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)

Parkinson's disease (PD) is the most common cause of disability in the elderly. It is currently recognized as a cause of secondary osteoporosis. To evaluate the prevalence of osteoporosis in PD and detect its risk factors, 52 patients with PD (36 men/16 women) and 52 controls paired for age and sex were recruited. Clinical data including demography, disease duration and disease severity were collected. All subjects had bone mineral density (BMD) measured by dual energy X-ray absorptiometry, dorsal and lumbar spine X-ray, and biological exams (osteocalcin, CTX, parathormon). The mean age of the patients was 60.0 +/- 9.25 years [30-77], and the mean disease duration was 4.9 +/- 4.5 years [0.2-17]. Nine patients (17.3%) were osteoporotic and 28 (53.8%) osteopenic. BMD at the lumbar spine and the hip was lower among patients than controls (spine: 1.031 vs. 1.175 g/cm(2); P < 0.001; hip: 0.968 vs. 1.054; P = 0.02). PD patients with low BMD presented a more severe disease and an insufficient sun exposure and calcium intake. There was a positive statistically significant correlation between patients BMD and body mass index and negative correlation with age, severity of PD, and osteocalcin levels. The prevalence of osteoporosis/osteopenia is high in PD patients and seems related to the severity of the disease, an insufficient sun exposure and calcium intake. This osteoporosis constitutes with falls the major risk factors of fracture in PD patients.
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PMID:Prevalence and risk factors of osteoporosis in patients with Parkinson's disease. 1859 45

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with selective loss of dopaminergic neurons in substantia nigra pars compacta. Among the proposed mechanisms of dopaminergic degeneration, oxidative stress is believed to play an important role. On the other hand, L-DOPA used as the main medication in PD and overproduction of dopamine (DA) in striatal neurons could elicit toxic effects due to formation of free radicals (FRs). Adenosine, an endogenous neuromodulator was shown in various experimental models to have neuroprotective properties. In our study, we investigated the role of adenosine A(1) and A(2A) receptor ligands in hydroxyl radical generation by L-DOPA in the rat striatum. The hydroxyl radical was assayed by HPLC-ED as a product of its reaction with p-hydroxybenzoic acid (PBA). Intrastriatal infusion of L-DOPA(50 microM) markedly increased dialysate level of DA and 3,4-dihydroxybenzoic acid (3,4-DHBA). An adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA, 25-50 microM), nonselectiveA(1)/A(2A) receptor agonist 2-chloroadenosine (2-CADO, 50-100 microM), and selective A(2A) receptor agonist CGS 21680 (25-50 microM) decreased the level of 3,4-DHBA. A non-selective A(1)/A(2A) adenosine receptor antagonist caffeine (100 microM) produced similar effect on 3,4-DHBA level. At the same time, CPA and 2-CADO, but not CGS 21680 or caffeine, decreased L-DOPA-induced DA release. The adenosine receptor ligands alone only weakly changed extracellular DA level and did not influence hydroxyl radical production. However, they showed scavenging activity in Fenton reaction in vitro. The primary caffeine metabolite in rodents, 1,3,7-trimethyl uric acid (1,3,7-mUA) decreased both, DA synthesis and 3,4-DHBA level. Thus, paradoxically, both agonists of A(1) receptor and agonist of A(2A) receptor as well as antagonist of A(1) and A(2A) receptors (caffeine), all decreased generation of FRs. Our study suggests that a decrease in hydroxyl radical generation caused by adenosine receptor ligands results from attenuation of L-DOPA-induced DA release or from their scavenging activity.
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PMID:Paradoxical effects of adenosine receptor ligands on hydroxyl radical generation by L-DOPA in the rat striatum. 1862 56

We investigated whether homocysteine (Hcy)- lowering therapy or an antioxidant prevented bone loss in Parkinson's disease (PD) patients taking levodopa. Forty-two PD patients with low bone mineral density (BMD) taking levodopa were randomly assigned to Hcy-lowering therapy (5 mg folate and 1500 microg vitamin B(12) daily), alpha-lipoic acid (alpha-LA) therapy (1200 mg daily), or control groups. Primary outcomes were BMD changes from baseline to 12 months. Secondary outcomes were changes in Hcy level, and C-telopeptide (CTX) levels at 12 months. Forty-one patients completed the study. Hcy-lowering therapy resulted in significantly greater BMD changes at the lumbar spine (4.4%), total femur (2.8%), and femur shaft (2.8%) than control (P = 0.005-0.023). BMD changes in the alpha-LA therapy group were similar to those of the control group, but changes at the trochanter (4.6%) were significantly greater in the alpha-LA therapy group than in the control group after adjustment for body mass index changes. Hcy concentrations decreased to 35.2% +/- 13.4% in the Hcy-lowering therapy group, but increased in other groups. Serum CTX levels at 12 months tended to be lower in the Hcy-lowering group (0.442 +/- 0.024 ng/mL) than control group (0.628 +/- 0.039 ng/mL) (P = 0.159). This small trial suggests that Hcy-lowering therapy may prevent bone loss in PD patients taking levodopa.
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PMID:Homocysteine-lowering therapy or antioxidant therapy for bone loss in Parkinson's disease. 1993 51

Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson's disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG.
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PMID:A biophysical model of the cortex-basal ganglia-thalamus network in the 6-OHDA lesioned rat model of Parkinson's disease. 2686 34

The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion-induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN-MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion-induced changes to CTX-MSN D1, CTX-MSN D2, TA-MSN, and MSN-MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function.
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PMID:Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model. 2810 25

Dynamical phenomena in the postural chain occur before, during and after the voluntary movement. These phenomena correspond to anticipatory (APA), simultaneous (SPA), and consecutive (CPA) postural adjustments, respectively. APA and, more recently, CPA, have been extensively investigated in the literature. SPA have surprisingly received much less attention. The aim of the present study was to examine the role(s) of SPA associated with a single step task (SST). Ten healthy young adults performed series of SST on a force-plate. A 2-DOF mechanical model was used to separate the dynamics of the swing leg and the dynamics of the rest of the body, corresponding to the focal and the postural component of the SST, respectively. The postural component was plotted against the focal one during SPA (from heel-off to foot-contact), and this plot was modelled as a Lissajous ellipse. Result showed that this ellipse systematically ran through the same three quadrants of the diagram. For each of these quadrants, the role of the postural component in regards to the focal one was interpreted according to the relative orientation of the postural and focal dynamics. Results thus showed that SPA ensured the following successive roles: counter-perturbation of swing leg dynamics following heel-off, propulsion of swing leg, counter-perturbation of swing leg dynamics again, and then braking swing leg movement. These new findings contribute to a better knowledge of postural adjustments properties, and may provide new insights for understanding balance troubles with aging and in neurological patients (e.g. people with Parkinson's disease).
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PMID:The role(s) of "Simultaneous Postural Adjustments" (SPA) during Single Step revealed with the Lissajous method. 3263 15