scholarly journals Neuroinflammation in Parkinson's Disease and Related Disorders: A Lesson from Genetically Manipulated Mouse Models ofα-Synucleinopathies

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Kazunari Sekiyama ◽  
Shuei Sugama ◽  
Masayo Fujita ◽  
Akio Sekigawa ◽  
Yoshiki Takamatsu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Mouse Models ◽  
Glial Cells ◽  
Genetic Modification ◽  
Early Stage ◽  
Related Model ◽  
Genetically Manipulated

Neuroinflammation in Parkinson's disease (PD) is a chronic process that is associated with alteration of glial cells, including astrocytes and microglia. However, the precise mechanisms remain obscure. To better understand neuroinflammation in PD, we focused on glial activation inα-synuclein (αS) transgenic and related model mice. In the majority ofαS transgenic mice, astrogliosis was observed concomitantly with accumulation ofαS during the early stage of neurodegeneration. However, microglia were not extensively activated unless the mice were treated with lipopolysaccharides or through further genetic modification of other molecules, including familial PD risk factors. Thus, the results inαS transgenic mice and related model mice are consistent with the idea that neuroinflammation in PD is a double-edged sword that is protective in the early stage of neurodegeneration but becomes detrimental with disease progression.

scholarly journals Deep Brain Stimulation Complications in Patients With Parkinson’s Disease and Surgical Modifications: A Single-Center Retrospective Analysis

2021 ◽  
Vol 15 ◽  
Author(s):  
Shuo Xu ◽  
Wenfei Wang ◽  
Si Chen ◽  
Qianqian Wu ◽  
Chao Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Early Stage ◽  
Univariate Analysis ◽  
Unplanned Readmission ◽  
Consecutive Series ◽  
Deep Brain

BackgroundAs a complication-prone operation, deep brain stimulation (DBS) has become the first-line surgical approach for patients with advanced Parkinson’s disease (PD). This study aimed to evaluate the incidence and risk factors of DBS-associated complications.MethodsWe have reviewed a consecutive series of patients with PD undergoing DBS procedures to describe the type, severity, management, and outcome of postoperative complications from January 2011 to December 2018. Both univariate and multivariate analyses were performed to identify statistically significant risk factors. We also described our surgical strategies to minimize the adverse events.ResultsA total of 225 patients underwent 229 DBS implantation procedures (440 electrodes), of whom 20 patients experienced 23 DBS-associated complications, including ten operation-related complications and 13 hardware-related ones. Univariate analysis elucidated that comorbid medical conditions (P = 0.024), hypertension (P = 0.003), early-stage operation (P < 0.001), and unilateral electrode implantation (P = 0.029) as risk factors for overall complications, or more specifically, operation-related complications demonstrated in the stratified analysis. In contrast, no risk factor for hardware-related complications was identified. Statistical significances of hypertension (OR = 3.33, 95% CI: 1.14–9.71, P = 0.027) and early-stage (OR = 11.04, 95% CI: 2.42–50.45, P = 0.002) were further validated via multivariate analysis. As the annual number of DBS procedures increased, the incidence of complications gradually decreased (R = −0.699, P < 0.01). Additionally, there was a strong correlation between surgical complications and unplanned readmission (R = 0.730, P < 0.01).ConclusionThe importance of cumulative experience and relevant technique modifications should be addressed to prevent DBS-associated complications and unplanned readmission.

scholarly journals Spinal Cord Pathology in Alpha-Synuclein Transgenic Mice

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sonja Mendritzki ◽  
Saskia Schmidt ◽  
Teresa Sczepan ◽  
Xin-Ran Zhu ◽  
Daniel Segelcke ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Spinal Cord ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Transgenic Mice ◽  
Glial Cells ◽  
Alpha Synuclein ◽  
Motor Impairments ◽  
Neuron Death ◽  
Severe Motor

Accumulation ofα-synuclein is observed in neurodegenerative diseases like Parkinson's disease and Multiple System Atrophy. In previous studies with transgenic C57BL/6 mice overexpressingα-synuclein carrying the mutations A53T and A30P found in Parkinson's disease or with a parkin-null background, we reported severe mitochondrial impairments in neurons and to a larger extent in glial cells of the mesencephalon. Neuron death was not observed in the brain. Here we show that the mice show severe motor impairments in behavioral tests. In addition, these mice exhibit astrocytic cell death in the spinal cord, accompanied by extensive gliosis and microglial activation. This is shown by cell death staining and immunohistochemistry. Ultrastructural analyses revealed severe mitochondrial impairments not only in astrocytes, but also in oligodendrocytes and, to a small extent, in neurons. Thus, the transgenic mice show a profound pathology in glial cells of the spinal cord.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

Gene expression analysis in modeling Parkinson’s disease

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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