scholarly journals Microglia Implicated in Tauopathy in the Striatum of Neurodegenerative Disease Patients from Genotype to Phenotype

2020 ◽  
Vol 21 (17) ◽  
pp. 6047
Author(s):  
Huifangjie Li ◽  
William C. Knight ◽  
Pengfei Yang ◽  
Yingqiu Guo ◽  
Joel S. Perlmutter ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oxidative Damage ◽  
Lewy Body ◽  
Dopamine Metabolism ◽  
Tau Proteins ◽  
Translocator Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Microglial Phenotype ◽  
Tau Fibrils

We found interactions between dopamine and oxidative damage in the striatum involved in advanced neurodegeneration, which probably change the microglial phenotype. We observed possible microglia dystrophy in the striatum of neurodegenerative brains. To investigate the interactions between oxidative damage and microglial phenotype, we quantified myeloperoxidase (MPO), poly (ADP-Ribose) (PAR), and triggering receptors expressed on myeloid cell 2 (TREM2) using enzyme-linked immunosorbent assay (ELISA). To test the correlations of microglia dystrophy and tauopathy, we quantified translocator protein (TSPO) and tau fibrils using autoradiography. We chose the caudate and putamen of Lewy body diseases (LBDs) (Parkinson’s disease, Parkinson’s disease dementia, and Dementia with Lewy body), Alzheimer’s disease (AD), and control brains and genotyped for TSPO, TREM2, and bridging integrator 1 (BIN1) genes using single nucleotide polymorphisms (SNP) assays. TREM2 gene variants were absent across all samples. However, associations between TSPO and BIN1 gene polymorphisms and TSPO, MPO, TREM2, and PAR level variations were found. PAR levels reduced significantly in the caudate of LBDs. TSPO density and tau fibrils decreased remarkably in the striatum of LBDs but increased in AD. Oxidative damage, induced by misfolded tau proteins and dopamine metabolism, causes microglia dystrophy or senescence during the late stage of LBDs. Consequently, microglia dysfunction conversely reduces tau propagation. The G allele of the BIN1 gene is a potential risk factor for tauopathy.

scholarly journals Protective Effects of an Ancient Chinese Kidney-Tonifying Formula against H2O2-Induced Oxidative Damage to MES23.5 Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Yihui Xu ◽  
Wei Lin ◽  
Shuifen Ye ◽  
Huajin Wang ◽  
Tingting Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oxidative Damage ◽  
Cell Damage ◽  
Critical Role ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Transmission Electron ◽  
Potential Strategy

Oxidative damage plays a critical role in the etiology of neurodegenerative disorders including Parkinson’s disease (PD). In our study, an ancient Chinese kidney-tonifying formula, which consists ofCistanche,Epimedii,andPolygonatum cirrhifolium, was investigated to protect MES23.5 dopaminergic neurons against hydrogen peroxide- (H2O2-) induced oxidative damage. The damage effects of H2O2on MES23.5 cells and the protective effects of KTF against oxidative stress were evaluated using MTT assay, transmission electron microscopy (TEM), immunocytochemistry (ICC), enzyme-linked immunosorbent assay (ELISA), and immunoblotting. The results showed that cell viability was dramatically decreased after a 12 h exposure to 150 μM H2O2. TEM observation found that the H2O2-treated MES23.5 cells presented cellular organelle damage. However, when cells were incubated with KTF (3.125, 6.25, and 12.5 μg/ml) for 24 h after H2O2exposure, a significant protective effect against H2O2-induced damage was observed in MES23.5 cells. Using ICC, we found that KTF inhibited the reduction of the tyrosine hydroxylase (TH) induced by H2O2, upregulated the mRNA and protein expression of HO-1, CAT, and GPx-1, and downregulated the expression of caspase 3. These results indicated that KTF may provide neuron protection against H2O2-induced cell damage through ameliorating oxidative stress, and our findings provide a new potential strategy for the prevention and treatment of Parkinson’s disease.

Neuroprotective Effects of a GLP-2 Analogue in the MPTP Parkinson’s Disease Mouse Model

2021 ◽  
pp. 1-15
Author(s):  
Zijuan Zhang ◽  
Li Hao ◽  
Ming Shi ◽  
Ziyang Yu ◽  
Simai Shao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Neurodegenerative Disorder ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Dual Agonist

Background: Glucagon-like peptide 2 (GLP-2) is a peptide hormone derived from the proglucagon gene expressed in the intestines, pancreas and brain. Some previous studies showed that GLP-2 improved aging and Alzheimer’s disease related memory impairments. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and to date, there is no particular medicine reversed PD symptoms effectively. Objective: The aim of this study was to evaluate neuroprotective effects of a GLP-2 analogue in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) PD mouse model. Methods: In the present study, the protease resistant Gly(2)-GLP-2 (50 nmol/kg ip.) analogue has been tested for 14 days by behavioral assessment, transmission electron microscope, immunofluorescence histochemistry, enzyme-linked immunosorbent assay and western blot in an acute PD mouse model induced by MPTP. For comparison, the incretin receptor dual agonist DA5-CH was tested in a separate group. Results: The GLP-2 analogue treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement imbalance of mice. Gly(2)-GLP-2 treatment also protected dopaminergic neurons and restored tyrosine hydroxylase expression levels in the substantia nigra. Gly(2)-GLP-2 furthermore reduced the inflammation response as seen in lower microglia activation, and decreased NLRP3 and interleukin-1β pro-inflammatory cytokine expression levels. In addition, the GLP-2 analogue improved MPTP-induced mitochondrial dysfunction in the substantia nigra. The protective effects were comparable to those of the dual agonist DA5-CH. Conclusion: The present results demonstrate that Gly(2)-GLP-2 can attenuate NLRP3 inflammasome-mediated inflammation and mitochondrial damage in the substantia nigra induced by MPTP, and Gly(2)-GLP-2 shows neuroprotective effects in this PD animal model.

scholarly journals Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy body diseases

2021 ◽  
Author(s):  
Rahel Feleke ◽  
Regina H. Reynolds ◽  
Amy M. Smith ◽  
Bension Tilley ◽  
Sarah A. Gagliano Taliun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Lewy Body ◽  
Molecular Mechanisms ◽  
Lewy Bodies ◽  
Subsequent Development ◽  
Lewy Body Dementia ◽  
Anterior Cingulate ◽  
Lewy Body Diseases

AbstractParkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms underlying PDD and DLB remain largely unknown, a knowledge gap that presents an impediment to the discovery of disease-modifying therapies. Transcriptomic profiling can contribute to addressing this gap, but remains limited in the LBDs. Here, we applied paired bulk-tissue and single-nucleus RNA-sequencing to anterior cingulate cortex samples derived from 28 individuals, including healthy controls, PD, PDD and DLB cases (n = 7 per group), to transcriptomically profile the LBDs. Using this approach, we (i) found transcriptional alterations in multiple cell types across the LBDs; (ii) discovered evidence for widespread dysregulation of RNA splicing, particularly in PDD and DLB; (iii) identified potential splicing factors, with links to other dementia-related neurodegenerative diseases, coordinating this dysregulation; and (iv) identified transcriptomic commonalities and distinctions between the LBDs that inform understanding of the relationships between these three clinical disorders. Together, these findings have important implications for the design of RNA-targeted therapies for these diseases and highlight a potential molecular “window” of therapeutic opportunity between the initial onset of PD and subsequent development of Lewy body dementia.

Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson's disease

2010 ◽  
Vol 1328 ◽  
pp. 139-151 ◽  
Author(s):  
Mohd.Moshahid Khan ◽  
Ajmal Ahmad ◽  
Tauheed Ishrat ◽  
M. Badruzzaman Khan ◽  
Md. Nasrul Hoda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oxidative Damage ◽  
Rat Model ◽  
Dopamine Depletion ◽  
6 Hydroxydopamine
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