α-突触核蛋白
转基因小鼠
小胶质细胞
突触核蛋白
淀粉样蛋白(真菌学)
共核细胞病
转基因
化学
神经退行性变
黑质
医学
神经炎症
体内
病理
细胞生物学
作者
Renee C Gentzel,Dawn Toolan,Sarah Jinn,Joel B. Schachter,Lei Ma,Philipp J. Kahle,Sean C. Smith,Jacob Marcus
标识
DOI:10.1016/j.neurobiolaging.2021.05.012
摘要
Synucleinopathies are neurodegenerative disorders involving pathological alpha-synuclein (αSyn) protein, including dementia with Lewy bodies, multiple system atrophy and Parkinson's disease (PD). Current in vivo models of synucleinopathy include transgenic mice overexpressing αSyn variants and methods based on administration of aggregated, exogenous αSyn. Combining these techniques offers the ability to study consequences of introducing pathological αSyn into primed neuronal environments likely to develop synucleinopathy. Herein, we characterize the impacts pre-formed fibrils (PFFs) of recombinant, human αSyn have in mice overexpressing human A30P αSyn, a mutation associated with autosomal dominant PD. A30P mouse brain contains detergent insoluble αSyn biochemically similar to PD brain, and these mice develop Lewy-like synucleinopathy with age. Administration of PFFs in A30P mice resulted in regionally-specific accumulations of phosphorylated synuclein, microglial induction and a motor phenotype that differed from PFF-induced effects in wildtype mice. Surprisingly, PFF-induced losses of tyrosine hydroxylase were similar in A30P and wildtype mice. Thus, the PFF-A30P model recapitulates key aspects of synucleinopathy with induction of microglia, creating an appropriate system for evaluating neurodegenerative therapeutics.
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