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Characterizing αSyn Pre‐Formed Fibril Animal Models and Exploring Endpoints Beyond αSyn for Parkinson Disease
Author(s) -
Gocal Wiktoria,
Gentzel Renee,
Marcus Jacob
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.802.52
Subject(s) - neurodegeneration , parkinson's disease , neuropathology , microglia , alpha synuclein , pathology , immune system , fibril , immunohistochemistry , synucleinopathies , biology , synuclein , inflammation , chemistry , microbiology and biotechnology , medicine , immunology , disease , biochemistry
The second most common neurodegenerative disease, Parkinson disease (PD), has been characterized by conformational mutations in the synaptic protein, alpha‐synuclein (αSyn). In the disease state, the protein becomes increasingly insoluble and aggregates, forming Lewy bodies and impairing cellular function, as seen in PD. To further study this synucleinopathy in animals, a model has been established in which αSyn Lewy bodies are induced through the addition of exogenous αSyn preformed fibrils (PFFs) (Luk et al., 2009). These PFFs allow for the “seeding” of endogenous αSyn, producing the Lewy body neuropathology typical of PD. Our group used this seeding model in‐vivo , by injecting 4 uL and 8 uL doses of 2 ug/ul PFFs directly into the striatum of wild‐type rats, and histologically examining the spread of the pathology 30 days later. Pathological αSyn is correlated with phosphorylation of the protein at serine129 (pSer129), and thus all samples were stained for pSer129 using immunohistochemistry methods at the 30 day time point. Additional endpoints were also explored to better understand the biology of PD. Aside from αSyn accumulation, PD is also characterized by neurodegeneration that could be due to an inflammatory or immune response to the aggregated protein. To explore this relationship, immunohistochemistry staining was performed for glial marker Iba‐1 to visualize microglia and GFAP to visualize astrocytes. Staining was also performed for lymphocyte‐activation gene 3 (LAG3) and major histocompatibility complex II (MHCII) as markers for a potential immune response. These results will enrich understanding of additional inflammation and immune components of this rodent model of PD. Support or Funding Information Merck Research Laboratories This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .