Studies of lipopolysaccharide effects on the induction of α-synuclein pathology by exogenous fibrils in transgenic mice

Molecular Neurodegeneration

Benoit I. Giasson¹  Todd E. Golde¹  Jasie K. Howard¹  Thomas B. Ladd¹  Carolina Ceballos-Diaz¹  Mieu Brooks¹  Amanda N. Sacino¹  Nicola J. Rutherford¹ 

[1] Center for Translational Research in Neurodegenerative Disease, Department of Neuroscience, University of Florida, 1275 Center Drive, Room BMS J-483, Gainesville 32610, FL, USA

关键词: Parkinson’s disease;    Neuroinflammation;    Transgenic mice;    α-synuclein pathology;    Lipopolysaccharide;   

Others  :  1221411
DOI  :  10.1186/s13024-015-0029-4

 received in 2015-05-26, accepted in 2015-07-22,  发布年份 2015

【 摘 要 】

Background

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is pathologically characterized by loss of dopaminergic neurons from the substantia nigra, the presence of aggregated α-synuclein (αS) and evidence of neuroinflammation. Experimental studies have shown that the cerebral injection of recombinant fibrillar αS, especially in αS transgenic mouse models, can induce the formation and spread of αS inclusion pathology. However, studies reporting this phenomenon did not consider the presence of lipopolysaccharide (LPS) in the injected αS, produced in E. coli, as a potential confound. The objectives of this study are to develop a method to remove the LPS contamination and investigate the differences in pathologies induced by αS containing LPS or αS highly purified of LPS.

Results and conclusions

We were able to remove >99.5 % of the LPS contamination from the αS preparations through the addition of a cation exchange step during purification. The αS pathology induced by injection of fibrils produced from αS containing LPS or purified of LPS, showed a similar distribution pattern; however, there was less spread into the cortex of the mice injected with αS containing higher levels of LPS. As previously reported, injection of αS fibrils could induce astrogliosis, and αS inclusions were present within astrocytes in mice injected with fibrils comprised of αS with or without cation exchange purification. Furthermore, we identified the presence of αS pathology in ependymal cells in both groups of mice, which suggests the involvement of a novel mechanism for spread in this model of αS pathology.

【 授权许可】

   
2015 Rutherford et al.

【 图 表 】

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