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)

It is not known if aging induces changes in nigral vascularization and nigral vascular endothelial growth factor (VEGF) levels similar to those previously reported for Parkinson's disease (PD). In this study nonexercised rats displayed age-dependent decreases in the density of nigral microvessels and VEGF mRNA expression, which were reversed by physical exercise. Such changes may enhance the vulnerability of dopaminergic neurons and the risk of developing PD, and may be reduced by exercise. Furthermore, the observed pattern is the opposite of that previously observed in PD, suggesting that the process underlying PD is not an accelerated age-dependent decline in the dopaminergic system.
J Cereb Blood Flow Metab 2009 Feb
PMID:Aging and sedentarism decrease vascularization and VEGF levels in the rat substantia nigra. Implications for Parkinson's disease. 1895 89

Smoking is associated with a lower incidence of Parkinson's disease (PD), which might be related to a neuroprotective action of nicotine. Postmortem studies have shown a decrease of cerebral nicotinic acetylcholine receptors (nAChRs) in PD. In this study, we evaluated the decrease of nAChRs in PD in vivo using positron emission tomography (PET), and we explored the relationship between nAChRs density and PD severity using both clinical scores and the measurement of striatal dopaminergic function. Thirteen nondemented patients with PD underwent two PET scans, one with 6-[(18)F]fluoro-3,4-dihydroxy-L-phenylalanine (6-[(18)F]fluoro-L-DOPA) to measure the dopaminergic function and another with 2-[(18)F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine (2-[(18)F]fluoro-A-85380), a radiotracer with high affinity for the nAChRs. Distribution volumes (DVs) of 2-[(18)F]fluoro-A-85380 measured in the PD group were compared with those obtained from six nonsmoking healthy controls, with regions-of-interest and voxel-based approaches. Both analyses showed a significant (P <0.05) decrease of 2-[(18)F]fluoro-A-85380 DV in the striatum (-10%) and substantia nigra (-14.9%) in PD patients. Despite the wide range of PD stages, no correlation was found between DV and the clinical and PET markers of PD severity.
J Cereb Blood Flow Metab 2009 Sep
PMID:Decrease of nicotinic receptors in the nigrostriatal system in Parkinson's disease. 1949 21

Deep brain stimulation (DBS) represents a major advance in the treatment of various severe movement disorders or neuropsychiatric diseases. Our understanding of the mechanism of action of this surgical treatment has greatly benefited from functional imaging studies. Most of these studies have been conducted in patients with Parkinson's disease (PD) treated by bilateral subthalamic nucleus (STN) stimulation. These studies have notably underlined the fact that STN stimulation influences motor, limbic, or associative cortical-subcortical loops in various (sometimes contradictory) ways. We present an up-to-date review of the information provided by functional imaging studies in surgery for PD, dystonia, tremor, as well as in psychiatric disorders such as depression or obsessive-compulsive disorder. On the basis of this information, proposed mechanisms of action of DBS are discussed, as well as the need for additional approaches such as improved anatomical localization of the contact used for stimulation or a better understanding of the electrical distribution around the electrode.
J Cereb Blood Flow Metab 2009 Nov
PMID:PET functional imaging of deep brain stimulation in movement disorders and psychiatry. 1965 84

Parkinson's disease (PD) is characterized by striatal dopamine depletion, especially in the posterior putamen. The dense connectivity profile of the striatum suggests that these local impairments may propagate throughout the whole cortico-striatal network. Here we test the effect of striatal dopamine depletion on cortico-striatal network properties by comparing the functional connectivity profile of the posterior putamen, the anterior putamen, and the caudate nucleus between 41 PD patients and 36 matched controls. We used multiple regression analyses of resting-state functional magnetic resonance imaging data to quantify functional connectivity across different networks. Each region had a distinct connectivity profile that was similarly expressed in patients and controls: the posterior putamen was uniquely coupled to cortical motor areas, the anterior putamen to the pre-supplementary motor area and anterior cingulate cortex, and the caudate nucleus to the dorsal prefrontal cortex. Differences between groups were specific to the putamen: although PD patients showed decreased coupling between the posterior putamen and the inferior parietal cortex, this region showed increased functional connectivity with the anterior putamen. We conclude that dopamine depletion in PD leads to a remapping of cerebral connectivity that reduces the spatial segregation between different cortico-striatal loops. These alterations of network properties may underlie abnormal sensorimotor integration in PD.
Cereb Cortex 2010 May
PMID:Spatial remapping of cortico-striatal connectivity in Parkinson's disease. 1971 Mar 57

We studied the time course and nature of interactions between the subthalamic nucleus (STN) and the motor cortex in 8 Parkinson disease (PD) patients with chronically implanted STN deep-brain stimulation (DBS) electrodes. We first identified the cortical evoked potentials following STN stimulation. The most consistent potential was positive wave with peak latency of 22.2 +/- 1.2 ms from stimulation of clinically effective contacts. We then stimulated the motor cortex with transcranial magnetic stimulation (TMS) at 2-15 ms and at the latency of the evoked potential ( approximately 23 ms) following STN DBS. TMS induced currents in 3 directions: lateral-medial (LM) direction activated corticospinal axons directly, posterior-anterior (PA), and anterior-posterior (AP) directions activated corticospinal neurons transynaptically. Motor-evoked potentials (MEP) elicited by AP and PA TMS were facilitated at short (2-4 ms) and medium latencies (21-24 ms). However, MEPs elicited by LM TMS were not modified by STN DBS. Short-latency antidromic stimulation of the corticosubthalamic projections and medium latency transmission likely through the basal ganglia-thalamocortical circuit led to cortical evoked potentials and increased motor cortex excitability at specific intervals following STN stimulation at clinically effective contacts. Cortical activation may be related to the clinical effects of STN DBS in PD.
Cereb Cortex 2010 Aug
PMID:The nature and time course of cortical activation following subthalamic stimulation in Parkinson's disease. 2001 46

We investigated abnormal premotor to motor (PMd-to-M1) connectivity in Parkinson's disease (PD) with repetitive transcranial magnetic stimulation (rTMS). We studied 28 patients off and on dopaminergic therapy and 28 healthy subjects. We delivered 5 Hz rTMS over M1 before and after conditioning PMd with 5 Hz rTMS. In healthy subjects, motor-evoked potentials (MEPs) elicited by M1-rTMS were facilitated and PMd-rTMS left MEPs unchanged. In patients, before PMd-rTMS, M1-rTMS induced no MEP facilitation, whereas after PMd-rTMS, it significantly facilitated MEPs only when patients were on therapy. In the second experiment, we delivered M1-rTMS under 3 different attention-demanding tasks: eyes closed, attention directed to the stimulated hand, and attention directed to the nonstimulated hand. In healthy subjects, a more pronounced MEP facilitation was present when subjects directed attention to the stimulated hand. In patients, the MEP facilitation was present when attention was directed to the stimulated hand only when patients were on therapy. Finally, we delivered M1-rTMS in patients on therapy while they were looking at the stimulated hand, before and after 1 Hz PMd-rTMS. PMd-rTMS reduced the attention-induced MEP facilitation. We conclude that in addition to abnormal M1 plasticity, the reduced MEP facilitation in PD also reflects altered PMd-to-M1 connectivity.
Cereb Cortex 2010 Sep
PMID:Dopamine influences primary motor cortex plasticity and dorsal premotor-to-motor connectivity in Parkinson's disease. 2005 62

Parkinson's disease (PD) is associated with elevated expression of a specific disease-related spatial covariance pattern (PDRP) in radiotracer scans of cerebral blood flow and metabolism. In this study, we scanned nine early-stage patients with PD and nine healthy controls using continuous arterial spin labeling (CASL) perfusion magnetic resonance imaging (pMRI). Parkinson's disease-related metabolic pattern expression in CASL pMRI scans was compared with the corresponding (18)F-fluorodeoxyglucose positron emission tomography values. The PDRP expression was abnormally elevated (P<0.01) in patients scanned with either modality, and the two values were highly intercorrelated (P<0.0001). Perfusion MRI methods can be used for accurate quantification of disease-related covariance patterns.
J Cereb Blood Flow Metab 2010 Mar
PMID:Parkinson's disease spatial covariance pattern: noninvasive quantification with perfusion MRI. 2005 75

Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if decortication reverses or prevents dopamine depletion-induced spine loss by placing motor cortex lesions 4 weeks after, or at the time of, 6-hydroxydopamine lesions of the SN. Animals were sacrificed 4 weeks after cortical lesions. Motor cortex lesions significantly reversed the loss of MSN spines elicited by dopamine denervation; a similar effect was observed in the prevention experiment. We then determined if modulating glutamate release in organotypic cocultures prevented spine loss. Treatment of the cultures with the mGluR2/3 agonist LY379268 to suppress corticostriatal glutamate release completely blocked spine loss in dopamine-denervated cultures. These studies provide the first evidence to show that MSN spine loss associated with parkinsonism can be reversed and point to suppression of corticostriatal glutamate release as a means of slowing progression in Parkinson's disease.
Cereb Cortex 2010 Oct
PMID:Cortical regulation of striatal medium spiny neuron dendritic remodeling in parkinsonism: modulation of glutamate release reverses dopamine depletion-induced dendritic spine loss. 2011 84

Assays of mitochondrial electron transport system (ETS) activity in circulating blood platelets have been used to investigate the cause of neurodegenerative diseases. However, the correspondence between platelet ETS function and cerebral mitochondrial metabolism is not well characterized. To assess the validity of using platelet ETS activity to infer cerebral mitochondrial metabolism, we measured platelet ETS activity (complex I and complex I+III), cerebral metabolic rate of oxygen (CMRO(2)), and the CMRO(2)/cerebral metabolic rate for glucose ratio in 40 subjects: 7 with never-medicated Parkinson's disease, 13 with genetically proved Huntington's disease, and 20 normal controls. We found no correlation between in vivo measures of cerebral mitochondrial oxidative metabolism and ex vivo assays of platelet complex I and complex I+III activity performed on blood collected immediately before cerebral metabolism studies. We saw no evidence of a threshold effect when comparing platelet complex I and complex I+III activity with cerebral oxidative metabolism across a 4- to 10-fold range of platelet ETS activity. On the basis of these data, we conclude that measures of mitochondrial complex I and I+III activity in platelets within the ranges we have studied do not correlate with oxidative function of cerebral mitochondria.
J Cereb Blood Flow Metab 2011 Jan
PMID:Platelet mitochondrial complex I and I+III activities do not correlate with cerebral mitochondrial oxidative metabolism. 2095 51

Olfactory impairment is a consistent premotor symptom in sporadic Parkinson's disease (PD), presumably caused by pathological processes in the olfactory bulb and olfactory structures within mesolimbic brain areas. The objective of the present study was to obtain an in-depth insight into olfactory network dysfunction in PD patients. Event-related functional magnetic resonance imaging (3 T) was conducted with 16 early-stage PD patients and 16 matched controls during an odor detection task. Activation within the olfactory network was analyzed both in terms of strength of activation (whole-brain random effects, regions of interest [ROI] analysis based on the hemodynamic response function) as well as time-course characteristics (finite impulse response-based ROI analysis). Olfactory-induced activation in patients with PD in comparison to a standard activation pattern obtained from controls revealed profound hyperactivation in piriform and orbitofrontal cortices. However, whereas orbitofrontal areas seem to be unable to discriminate between signal and noise, primary olfactory cortex shows preserved discriminatory ability. These results support a complex network dysfunction that exceeds structural pathology observed in the olfactory bulb and mesolimbic cortices and thus demonstrate the important contribution of functional data to describe network dynamics occurring in the degenerating brain.
Cereb Cortex 2011 Jun
PMID:Altered activation patterns within the olfactory network in Parkinson's disease. 2104 84


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