Temporal Evolution of Inflammation and Neurodegeneration With Alpha-Synuclein Propagation in Parkinson's Disease Mouse Model

Frontiers in Integrative Neuroscience

Yun Joong Kim³  Hyeo-il Ma⁴  Thuy Thi Lai⁴  Young Eun Kim⁴  Tinh Thi Nguyen⁵  Phuong Thi Nguyen⁵  Young Ho Koh⁵ 

[1] Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, South Korea;Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University, Anyang, South Korea;Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea;Hallym Neurological Institute, Hallym University, Anyang, South Korea;Ilsong Institute of Life Science, Hallym University, Anyang, South Korea;

关键词: alpha-synuclein;    microglia;    astrocytes;    neurodegeneration;    Parkinson's disease;   

DOI  :  10.3389/fnint.2021.715190

来源: DOAJ

【 摘 要 】

According to a few studies, α-synuclein (αSyn) propagation has been suggested to play a key role in the pathomechanism of Parkinson's disease (PD), but neurodegeneration and the involvement of inflammation in its pathologic progression are not well understood with regard to temporal relationship. In this study, with the help of the PD mouse model injected with intrastriatal αSyn preformed fibril (PFF), the temporal evolution of αSyn propagation, inflammation, and neurodegeneration was explored in the perspective of the striatum and the whole brain. In the PFF-injected striatum, inflammatory response cells, including microglia and astrocytes, were activated at the earliest stage and reduced with time, and the phosphorylated form of αSyn accumulation increased behind it. Afterward, the degeneration of striatal dopaminergic neurons became significant with the conspicuity of behavioral phenotype. Similar patterns of forefront eruption of inflammation and then followed by αSyn propagation were noted in the opposite striatum, which were not injured by PFF injection. In analyzing the whole brain, inflammatory responses were activated at the earliest stage, and the soluble αSyn expression increased concurrently. The inflammatory response decreased afterward, and the accumulation of the insoluble form of αSyn increased behind it. Our results suggested that the inflammatory response may precede the accumulation of the pathologic form of αSyn; thereafter, the neurodegeneration and motor dysfunction followed αSyn proliferation in the PD mouse model. From this model, recognizing the temporal relationship between inflammation, αSyn propagation, and neurodegeneration may be helpful in establishing the PD animal model and monitoring the effect of interventional therapy.

【 授权许可】

Unknown