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 discovery of rapid eye movement (REM) sleep by Aserinsky and Kleitman in 1953 initiated the impetus for sleep research and specifically the investigations of the effects of REM sleep deprivation (RSD) on animal and human behavior. The behavioral effects of RSD include the enhancement of motivational and "drive"-related behaviors. In laboratory animals, RSD has been reported to increase appetite, sexual behavior, aggressiveness, and locomotor activity. Moreover, RSD reportedly improves mood in patients with endogenous depression and heightens appetite and sexual interest in normal subjects. Since "drive"-related behaviors are thought to involve activation of limbic dopaminergic reward sites, RSD may enhance motivational behaviors through an action on limbic dopaminergic functions. In the present communication, we present two patients (one with multiple sclerosis and the other with Parkinson's disease) in whom treatment with magnetic fields produced behavioral effects which paralleled those observed in REM-sleep-deprived animals and humans. We propose, therefore, that the behavioral and mental effects of treatment with magnetic fields may be mediated via RSD and, by inference, involve activation of limbic dopaminergic reward sites.
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PMID:Magnetic fields mimic the behavioral effects of REM sleep deprivation in humans. 134 92

To clarify the roles of dopamine D1 and D2 receptors in behavioral symptoms of Parkinson's disease, antiparkinsonian effects of various dopamine agonists in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian monkeys were investigated with regard to induction of hyperactivity such as excitability, irritability and aggressiveness. The non-selective dopamine agonist apomorphine ameliorated the parkinsonism, but induced marked hyperactivity dose-dependently. Pretreatment with either the dopamine D1 antagonist SCH 23390 or the dopamine D2 antagonist sulpiride markedly suppressed the apomorphine-induced hyperactivity with slight attenuation of the antiparkinsonian effects. Both the dopamine D2-receptor agonist quinpirole and the dopamine D1-receptor agonist SKF 82958 ameliorated the parkinsonism in a dose-dependent manner with a slight induction of hyperactivity. Combination treatment of a threshold dose of quinpirole with that of SKF 82958 augmented the antiparkinsonian effects without a marked induction of hyperactivity. However, the combination treatment at higher doses induced marked hyperactivity accompanied by augmented antiparkinsonian effects. These results suggest that stimulation of either central dopamine D1 or D2 receptors is requisite for the antiparkinsonian effects and concurrent strong stimulation of both central dopamine D1 and D2 receptors causes marked hyperactivity which may be predictive of dopaminergic psychiatric side effects.
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PMID:Behavioral involvement of central dopamine D1 and D2 receptors in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys. 761 86

The optimal combination of a dopamine D2 agonist and a D1 agonist was evaluated for symptomatic treatment of Parkinson's disease. Behavioral effects of combination treatment of the full D2 agonist quinpirole or the partial D2 agonist terguride with the full D1 agonist SKF 82958 [(I) 6-Chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetra-hydro-1H-3-benzazepine] were investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys with attention to the induction of hyperactivity such as irritability, excitability and aggressiveness and of dyskinesias such as licking of paws, chewing and biting. Both quinpirole and SKF 82958 alone improved the parkinsonism with a slight induction of the hyperactivity and dyskinesias. Terguride also improved the parkinsonism but did not induce the hyperactivity and dyskinesias. Combination treatment of quinpirole with SKF 82958 not only showed a tendency to augment the antiparkinsonian effects but also induced the marked hyperactivity and dyskinesias. On the other hand, combination treatment of terguride with SKF 82958 also augmented the antiparkinsonian effects but did not induce any hyperactivity and dyskinesias. These findings suggest that combination therapy with a partial D2 agonist and a full D1 agonist or monotherapy with a dopamine agonist that has both partial D2 and full D1 agonist properties might be beneficial for treating motor dysfunction in Parkinson's disease without inducing dopaminergic side effects.
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PMID:Combination treatment of the partial D2 agonist terguride with the D1 agonist SKF 82958 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian cynomolgus monkeys. 771 82

Behavioral effects of terguride, a partial dopamine D2 agonist, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys were compared with those of the dopamine agonist apomorphine and the dopamine antagonist haloperidol. Terguride alone ameliorated the parkinsonism without inducing any sign of excitability, irritability, or aggressiveness (hyperactivity). Apomorphine alone also ameliorated the parkinsonism but induced marked hyperactivity. Haloperidol alone caused worsening of the parkinsonism, inducing transient eyelid closure. In combination with apomorphine, terguride suppressed the hyperactivity induced by apomorphine without reducing its antiparkinsonian effects. Pretreatment with haloperidol suppressed both the antiparkinsonian effects and the hyperactivity induced by apomorphine. Terguride thus exhibits both antiparkinsonian and antihyperactivity effects in a monkey model of Parkinson's disease, suggesting that terguride might be beneficial for treating motor dysfunction and dopaminergic psychosis in advanced Parkinson's disease.
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PMID:Effects of terguride, a partial D2 agonist, on MPTP-lesioned parkinsonian cynomolgus monkeys. 809 31

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

The authors report the underestimated cognitive, mood, and behavioral complications in patients who have undergone bilateral contemporaneous pallidotomy, as seen in their early experience with functional neurosurgery for Parkinson's disease (PD) that is accompanied by severe motor fluctuations before pallidal stimulation. Four patients, not suffering from dementia, with advanced (Hoehn and Yahr Stages III-IV), medically untreatable PD featuring severe "on-off" fluctuations underwent bilateral contemporaneous posteroventral pallidotomy (PVP). All patients were evaluated according to the Core Assessment Program for Intracerebral Transplantations (CAPIT) protocol without positron emission tomography scans but with additional neuropsychological cognitive, mood, and behavior testing. For the first 3 to 6 months postoperatively, all patients showed a mean improvement of motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS), in the best "on" (21%) and worst "off" (40%) UPDRS III motor subscale, a mean 30% improvement in the UPDRS II activities of daily living (ADL) subscore, and 60% on the UPDRS IV complications of treatment subscale. Dyskinesia disappeared almost completely, and the mean daily duration of the off time was reduced by an average of 60%. Despite these good results in the CAPIT scores, one patient experienced a partially regressive corticobulbar syndrome with dysphagia, dysarthria, and increased drooling. No emotional lability was found in this patient, but he did demonstrate severe bilateral postoperative pretarsal blepharospasm (apraxia of eyelid opening), which interfered with walking and which required treatment with high-dose subcutaneous injections of botulinum toxin. No patient showed visual field defects or hemiparesis, but postoperative depression, changes in personality, behavior, and executive functions were seen in two individuals. Postoperative abulia was reported by the family of one patient, who lost his preoperative aggressiveness and drive in terms of ADL, speech, business, family life, and hobbies, and became more sleepy and fatigued. One patient reported postoperative mental automatisms, such as compulsive mental counting, and circular thoughts and reasoning during off phases; postoperative depression was found in two patients. However, none of the patients demonstrated these symptoms during intraoperative microelectrode stimulation. These findings are compatible with previous reports on bilateral pallidal lesions. A progressive lowering of UPDRS subscores was seen after 12 months, consistent with the progression of the disease. Bilateral simultaneous pallidotomy may be followed by emotional, behavioral, and cognitive deficits such as depression, obsessive-compulsive disorders, and loss of psychic autoactivation-abulia, as well as disabling corticobulbar dysfunction and apraxia of eyelid opening, in addition to previously described motor and visual field deficits, which make this surgery undesirable even though significant improvement in motor deficits can be achieved.
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PMID:Bilateral contemporaneous posteroventral pallidotomy for the treatment of Parkinson's disease: neuropsychological and neurological side effects. Report of four cases and review of the literature. 1070 52

Historically, in vivo imaging methods have largely relied on imaging gross anatomy. More recently it has become possible to depict biological processes at the cellular and molecular level. These new research methods use magnetic resonance imaging (MRI), positron emission tomography (PET), near-infrared optical imaging, scintigraphy, and autoradiography in vivo and in vitro. Of primary interest is the development of methods using MRI and PET with which the progress of gene therapy in glioblastoma (herpes simplex virus-thymidine kinase) and Parkinson's disease can be monitored and graphically displayed. The distribution of serotonin receptors in the human brain and the duration of serotonin-receptor antagonist binding can be assessed by PET. With PET, it is possible to localize neurofibrillary tangles (NFTs) and beta-amyloid senile plaques (APs) in the brains of living Alzheimer disease (AD) patients. MR tracking of transplanted oligodendrocyte progenitors is feasible for determining the extent of remyelinization in myelin-deficient rats. Stroke therapy in adult rats with subventricular zone cells can be monitored by MRI. Transgene expression (beta-galactosidase, tyrosinase, engineered transferrin receptor) can also be visualized using MRI. Macrophages can be marked with certain iron-containing contrast agents which, through accumulation at the margins of glioblastomas, ameliorate the visual demarcation in MRI. The use of near-infrared optical imaging techniques to visualize matrix-metalloproteinases and cathepsin B can improve the assessment of tumor aggressiveness and angiogenesis-inhibitory therapy. Apoptosis could be detected using near-infrared optical imaging representation of caspase 3 activity and annexin B. This review demonstrates the need for neurohistological research if further progress is to be made in the emerging but burgeoning field of molecular imaging.
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PMID:Molecular imaging: Bridging the gap between neuroradiology and neurohistology. 1502 22

To determine whether apolipoprotein alleles (APOE) influence behavioral and psychological signs and symptoms of dementia (BPSD), we initiated a prospective, longitudinal study. Patients with Alzheimer's disease (AD) (N=186), frontotemporal dementia (FTD) (N=29), mixed dementia (MXD) (N=28), dementia with Lewy bodies (DLB) (N=11) and Parkinson's disease dementia (PDD) (N=7) were included. Blood was collected for DNA extraction and APOE genotyping. Behavioral assessments were performed at baseline and semi-annually thereafter, using behavioral assessment scales (Middelheim frontality score, behavioral pathology in Alzheimer's disease rating scale (Behave-AD)). In FTD patients, we identified dose dependent effects of APOE epsilon4 on the Behave-AD total and cluster aggressiveness scores. APOE epsilon2 was associated with a higher score on the Behave-AD cluster delusions in PDD/DLB patients. No APOE effects on frequency or severity of BPSD in AD and MXD patients were found. In conclusion, APOE has disease-specific effects on BPSD in FTD and PDD/DLB patients, given the reported associations of APOE epsilon4 with aggression (FTD) and of APOE epsilon2 with delusions (PDD/DLB).
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PMID:Dose dependent effect of APOE epsilon4 on behavioral symptoms in frontal lobe dementia. 1639 13

The cognitive status of patients with Parkinson's disease (PD) who developed pathological gambling (PG) during dopamine replacement therapy has been poorly explored. We compared clinical and cognitive features of 21 consecutive PD patients with active PG (PD-PG) versus 42 PD controls of similar disease duration without any impulse control disorder. All patients underwent full neuropsychological testing to evaluate executive and other frontal lobe-related functions, attention, learning and memory, language, visuospatial abilities and neuropsychiatric status [using Geriatric Depression Scale (GDS) and Neuropsychiatric Inventory (NPI)] as well as the South Oaks Gambling Screen Scale (SOGS). PD-PG were younger (60.4 vs. 64.9, p = 0.01) and more frequently of male gender (85 vs. 57%, p = 0.02). The two groups did not differ in medication dosages and kind of dopamine agonist. PD-PG had higher MMSE (29.1 vs. 27.4, p = 0.02) and performed better at Rey Auditory Verbal learning Test (45.9 vs. 40.4, p = 0.04), verbal phonemic fluencies (38.7 vs. 31.8, p = 0.02), verbal semantic fluencies (44.9 vs. 37.4, p = 0.01) and attentive matrices (47.6 vs. 43.5, p = 0.05) while the remaining cognitive performances were comparable to controls. Moreover, based on the NPI, PD-PG had higher aggressiveness, irritability, disinhibition and eating disorders than controls. In conclusion the occurrence of PG in our cohort of patients with PD was associated with preserved executive functions.
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PMID:Cognitive status of patients with Parkinson's disease and pathological gambling. 1972 1

Few studies have investigated the relation between dream features and cognition in Parkinson's disease (PD), although vivid dreams, hallucinations and cognitive decline have been proposed as successive steps of a pathological continuum. Our objectives were therefore to characterize the dreams of early stage PD and to study the relation between dream characteristics, cognitive function, motor status, depression, dopaminergic treatment, and the presence of REM sleep behaviour disorder (RBD) and hallucinations. Dreams of 19 male PD patients and 21 matched control subjects were classified according to Hall and van de Castle system. h statistics was used to compare the dream content between patients and controls. We tested the relation between patients' dreams characteristics and cognitive function (Frontal assessment battery (FAB) and Mini-Mental State Examination tests) depression (Beck depression inventory), motor function (UPDRS), dopaminergic treatment, the presence of RBD (according to clinical criteria) and hallucinations, using general linear model statistics. Patients and controls differed only on FAB scores. Relevant differences in the Hall and van de Castle scale were found between patient's dreams and those of the control group, regarding animals, aggression/friendliness, physical aggression, befriender (higher in the patient group) and aggressor and bodily misfortunes (lower in the patient group) features. Cognitive and particularly frontal dysfunction had a significant influence on the frequency of physical aggression and animal related features, while dopaminergic doses, depressive symptoms, hallucinations and RBD did not. We found a pattern of dream alteration characterized by heightened aggressiveness and the presence of animals. These were related to more severe frontal dysfunction, which could be the origin of such changes.
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PMID:Dream features in the early stages of Parkinson's disease. 2171 20


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