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 two commonest, clinically well-defined, forms of parkinsonism are idiopathic Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Both involve, inter alia, pathological changes in the substantia nigra pars compacta (SN(C)). In PD there is neuronal loss with associated Lewy body pathology and microglial activation. Three morphological features have been identified [Brain 114 (1991), 2283; Greenfield's Neuropathology 2 (1997), 289]. First, there is a gradient of pathological change such that the lateral segments are more affected than the medial. Second, there is thinning of the pigmented tissue, and third, there is a broadening of the overall structure in a dorsal-ventral direction, possibly caused by the migration of melanin-laden macrophages [Greenfield's Neuropathology 2 (1997), 289]. In contrast, PSP is characterized pathologically by intraneuronal neurofibrillary tangles. There are two morphological features in the SN(C) [Brain 114 (1991), 2283]. First, the gradient of pathological change is in the opposite direction to that of PD (i.e., the medial segments are more affected than the lateral). Second, there is atrophy. Any technique sensitive to neuropathology should be capable of detecting these features. We have previously reported on a new approach to detecting signal change in the substantia nigra in PD. This makes use of a ratio of images acquired by two distinct inversion recovery sequences [J. Neurol, Neurosurg. Psychiatry 67 (1999), 815; Am. J. Neuroradiol. 21 (2000) 697]. The prior work suggests that the technique is sensitive to, but not necessarily specific for, PD. We present here a preliminary report on an extension of the work. This is a semiautomated segmentation analysis that enables the substantia nigra to be displayed as an isolated structure. The technique is now given the acronym SIRRIM (segmented inversion recovery ratio imaging). In contrast to our earlier work, it allows for a more accurate assessment of the gross abnormalities. We report typical SIRRIM images of the SN(C). Images are shown for three subjects: a normal control, a patient with PD, and a "disease control" (a patient with PSP). In these examples all three morphological features of PD, as well as both morphological features of PSP, have radiological correlates. These preliminary findings suggest that SIRRIM may be specific for both diseases.
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PMID:MRI correlates of pathology in parkinsonism: segmented inversion recovery ratio imaging (SIRRIM). 1464

To elucidate MR imaging changes of the substantia innominata in Parkinson's disease (PD), using a 1.5-T superconductive MR unit, the thickness of the substantia innominata was measured on coronal thin-section images in 44 PD patients and 20 age-matched control subjects. We also evaluated the correlation between the thickness of the substantia innominata and mental status in PD patients. Mean thickness of the substantia innominata was 2.3 mm in PD patients, and 2.5 mm in control subjects. Thinning of the substantia innominata was statistically significant in PD patients compared with control subjects, although there were large overlaps. Among the PD patients, thinning was remarkable in cases with dementia. A positive correlation between thickness of substantia innominata and score of Mini-Mental-Status-Examination was also observed in PD patients. Atrophy of the substantia innominata was demonstrated, especially in PD patients with cognitive impairment, on coronal MR images, and this is compatible with the previous pathological reports.
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PMID:Substantia innominata: MR findings in Parkinson's disease. 1531 99

Alpha-synuclein (alpha-Syn) fibrils are the major component of Lewy bodies that are closely associated with the pathogenesis of Parkinson's disease, but the mechanism for the fibril assembly remains poorly understood. Here we report using a combination of peptide truncation and atomic force microscopy (AFM) to elucidate the self-assembly and morphology of the alpha-Syn fibrils. The results show that protease K significantly slims the fibrils from the mean height of approximately 6.6 to approximately 4.7 nm, whereas chaotropic denaturant urea completely breaks down the fibrils into small particles. The in situ enzymatic digestion also results in thinning of the fibrils, giving rise to some nicks on the fibrils. Moreover, N- or C-terminally truncated alpha-Syn fragments assemble into thinner filaments with the heights depending on the peptide lengths. A nine-residue peptide corresponding to the homologous GAV-motif sequence can form very thin (approximately 2.2 nm) but long (>1 microm) filaments. Thus, the central sequence of alpha-Syn forms a fibrillar core by cross-beta-structure that is flanked by two flexible termini, and the orientation of the fibril growth is perpendicular to the beta-sheet structures.
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PMID:Assembly of alpha-synuclein fibrils in nanoscale studied by peptide truncation and AFM. 1823 Mar 46

Bone marrow stromal cells are multipotential cells that can be induced to differentiate into osteoblasts, chondrocytes, myocytes and adipocytes in different microenvironments. Recent studies revealed that bone marrow stromal cells could improve neurological deficits of various damages or diseases of the central nervous system such as Parkinson's disease, brain trauma, spinal cord injury and multiple sclerosis, and promote glia-axonal remodeling in animal brain subjected to an experimentally induced stroke. In the present study, bone marrow stromal cells were intracerebrally transplanted into the cerebrum following a transient middle cerebral artery occlusion. Our aim was to find out whether the bone marrow stromal cells could survive and express neural phenotypic proteins and, in addition, whether they could restore the behavioral and functional deficits of the cerebral ischemic rats. Our results demonstrated that transplanted bone marrow stromal cells survived and migrated to areas around the lesion site. Some of them exhibited marker proteins of astrocytes and oligodendrocytes. Bone marrow stromal cell implantation significantly reduced the transient middle cerebral artery occlusion-induced cortical loss and thinning of the white matter and enhanced cortical beta-III-tubulin immunoreactivity. Rats implanted with bone marrow stromal cells showed significant improvement in their performance of elevated body swing test and forelimb footprint analysis and only transient recovery of the adhesive-removal test. Our data support bone marrow stromal cells as a valuable source of autologous or allogenic donor cells for transplantation to improve the outcome following cerebral ischemia.
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PMID:Transplanted bone marrow stromal cells migrate, differentiate and improve motor function in rats with experimentally induced cerebral stroke. 1864 94

The pathology of Parkinson's disease (PD) is not confined to the brainstem regions, but spreads to involve the neocortical areas. Using surface-based cortical thickness analysis, we studied the topographical distribution of cortical thinning in nondemented patients with mild PD. The high-resolution magnetic resonance imaging (MRI) studies were performed in 48 patients with PD without dementia and 56 age-matched healthy controls. Using the Freesurfer software, surface-based analysis was done to find changes in cerebral cortical thickness in patients with PD. Compared to the controls, patients with PD showed significant cortical thinning in the temporal, inferior parietal, rostral frontal, and orbitofrontal cortical areas. Thinning of the cerebral cortex occurs even in nondemented patients with mild PD, and its topographical distribution was similar to that of the neocortical Lewy bodies. Further studies are needed to find pathological and clinical correlates of thinned cerebral cortex found in nondemented patients with mild PD.
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PMID:Topographical distribution of cerebral cortical thinning in patients with mild Parkinson's disease without dementia. 2010 69

Animal data indicate that the recreational drug ecstasy (3,4-methylenedioxymethamphetamine) can damage brain serotonin neurons. However, human neuroimaging measurements of serotonin transporter binding, a serotonin neuron marker, remain contradictory, especially regarding brain areas affected; and the possibility that structural brain differences might account for serotonin transporter binding changes has not been explored. We measured brain serotonin transporter binding using [(11)C] N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine in 50 control subjects and in 49 chronic (mean 4 years) ecstasy users (typically one to two tablets bi-monthly) withdrawn from the drug (mean 45 days). A magnetic resonance image for positron emission tomography image co-registration and structural analyses was acquired. Hair toxicology confirmed group allocation but also indicated use of other psychoactive drugs in most users. Serotonin transporter binding in ecstasy users was significantly decreased throughout all cerebral cortices (range -19 to -46%) and hippocampus (-21%) and related to the extent of drug use (years, maximum dose), but was normal in basal ganglia and midbrain. Substantial overlap was observed between control and user values except for insular cortex, in which 51% of ecstasy user values fell below the lower limit of the control range. Voxel-based analyses confirmed a caudorostral gradient of cortical serotonin transporter binding loss with occipital cortex most severely affected. Magnetic resonance image measurement revealed no overall regional volume differences between groups; however, a slight left-hemispheric biased cortical thinning was detected in methamphetamine-using ecstasy users. The serotonin transporter binding loss was not related to structural changes or partial volume effect, use of other stimulant drugs, blood testosterone or oestradiol levels, major serotonin transporter gene promoter polymorphisms, gender, psychiatric status, or self-reported hyperthermia or tolerance. The ecstasy group, although 'grossly behaviourally normal', reported subnormal mood and demonstrated generally modest deficits on some tests of attention, executive function and memory, with the latter associated with serotonin transporter decrease. Our findings suggest that the 'typical'/low dose (one to two tablets/session) chronic ecstasy-polydrug user might display a highly selective mild to marked loss of serotonin transporter in cerebral cortex/hippocampus in the range of that observed in Parkinson's disease, which is not gender-specific or completely accounted for by structural brain changes, recent use of other drugs (as assessed by hair analyses) or other potential confounds that we could address. The striking sparing of serotonin transporter-rich striatum (although possibly affected in 'heavier' users) suggests that serotonergic neurons innervating cerebral cortex are more susceptible, for unknown reasons, to ecstasy than those innervating subcortical regions and that behavioural problems in some ecstasy users during abstinence might be related to serotonin transporter changes limited to cortical regions.
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PMID:Decreased cerebral cortical serotonin transporter binding in ecstasy users: a positron emission tomography/[(11)C]DASB and structural brain imaging study. 2048 17

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder diagnosed on the basis of motor symptoms, but that also includes cognitive and visuo-spatial deficits. Though PD is known to initially affect subcortical regions, the cortex also exhibits neuronal loss in the course of the disease as post mortem studies have shown. So far, PD-related pattern of cortical damage remains unclear, because of disease-caused heterogeneity, and also in part because of methodological issues such as the limitations of Voxel Based Morphometry. Here corticometry was used, a technique that decouples local surface from thickness, to obtain a better picture of PD corticomorphometric patterns. We acquired MRI volumes for 33 healthy controls (HC) and 49 PD patients, extracted local cortical thickness and surface area and modeled both of them as a function of group and age for each participant. Cortical thickness averaged on the whole cortex did not differ between the two groups while mean surface area was significantly larger in the PD group. The bilateral parietal lobule, the right superior frontal gyrus, the left cingulate cortex and the left insular cortex exhibited larger local surface area in the PD group. The right precuneus exhibited cortical thinning associated with age in the PD group and not in the HC group. Furthermore, cortical thinning was observed in the PD group compared with the control group in the left medial supplementary motor area (SMA) and in the right dorsal pre-SMA. Finally, we found the left temporal pole thickness to correlate with disease duration, as well as the bilateral occipital cortex and Broca's area. These results suggest that PD etiology is associated with specific cortical alterations, which could account for cognitive deficits that arise as the disease evolves. Finally, our results observed in the occipital cortex as a function of disease duration may indicate the increase in PD-related visuo-spatial deficits, which can sometimes result in hallucinations later on in the disease. In the future, MRI-generated corticometry, combined with additional behavioral markers, may prove to be a useful diagnosis tool to characterize the evolution of motor and cognitive deficits in PD.
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PMID:Patterns of cortical thickness and surface area in early Parkinson's disease. 2118 30

Establishing the neurological basis of behavioural dysfunction is key to provide a better understanding of Parkinson's disease (PD) and facilitate development of effective novel therapies. For this, the relationships between longitudinal structural brain changes associated with motor behaviour were determined in a rat model of PD and validated by post-mortem immunohistochemistry. Rats bearing a nigrostriatal lesion induced by infusion of the proteasome inhibitor lactacystin into the left-medial forebrain bundle and saline-injected controls underwent magnetic resonance imaging (MRI) at baseline (prior to surgery) and 1, 3 and 5 weeks post-surgery with concomitant motor assessments consisting of forelimb grip strength, accelerating rotarod, and apormorphine-induced rotation. Lactacystin-injected rats developed early motor deficits alongside decreased ipsilateral cortical volumes, specifically thinning of the primary motor (M1) and somatosensory cortices and lateral ventricle hypertrophy (as determined by manual segmentation and deformation-based morphometry). Although sustained, motor dysfunction and nigrostriatal damage were maximal by 1 week post-surgery. Additional volume decreases in the ipsilateral ventral midbrain; corpus striatum and thalamus were only evident by week 3 and 5. Whilst cortical MRI volume changes best predicted the degree of motor impairment, post-mortem tyrosine hydroxylase immunoreactivity in the striatum was a better predictor of motor behaviour overall, with the notable exception of performance in the accelerating rotarod, in which, M1 cortical thickness remained the best predictor. These results highlight the importance of identifying extra-nigral regions of damage that impact on behavioural dysfunction from damage to the nigrostriatal system.
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PMID:Evolution of extra-nigral damage predicts behavioural deficits in a rat proteasome inhibitor model of Parkinson's disease. 2136 87

Neurodegeneration in clinically manifest Parkinson's disease affects the substantia nigra pars compacta, and gradually spreads to the limbic cortices and the neocortex. We used MRI imaging coupled with automated surface reconstruction and segmentation methods to examine cortical thickness and subcortical volumes in nondemented, early-stage Parkinson's disease patients compared to matched healthy control participants. These methods, which have been previously used to document cortical thickness changes in patients with Alzheimer's disease and Huntington's disease but not Parkinson's disease, use MR signal intensity information and the geometric constraints of the cortical and subcortical structures for an accurate tissue classification. Parkinson's disease patients were matched to the control group in psychomotor processing speed and executive functioning, but showed higher anxiety state scores. Our results demonstrated focal cortical thinning in the Parkinson's disease group in the orbitofrontal cortex, ventrolateral prefrontal cortex, and occipito-parietal areas. Subcortically, striatal volume loss was noted. These results demonstrate that both cortical and subcortical structural changes occur at relatively early stages of the disease, and are discussed in terms of the emotional dysregulation that occurs early on in patients with Parkinson's disease.
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PMID:Focal cortical and subcortical atrophy in early Parkinson's disease. 2146 59

The pathology of Parkinson's disease (PD) is not confined to the nigrostriatal dopaminergic pathway, but also involves widespread cerebral cortical areas. Such non-nigrostriatal lesions may contribute to disabling dopa-resistant parkinsonian motor deficits. We performed cortical thickness analysis to identify cerebral cortical brain areas in which thickness correlates with the severity of parkinsonian motor deficits. We performed T1-weighted brain magnetic resonance imaging studies in 142 PD patients. Motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS) were measured, and subscores were calculated for bradykinesia, rigidity, tremor, and axial motor deficits. Using FreeSurfer software, we studied cortical areas in which thickness correlates with disease duration or the severity of parkinsonian motor deficits. The cortical thickness of the parieto-temporal association cortex, including the inferior parietal and posterior parietal cortices, showed a negative correlation with disease duration, total UPDRS motor score, and UPDRS subscores for bradykinesia and axial motor deficits. We found no cortical areas in which thickness correlated with subscores for tremor and rigidity. In addition to nigrostriatal dopaminergic deficit, progressive thinning of the parieto-temporal sensory association cortices related to disease duration seems to be related in part to the exacerbation of bradykinesia and the axial motor symptoms of PD.
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PMID:Cerebral cortical areas in which thickness correlates with severity of motor deficits of Parkinson's disease. 2151 41


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