Speaker
Description
Parkinson’s Disease (PD) is a neurodegenerative pathology characterized by loss of dopaminergic neurons (DANs) of the substantia nigra, accumulation and aggregation of 𝜶-synuclein (αSYN), and neuroinflammation. Neuroinflammation is a risk factor to PD development, moreover the pathology is characterized by a correlation between levels of proinflammatory cytokines and disease severity, a consistent activation of microglia and recruitment of CD4+ and CD8+ T cells from the perifery since early stages of the disease. Studying the role of neuroinflammation in PD requires establishing its reproducibility across various mouse models, a fundamental step in the research process. Therefore, our group conducted an extensive comparative analysis of the levels of neurodegeneration, microglial activation and T lymphocytes infiltration levels in the substantia nigra pars compacta (SNpc) of different mouse models. These parameters were assessed by tyrosine hydroxylase (TH) staining for DANs counting, immunodecoration for microglial Iba1 activation marker and CD3, CD4 and CD8 to detect lymphocytic infiltrations. Specifically, we studied mice exhibiting pathology through αSYN-induced neurodegeneration. The overexpression of αSYN was obtained by local SNpc administration of αSYN preformed fibrils (PFFs) or delivery of the human wild-type SNCA gene by either lentiviral or adeno-associated viral vectors. Additionally, we utilized Cre-inducible models with DAN or microglial specificity for the expression of αSYN limited to specific cell types. We demonstrated a tight correlation between αSYN accumulation, neurodegeneration and neuroinflammation in most of the models. We also showed that accumulation of αSYN in glial cells rather than in DANs alone determined higher levels of neuroinflammation and neurodegeneration, highlighting the role of these cells in the pathogenic process. Furthermore, microglial activation and T lymphocytes infiltration precedes the loss of DANs in our LV-SNCA mouse model, showing how the immune response and neuroinflammation are key aspects to determine neurodegeneration and the development of the pathology.
| Author(s) | Alice Calderoni* (1), Simone Bido (1), Melania Nannoni (1, 2, 3), Sharon Muggeo (1), Diana Gambarè (1), Giorgia Ruffini (1), Mirko Luoni (1, 2), Martino Provinciali (1), Serena Giannelli (1), Vania Broccoli (1,2) |
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| Affiliation(s) | "(1) San Raffaele Scientific Institute, Milan, Italy (2) National Research Council (CNR), Institute of Neuroscience, Milan, Italy (3) Milano-Bicocca University, Milan, Italy" |
