scholarly journals Differential Changes in Postsynaptic Density Proteins in Postmortem Huntington’s Disease and Parkinson’s Disease Human Brains

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
C. Fourie ◽  
E. Kim ◽  
H. Waldvogel ◽  
J. M. Wong ◽  
A. McGregor ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Immunohistochemical Analysis ◽  
Synaptic Proteins ◽  
Postmortem Brain ◽  
Postmortem Brain Tissue ◽  
Human Brains

NMDA and AMPA-type glutamate receptors and their bound membrane-associated guanylate kinases (MAGUKs) are critical for synapse development and plasticity. We hypothesised that these proteins may play a role in the changes in synapse function that occur in Huntington’s disease (HD) and Parkinson’s disease (PD). We performed immunohistochemical analysis of human postmortem brain tissue to examine changes in the expression of SAP97, PSD-95, GluA2 and GluN1 in human control, and HD- and PD-affected hippocampus and striatum. Significant increases in SAP97 and PSD-95 were observed in the HD and PD hippocampus, and PSD95 was downregulated in HD striatum. We observed a significant increase in GluN1 in the HD hippocampus and a decrease in GluA2 in HD and PD striatum. Parallel immunohistochemistry experiments in the YAC128 mouse model of HD showed no change in the expression levels of these synaptic proteins. Our human data show that major but different changes occur in glutamatergic proteins in HD versus PD human brains. Moreover, the changes in human HD brains differ from those occurring in the YAC128 HD mouse model, suggesting that unique changes occur at a subcellular level in the HD human hippocampus.

scholarly journals Single-Cell RNA Sequencing in Parkinson’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 368
Author(s):  
Shi-Xun Ma ◽  
Su Bin Lim
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Cell ◽  
Rna Sequencing ◽  
Rna Degradation ◽  
Postmortem Brain ◽  
Cell Type ◽  
New Findings ◽  
Postmortem Brain Tissue ◽  
Technical Challenges

Single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have enhanced the understanding of the molecular pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). Nonetheless, their application in PD has been limited due mainly to the technical challenges resulting from the scarcity of postmortem brain tissue and low quality associated with RNA degradation. Despite such challenges, recent advances in animals and human in vitro models that recapitulate features of PD along with sequencing assays have fueled studies aiming to obtain an unbiased and global view of cellular composition and phenotype of PD at the single-cell resolution. Here, we reviewed recent sc/snRNA-seq efforts that have successfully characterized diverse cell-type populations and identified cell type-specific disease associations in PD. We also examined how these studies have employed computational and analytical tools to analyze and interpret the rich information derived from sc/snRNA-seq. Finally, we highlighted important limitations and emerging technologies for addressing key technical challenges currently limiting the integration of new findings into clinical practice.

Programming of single movements in Parkinson's disease: Comparison with huntington's disease

1992 ◽  
Vol 14 (5) ◽  
pp. 762-772 ◽  
Author(s):  
Dean L. Jones ◽  
James G. Phillips ◽  
John L. Bradshaw ◽  
Robert Iansek ◽  
Judy A. Bradshaw
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Huntington's Disease ◽  
Huntington’S Disease

Pyrethroid and organophosphate insecticide exposure in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease: an immunohistochemical analysis of tyrosine hydroxylase and glial fibrillary acidic protein in dorsolateral striatum

2009 ◽  
Vol 25 (1) ◽  
pp. 25-39 ◽  
Author(s):  
CA Dodd ◽  
BG Klein
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tyrosine Hydroxylase ◽  
Mouse Model ◽  
Glial Fibrillary Acidic Protein ◽  
Immunohistochemical Analysis ◽  
Acidic Protein ◽  
Nigrostriatal Pathway ◽  
Organophosphate Insecticide ◽  
Nigrostriatal Degeneration

The pyrethroid insecticide permethrin and the organophosphate insecticide chlorpyrifos can experimentally produce Parkinson’s disease (PD)-associated changes in the dopaminergic nigrostriatal pathway, short of frank degeneration, although at doses considerably higher than from a likely environmental exposure. The ability of permethrin (200 mg/kg), chlorpyrifos (50 mg/kg), or combined permethrin + chlorpyrifos to facilitate nigrostriatal damage in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg) C57BL/6 mouse model of PD was investigated in three separate experiments. Tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) immunohistochemistry assessed nigrostriatal degeneration or nigrostriatal damage more subtle than frank degeneration. Four fields in the dorsolateral caudate-putamen were examined at two rostrocaudal locations. The dopaminergic neurotoxin MPTP decreased striatal TH immunopositive neuropil and increased GFAP immunopositive neuropil. Neither permethrin nor chlorpyrifos, alone or in combination, altered the effects of MPTP upon TH or GFAP immunostaining. Permethrin alone increased striatal GFAP immunopositive neuropil but not when combined with chlorpyrifos treatment. Therefore, combined administration of the two insecticides appeared to protect against an increase in a neuropathological indicator of striatal damage seen with permethrin treatment alone. Differences compared with analysis of entire striatum emphasize the value of varying the topographic focus used to assess nigrostriatal degeneration in studies of insecticides in PD.

scholarly journals A Mobile Application for Smart Computer-Aided Self-Administered Testing of Cognition, Speech, and Motor Impairment

Sensors ◽  
2020 ◽  
Vol 20 (11) ◽  
pp. 3236 ◽  
Author(s):  
Andrius Lauraitis ◽  
Rytis Maskeliūnas ◽  
Robertas Damaševičius ◽  
Tomas Krilavičius
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Energy Expenditure ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mobile Application ◽  
Speech Analysis ◽  
Finger Tapping ◽  
Hand Tremor ◽  
Neural Impairment

We present a model for digital neural impairment screening and self-assessment, which can evaluate cognitive and motor deficits for patients with symptoms of central nervous system (CNS) disorders, such as mild cognitive impairment (MCI), Parkinson’s disease (PD), Huntington’s disease (HD), or dementia. The data was collected with an Android mobile application that can track cognitive, hand tremor, energy expenditure, and speech features of subjects. We extracted 238 features as the model inputs using 16 tasks, 12 of them were based on a self-administered cognitive testing (SAGE) methodology and others used finger tapping and voice features acquired from the sensors of a smart mobile device (smartphone or tablet). Fifteen subjects were involved in the investigation: 7 patients with neurological disorders (1 with Parkinson’s disease, 3 with Huntington’s disease, 1 with early dementia, 1 with cerebral palsy, 1 post-stroke) and 8 healthy subjects. The finger tapping, SAGE, energy expenditure, and speech analysis features were used for neural impairment evaluations. The best results were achieved using a fusion of 13 classifiers for combined finger tapping and SAGE features (96.12% accuracy), and using bidirectional long short-term memory (BiLSTM) (94.29% accuracy) for speech analysis features.

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