Reactive astrogliosis in rats with LPS-induced Parkinson's disease

The astrogliosis was considered as a beneficial process to protect neurons and repair the tissue after CNS insult for a long time. However, numerous study indicate that under some specific conditions, reactive astrocytes can exacerbate neuroinflammation and tissue damage. Parkinson's disease (PD) is one of the most common neurodegenerative diseases that is a major medical and social problem. The progressive course of the disease requires continuous therapy, in the later stages it causes a disability of the patient, which entails the need for constant care and causes significant economic losses. The pathophysiological bases of CP remain unclear, making it impossible to diagnose the disease early, predict its course, and develop pathogenetic treatments. Neuroinflammation of polyetiological genesis, whose development involves micro- and astroglial cells, is considered to be a leading pathogenetic factor of CP. However, the functional state of astroglia in the conditions of development of this neuropathology remains the least studied. The aim of the study was to investigate the functional state of astroglia in rats with PD induced by bacterial lipopolysaccharide (LPS-PD). It has been established that the development of LPS-PD in rats is accompanied by reactive astrogliosis with overexpression of glial fibrillar acidic protein (GFAP) and products of its degradation by astrocytes of the hippocampal region of the brain. Overexpression of GFAP is associated with an increase in the level of myelin basic protein (MBP) in brain homogenates and a decrease in the level of neuronal NO synthase.

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Gene expression analysis in modeling Parkinson’s disease

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.04.103-104 ◽

2020 ◽

pp. 103-104

Author(s):

М.М. Руденок ◽

А.Х. Алиева ◽

А.А. Колачева ◽

М.В. Угрюмов ◽

П.А. Сломинский ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Stage ◽

Systemic Disease ◽

Molecular Genetic ◽

Presymptomatic Stage ◽

Whole Transcriptome Analysis ◽

Whole Transcriptome ◽

The Brain ◽

Transcriptome Level

Несмотря на очевидный прогресс, достигнутый в изучении молекулярно-генетических факторов и механизмов патогенеза болезни Паркинсона (БП), в настоящее время стало ясно, что нарушения в структуре ДНК не описывают весь спектр патологических изменений, наблюдаемых при развитии заболевания. В настоящее время показано, что существенное влияние на патогенез БП могут оказывать изменения на уровне транскриптома. В работе были использованы мышиные модели досимптомной стадии БП, поздней досимптомной и ранней симптомной (РСС) стадиями БП. Для полнотранскриптомного анализа пулов РНК тканей черной субстанции и стриатума мозга мышей использовались микрочипы MouseRef-8 v2.0 Expression BeadChip Kit («Illumina», США). Полученные данные указывают на последовательное вовлечение транскриптома в патогенез БП, а также на то, что изменения на транскриптомном уровне процессов транспорта и митохондриального биогенеза могут играть важную роль в нейродегенерации при БП уже на самых ранних этапах. Parkinson’s disease (PD) is a complex systemic disease, mainly associated with the death of dopaminergic neurons. Despite the obvious progress made in the study of molecular genetic factors and mechanisms of PD pathogenesis, it has now become clear that violations in the DNA structure do not describe the entire spectrum of pathological changes observed during the development of the disease. It has now been shown that changes at the transcriptome level can have a significant effect on the pathogenesis of PD. The authors used models of the presymptomatic stage of PD with mice decapitation after 6 hours (6 h-PSS), presymptomatic stage with decapitation after 24 hours (24 h-PSS), advanced presymptomatic (Adv-PSS) and early symptomatic (ESS) stages of PD. For whole transcriptome analysis of RNA pools of the substantia nigra and mouse striatum, the MouseRef-8 v2.0 Expression BeadChip Kit microchips (Illumina, USA) were used. As a result of the analysis of whole transcriptome data, it was shown that, there are a greater number of statistically significant changes in the tissues of the brain and peripheral blood of mice with Adv-PSS and ESS models of PD compared to 6 h-PSS and 24 h-PSS models. In general, the obtained data indicate the sequential involvement of the transcriptome in the pathogenesis of PD, as well as the fact that changes at the transcriptome level of the processes of transport and mitochondrial biogenesis can play an important role in neurodegeneration in PD at an early stage.

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Faculty Opinions recommendation of Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736045520.793568974 ◽

2019 ◽

Author(s):

Y Peng Loh ◽

Ashley Xiao

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Brain Models ◽

The Brain

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Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

Current Pharmaceutical Design ◽

10.2174/1381612826666200128145124 ◽

2020 ◽

Vol 26 (37) ◽

pp. 4721-4737 ◽

Cited By ~ 4

Author(s):

Bhumika Kumar ◽

Mukesh Pandey ◽

Faheem H. Pottoo ◽

Faizana Fayaz ◽

Anjali Sharma ◽

...

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Parkinson's Disease ◽

Side Effects ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Brain Targeting ◽

Neural Cells ◽

Blood Brain ◽

The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

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Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

Current Pharmaceutical Design ◽

10.2174/1381612825666191113103537 ◽

2020 ◽

Vol 25 (42) ◽

pp. 4510-4522 ◽

Cited By ~ 5

Author(s):

Biancamaria Longoni ◽

Irene Fasciani ◽

Shivakumar Kolachalam ◽

Ilaria Pietrantoni ◽

Francesco Marampon ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Potential Role ◽

Current Knowledge ◽

Biological Fluids ◽

Cell Communication ◽

Target Cells ◽

Cellular Debris ◽

The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

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Comparison of Cytocidal Activities of L-DOPA and Dopamine in S. cerevisiae and C. glabrata

Current Bioactive Compounds ◽

10.2174/1573407214666180108144216 ◽

2020 ◽

Vol 16 (1) ◽

pp. 90-93

Author(s):

Carmen E. Iriarte ◽

Ian G. Macreadie

Keyword(s):

Saccharomyces Cerevisiae ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Candida Glabrata ◽

High Sensitivity ◽

Time Dependent ◽

Colony Forming Units ◽

Dependent Cell ◽

The Brain

Background: Parkinson's Disease results from a loss of dopaminergic neurons, and reduced levels of the neurotransmitter dopamine. Parkinson's Disease treatments involve increasing dopamine levels through administration of L-DOPA, which can cross the blood brain barrier and be converted to dopamine in the brain. The toxicity of dopamine has previously studied but there has been little study of L-DOPA toxicity. Methods: We have compared the toxicity of dopamine and L-DOPA in the yeasts, Saccharomyces cerevisiae and Candida glabrata by cell viability assays, measuring colony forming units. Results: L-DOPA and dopamine caused time-dependent cell killing in Candida glabrata while only dopamine caused such effects in Saccharomyces cerevisiae. The toxicity of L-DOPA is much lower than dopamine. Conclusion: Candida glabrata exhibits high sensitivity to L-DOPA and may have advantages for studying the cytotoxicity of L-DOPA.

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Neuroinflammation and protein pathology in Parkinson’s disease dementia

Acta Neuropathologica Communications ◽

10.1186/s40478-020-01083-5 ◽

2020 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Antonina Kouli ◽

Marta Camacho ◽

Kieren Allinson ◽

Caroline H. Williams-Gray

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

T Lymphocytes ◽

Substantia Nigra ◽

Amyloid Β ◽

Brain Regions ◽

Parkinson’S Disease Dementia ◽

Activated Microglia ◽

Cell Counts ◽

The Brain

AbstractParkinson’s disease dementia is neuropathologically characterized by aggregates of α-synuclein (Lewy bodies) in limbic and neocortical areas of the brain with additional involvement of Alzheimer’s disease-type pathology. Whilst immune activation is well-described in Parkinson’s disease (PD), how it links to protein aggregation and its role in PD dementia has not been explored. We hypothesized that neuroinflammatory processes are a critical contributor to the pathology of PDD. To address this hypothesis, we examined 7 brain regions at postmortem from 17 PD patients with no dementia (PDND), 11 patients with PD dementia (PDD), and 14 age and sex-matched neurologically healthy controls. Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases. In contrast, there was no difference in either tau or amyloid-β pathology between the groups in any of the examined regions. Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region. Significant infiltration of CD4+ T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala. Amongst PDND/PDD cases, CD4+ T cell counts in the amygdala correlated with activated microglia, α-synuclein and tau pathology. Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala. The evidence presented in this study show an increased immune response in limbic and cortical brain regions, including increased microglial activation, infiltration of T lymphocytes, upregulation of pro-inflammatory cytokines and TLR gene expression, which has not been previously reported in the postmortem PDD brain.

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Neuronal loss in the colon of constipated Parkinson's disease patients mimics that in the brain

Biomedicine & Pharmacotherapy ◽

10.1016/0753-3322(96)87666-9 ◽

1996 ◽

Vol 50 (5) ◽

pp. 231-232

Author(s):

C Singaram

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neuronal Loss ◽

The Brain

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Evading the Immune System: Immune Modulation and Immune Matching in Cell Replacement Therapies for Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-212608 ◽

2021 ◽

pp. 1-6

Author(s):

Asuka Morizane ◽

Jun Takahashi

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Stem Cell ◽

Pluripotent Stem Cells ◽

Immune Modulation ◽

Autologous Transplantation ◽

Human Leukocyte ◽

Allogeneic Transplantation ◽

Leukocyte Antigen ◽

The Brain

Stem cell-based therapies for Parkinson’s disease are now being applied clinically. Notably, studies have shown that controlling the graft-induced immune response improves the results. In this mini-review, we concisely summarize current approaches used for this control. We focus on four modes of stem cell-based therapies: autologous transplantation, allogeneic transplantation with human leukocyte antigen-matching and allogeneic transplantation without, and finally the application of “universal” pluripotent stem cells. We also discuss immuno-suppressive treatments and the monitoring of immune reactions in the brain.

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