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

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