathing patterns at rest were investigated in 11 patients with idiopathic PD both before (OFF) and after (ON) administration of levodopa at a dose improving their motor performance by at least 30%. Airflow (Fleisch head mounted on a mask), rib cage and abdomen movements (inductance plethysmography) were recorded in the OFF condition 1 h after subjects woke up. Subjects then received levodopa and a new set of recordings was obtained 1 h later, in the ON condition. Breath-by-breath processing of recordings was carried out, and tidal volume (VT), inspiratory (TI) and expiratory (TE) durations were measured. The main finding was a lengthening of TI resulting in a decrease in ventilation and in VT/TI, and an increase in TI/TTOT in the ON compared to the OFF condition. In the ON condition abnormal rib cage-abdomen plots patterns were found in four out of six subjects. A hypothesis on the effect of PD on breathing is proposed on grounds of normal diaphragmatic activity but impaired activity of the other respiratory muscles and more specifically the intercostal muscles.
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PMID:Breathing pattern in patients with Parkinson's disease. 1064 60

Bradykinesia and rigidity are the symptoms that most directly correlate with loss of striatal dopamine in Parkinson's disease. In the hemiparkinsonian (HP) monkey, this is represented by paucity of movement as measured by coli puterized movement analysis, diminished manual dexterity on clinical examination, and diminished performance on operant behavioral tasks. The present study used an MPTP-induced HP model in rhesus monkeys to evaluate the effectiveness of adrenal medullary and peripheral nerve co-grafts in diminishing parkinsonian symptoms. Unoperated controls (N = 4), surgical controls with caudate lesioning (N = 4), and caudate co-grafted (N = 4) HP monkeys demonstrated diminished movement in the home cage following MPTP. This behavior persisted in unoperated controls, but improved in both surgical control and co-grafted monkeys. Functional hand dexterity evaluations demonstrated similar impairment in all three groups but only surgical controls and co-grafted monkeys demonstrated improvement. In general, rotational behavior in response to apomorphine was consistent with recovery of function in surgical controls and co grafted monkeys, but marked between-subject variability precluded group statistical analyses. None of the monkeys could perform the operant task using the affected limb following MPTP. However, the performance of two co-grafted animals demonstrated partial recovery. L-dopa improved operant performance, demonstrating a dopaminergic component to the task. The results demonstrate recovery of behavioral function after surgical treatment, with adrenal co-grafted monkeys showing the greatest degree of improvement.
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PMID:Behavioral evaluation of hemiparkinsonian MPTP monkeys following dopamine pharmacological manipulation and adrenal co-graft transplantation. 1114 58

Patients with Parkinson's disease (PD) may develop pulmonary dysfunction, but the pathogenesis remains unclear. We investigated a correlation between thoracoabdominal movements and pulmonary function in seven patients with PD and 14 healthy controls. We measured vital capacity (VC) and forced vital capacity (FVC) using an autospirometer, and measured chest and abdominal movements using a respiratory inductance plethysmography by fixing transducers on the rib cage and umbilicus. Patients with PD had significantly decreased % VC (90.3 +/- 17.1 vs 105.8 +/- 13.9%), chest movement (271.3 +/- 79.6 vs. 375.2 +/- 126.7% VT) and abdominal movement (217.6 +/- 93.5 vs. 247.4 +/- 100.2% VT) with 100% VT being an average volume of chest and abdomen at rest during measurement of VC. Patients with PD also had significantly decreased % FVC (74.4 +/- 20.6 vs. 97.6 +/- 14.1%), chest movement (246.2 +/- 115.2 vs. 344.5 +/- 126.4% VT) and abdominal movement (160.3 +/- 105.6 vs 207.6 +/- 104.7% VT) with 100% VT being an average volume of chest and abdomen at rest during forced maximal inspiration. Based on the results, we conclude that a reduction of % VC in patients with PD correlated with chest movements, while a reduction of % FVC correlated with abdominal movement in patients with PD.
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PMID:Influence of thoracoabdominal movement on pulmonary function in patients with Parkinson's disease: comparison with healthy subjects. 1122 48

1. This study was undertaken to elucidate dopaminergic mechanisms underlying bladder hyperactivity in a rat model of Parkinson's disease (PD) induced by a unilateral 6-OHDA injection into the substantia nigra pars compacta. 2. In 6-OHDA-lesioned rats, voided volume per micturition (0.41+/-0.04 ml, mean+/-s.e.m.) measured during 24 h in a metabolic cage was significantly smaller than in sham-operated rats (0.67+/-0.07 ml). 3. Cystrometrograms (CMG) in conscious animals revealed significantly smaller bladder capacity (BC) (0.46+/-0.03 ml) in 6-OHDA-lesioned rats than in sham rats (0.72+/-0.06 ml). 4. SKF38393 (D1/D5 receptor agonist, i.v.) significantly increased BC in 6-OHDA rats without apparent effects in sham rats. SKF38393 applied intracerebroventricularly (i.c.v.) under urethane anesthesia also increased BC in 6-OHDA-lesioned rats and by a smaller increment in sham rats. 5. In contrast, quinpirole (D2/D3/D4 receptor agonist, i.v.) significantly reduced BC in sham and 6-OHDA-lesioned rats. Intrathecal injection of quinpirole similarly reduced BC in sham and 6-OHDA-lesioned rats. 6. PD128907 (D(3)-receptor agonist) did not have significant effects on BC in 6-OHDA-lesioned rats. 7. These results indicate that a rat model of PD exhibited bladder hyperactivity as observed in patients with PD, and that stimulation of D1/D5 dopamine receptors at a supraspinal site can suppress bladder hyperactivity in PD, whereas stimulation of D2/D4, but not D3, dopamine receptors had the opposite effect to reduce bladder capacity. Thus, D1/D5 dopamine receptor agonists might be effective in treating neurogenic bladder hyperactivity in PD.
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PMID:Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway. 1292 29


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