Microglial Activation and Inflammation as a Factor in the Pathogenesis of Progressive Supranuclear Palsy (PSP)

Alster, Piotr; Madetko, Natalia; Koziorowski, Dariusz; Friedman, Andrzej

doi:10.3389/fnins.2020.00893

Cited by 35 publications

(32 citation statements)

References 63 publications

(76 reference statements)

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“…Previous studies have reported that FtMt expression is induced by ROS and inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, in the human neuroblastoma cell line IMR-32 [22,26]. Moreover, ROS and inflammatory cytokines are involved in the pathophysiology of PSP [2].…”

Section: Expression and Localization Of Ftmt In Pspmentioning

confidence: 96%

Immunohistochemical Study of Mitochondrial Ferritin in the Midbrain of Patients with Progressive Supranuclear Palsy

Bakar

Kato

Yanagisawa

et al. 2021

Acta Histochem. Cytochem

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Mitochondrial ferritin (FtMt) is a novel ferritin that is localized in the mitochondria. FtMt expression is low in the liver and spleen, and high in the heart, testis, and brain. We previously detected FtMt in dopaminergic neurons in the substantia nigra pars compacta (SNc) in human and monkey midbrains. We investigated the localization and expression of FtMt in the midbrain of patients with progressive supranuclear palsy (PSP) and controls using a monoclonal antibody (C65-2) against human FtMt. FtMt immunoreactivity was weakly detected in neuromelanin-containing neurons in the SNc and ventral tegmental area (VTA) of control cases compared with PSP, which exhibited a remarkable increase in FtMt immunoreactivity. Preincubation of C65-2 with the immunizing FtMt peptide significantly reduced the staining, indicating the specificity of C65-2. Several puncta were observed outside the neurons of PSP, in contrast with the control cases. Double immunofluorescence histochemistry for FtMt and tyrosine hydroxylase (TH), glial fibrillary acidic protein, and Iba1 showed localization of FtMt in dopaminergic neurons, microglia, and astrocytes in PSP. Furthermore, FtMt immunoreactivity was detected in a few TH-negative neurons. In the SNc and VTA, FtMt immunoreactivity colocalized with phosphorylated tau immunoreactivity. Our results indicate that FtMt is involved in the pathology of PSP. Clarifying the involvement of FtMt in PSP is of great interest.

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Section: Expression and Localization Of Ftmt In Pspmentioning

confidence: 96%

Immunohistochemical Study of Mitochondrial Ferritin in the Midbrain of Patients with Progressive Supranuclear Palsy

Bakar

Kato

Yanagisawa

et al. 2021

Acta Histochem. Cytochem

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“…An immunological component may therefore be discussed in early disease stages. The neuroinflammatory hypothesis of PSP suggests microglia activation even in early stages of the disease and expression of proinflammatory cytokines, linking neuroinflammation with neurodegeneration, thus contributing to the pathogenesis of PSP ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Ocular Motor Abnormalities in Anti-IgLON5 Disease

et al. 2021

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ObjectiveAnti-IgLON5 disease forms an interface between neuroinflammation and neurodegeneration and includes clinical phenotypes that are often similar to those of neurodegenerative diseases. An early diagnosis of patients with anti-IgLON5 disease and differentiation from neurodegenerative diseases is necessary and may have therapeutic implications.MethodsIn our small sample size study we investigated oculomotor function as a differentiating factor between anti-IgLON5 disease and neurodegenerative disorders. We examined ocular motor and vestibular function in four patients suffering from anti-IgLON5 disease using video-oculography (VOG) and a computer-controlled rotational chair system (sampling rate 60 Hz) and compared the data with those from ten age-matched patients suffering from progressive supranuclear palsy (PSP) and healthy controls (CON).ResultsPatients suffering from anti-IgLON5 disease differed from PSP most strikingly in terms of saccade velocity and accuracy, the presence of square wave jerks (SWJ) (anti-IgLON5 0/4 vs. PSP 9/10) and the clinical finding of supranuclear gaze palsy (anti-IgLON5 1/4). The presence of nystagmus, analysis of smooth pursuit eye movements, VOR and VOR suppression was reliable to differentiate between the two disease entities. Clear differences in all parameters, although not always significant, were found between all patients and CON.DiscussionWe conclude that the use of VOG as a tool for clinical neurophysiological assessment can be helpful in differentiating between patients with PSP and patients with anti-IgLON5 disease. VOG could have particular value in patients with suspected PSP and lack of typical Parkinson’s characteristics. future trials are indispensable to assess the potential of oculomotor function as a biomarker in anti-IgLON5 disease.

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“…In the future, both indirect (e.g., changes in hospital care utilization) and direct health effects (e.g., possible causation or exacerbation of NDD) of the COVID-19 pandemic most likely will continue to affect people living with NDD. Even if some studies suggest a causal role of SARS-CoV-2 for neurodegeneration [ 19 ], long-term data on COVID-19-related incidence of NDD and conclusive evidence on underlying mechanisms, such as neurodegeneration secondary to microglial neuroinflammation [ 20 ], are currently lacking [ 21 , 22 , 23 ]. Therefore, the question whether or not the COVID-19 pandemic may lead to increased numbers of NDD admissions in the long-term can only be answered by future epidemiological research [ 21 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Hospital Admissions for Neurodegenerative Diseases during the First Wave of the COVID-19 Pandemic: A Nationwide Cross-Sectional Study from Germany

et al. 2021

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(1) Background: The COVID-19 pandemic impacts healthcare utilization across all care settings and health conditions. The objective of this study was to determine changes in hospital admissions for neurodegenerative diseases (NDD) during the first COVID-19 wave in Germany; (2) Methods: This cross-sectional study used nationwide administrative claims data covering 1468 hospitals. The primary outcome was the year-to-year relative change in case numbers during a four-month study period (16 January–15 May 2020 vs. 2019) during the first pandemic wave. Secondary outcomes included year-to-year relative changes during a four-week peak phase (16 March–15 April) and changes between differential phases of the wave. The analyzed NDD comprised progressive supranuclear palsy (PSP), multiple system atrophy (MSA), Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and Huntington’s disease; (3) Results: Hospital admissions for any reason decreased by 16.7% in 2020 during the study period and by 36.6% during the peak phase, whereas admissions for NDD decreased by 27.6% and 65.0%, respectively. PSP cases decreased during the study period (−34.7%) and the peak phase (−68.1%) and stayed reduced in a late phase with falling COVID-19 numbers. MSA and ALS cases increased strongest after the peak, with ALS cases being comparatively weakly reduced during the study period (−17.3%) and peak phase (−51.7%); (4) Conclusions: Inpatient care utilization for NDD changed differentially during the first wave of the COVID-19 pandemic in Germany and showed a greater reduction than overall and general neurological admissions. Mitigating long-term health deterioration of this vulnerable subgroup is important to reduce morbidity and mortality in the future.

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Microglial Activation and Inflammation as a Factor in the Pathogenesis of Progressive Supranuclear Palsy (PSP)

Cited by 35 publications

References 63 publications

Immunohistochemical Study of Mitochondrial Ferritin in the Midbrain of Patients with Progressive Supranuclear Palsy

Immunohistochemical Study of Mitochondrial Ferritin in the Midbrain of Patients with Progressive Supranuclear Palsy

Ocular Motor Abnormalities in Anti-IgLON5 Disease

Hospital Admissions for Neurodegenerative Diseases during the First Wave of the COVID-19 Pandemic: A Nationwide Cross-Sectional Study from Germany

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