Premium
P1‐106: A MULTIPLEX MASS SPECTROMETRY METHOD FOR CHARACTERIZATION AND QUANTIFICATION OF α‐ AND β‐SYNUCLEINS IN BRAIN TISSUE: APPLICATION TO TRANSGENIC MOUSE MODELS OF PARKINSON'S DISEASE
Author(s) -
Singh Serena,
Khayachi Anouar,
Milnerwood Austen J.,
DeMarco Mari L.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.661
Subject(s) - multiplex , synuclein , chemistry , genetically modified mouse , parkinson's disease , synucleinopathies , pathology , biology , transgene , biochemistry , alpha synuclein , medicine , disease , bioinformatics , gene
examination and Western blot analysis of gliosis by measuring GFAP and IBA1 expression in hippocampus. The effects of aSyn0 were analyzed in wild type and Prnp0/0 mice. The mice were pre-treated with anti-inflammatory drugs and Tool-like receptor 2 (TLR2) antagonist, the long lasting effect of inflammation by LPS injection (2.5 mg/kg, ip) on the cognitive decline induced by aSyn0 was also examined. Results: The ICV application of a-Syn0 induced a cognitive decline determined by NORT, the memory impairment was associated with glial activation in hippocampus. The pre-treatment with ibuprofen or indomethacin not only extinguished the gliosis but also completely antagonized the behavioral deficit induced by a-Syn0, similar effect was obtained with TL-R2 antagonist. Conversely, the ICV injection of a-Syn0 at an ineffective concentration in mice controls became toxic when applied to mice pre-treated with a single dose of LPS, one month before. The absence of PrPc did not affect the detrimental effects, in vitro neurotoxicity memory deficit and hippocampal gliosis, induced by a-Syn0. Accordingly surface plasmon resonance analyses ruled out PrPc–a-Syn0 binding. Conclusions: Our findings indicate the important role played by inflammation in neuronal dysfunction induced by a-Syn0 presumably through TLR2 activation, chronic inflammatory state exacerbate a-Syn0 toxicity while PrPc neither binds a-Syn0 nor mediates their detrimental actions. these evidence might orientate future therapeutic approaches to synucleinopathies.