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Updated: Aug 17, 2026

Semi-Quantitative Determination of Dopaminergic Neuron Density in the Substantia Nigra of Rodent Models using Automated Image Analysis
Published on: February 2, 2021
Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition
Emilie Croisier1, Linda B Moran, David T Dexter
1Department of Neuropathology, Division of Neuroscience and Mental Health, Imperial College London, and Hammersmith Hospitals Trust, London, UK. e.croisier@imperial.ac.uk
Background:
The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease.
Methods:
We have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Using semi-quantitative severity ratings, we have examined the relationship between microglial activation, alpha-synuclein deposition, classical neuropathological criteria for PD, subtype of the disease and clinical course.
Results:
While we did not observe an association between microglial MHC class II expression and clinical parameters, we did find a correlation between disease duration and the macrophage marker CD68 which is expressed by phagocytic microglia. In addition, we observed a significant correlation between the degree of MHC class II expression and alpha-synuclein deposition in the substantia nigra in PD.
Conclusion:
While microglia appeared to respond to alpha-synuclein deposition, MHC class II antigen expression by microglia in the substantia nigra cannot be used as an indicator of clinical PD severity or disease progression. In addition, a contributory or even causative role for microglia in the neuronal loss associated with PD as suggested by some authors seems unlikely. Our data further suggest that an assessment of microglial activation in the aged brain on the basis of immunohistochemistry for MHC class II antigens alone should be done with caution.
Insights
Microglial activation markers like MHC class II do not reliably indicate Parkinson's disease severity. While microglia respond to alpha-synuclein, their direct role in Parkinson's pathogenesis appears unlikely.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- The precise roles of microglial activation and alpha-synuclein in Parkinson's disease (PD) pathogenesis are not fully understood.
- This study investigated whether microglial activation phenotypes correlate with PD's histopathological and clinical features.
Purpose of the Study:
- To test the hypothesis that microglia play a primary role in Parkinson's disease pathogenesis.
- To examine the relationship between microglial activation markers, alpha-synuclein deposition, and clinical/neuropathological features of PD.
Main Methods:
- Examined microglial MHC class II expression (activation marker) and CD68 (macrophage marker) in post-mortem substantia nigra from PD patients.
- Assessed alpha-synuclein immunoreactivity and correlated these with PD neuropathological criteria, disease subtype, and clinical course using semi-quantitative ratings.
Main Results:
- Microglial MHC class II expression did not correlate with clinical PD parameters.
- A correlation was found between disease duration and CD68 expression in phagocytic microglia.
- Significant correlation observed between MHC class II expression levels and alpha-synuclein deposition in the substantia nigra.
Conclusions:
- MHC class II expression in substantia nigra microglia is not a reliable indicator of clinical PD severity or progression.
- Microglia appear to react to alpha-synuclein, but a primary causative role in PD-associated neuronal loss seems improbable.
- Caution is advised when assessing microglial activation in aged brains using only MHC class II immunohistochemistry.
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