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

2021 ◽  
Vol 15 ◽  
Author(s):  
Thuy Thi Lai ◽  
Yun Joong Kim ◽  
Phuong Thi Nguyen ◽  
Young Ho Koh ◽  
Tinh Thi Nguyen ◽  
...  

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.

2021 ◽  
Author(s):  
Thuy Thi Lai ◽  
Yun Joong Kim ◽  
Phuong Thi Nguyen ◽  
Young Ho Koh ◽  
Tinh Thi Nguyen ◽  
...  

Abstract Alpha-synuclein (αSyn) propagation has been determined 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 yet to be well understood with regard to temporal relationship. In this study, by means of 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 responses including the microglia and astrocyte were activated at the earliest stage and reduced with time, and the phosphorylated form of αSyn accumulation increased behind it. Thereafter, the degeneration of striatal dopaminergic neurons became significant with the conspicuity of behavior phenotype. Similar pattern of forefront eruption of inflammation and following αSyn propagation was noted in the opposite striatum, which was not injected with PFF. Meanwhile, in analyzing the whole brain, inflammatory responses were determined to have activated at the earliest stage, and the soluble αSyn expression then increased concurrently. 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 PD mouse model. From this model, recognizing the temporal relationship between inflammation, αSyn propagation, and neurodegeneration may be helpful in establishing PD animal model and monitoring the effect of interventional therapy.


Neuroscience ◽  
2019 ◽  
Vol 414 ◽  
pp. 8-27 ◽  
Author(s):  
Madeline J. Churchill ◽  
Mark A. Cantu ◽  
Ella A. Kasanga ◽  
Cindy Moore ◽  
Michael F. Salvatore ◽  
...  

2015 ◽  
Vol 135 (3) ◽  
pp. 589-597 ◽  
Author(s):  
Janina Deusser ◽  
Stefanie Schmidt ◽  
Benjamin Ettle ◽  
Sonja Plötz ◽  
Sabine Huber ◽  
...  

2018 ◽  
Vol 9 (5) ◽  
pp. 799-814 ◽  
Author(s):  
P. Perez-Pardo ◽  
H.B. Dodiya ◽  
P.A. Engen ◽  
A. Naqib ◽  
C.B. Forsyth ◽  
...  

The mechanism of neurodegeneration in Parkinson’s disease (PD) remains unknown but it has been hypothesised that the intestinal tract could be an initiating and contributing factor to the neurodegenerative processes. In PD patients as well as in animal models for PD, alpha-synuclein-positive enteric neurons in the colon and evidence of colonic inflammation have been demonstrated. Moreover, several studies reported pro-inflammatory bacterial dysbiosis in PD patients. Here, we report for the first time significant changes in the composition of caecum mucosal associated and luminal microbiota and the associated metabolic pathways in a rotenone-induced mouse model for PD. The mouse model for PD, induced by the pesticide rotenone, is associated with an imbalance in the gut microbiota, characterised by a significant decrease in the relative abundance of the beneficial commensal bacteria genus Bifidobacterium. Overall, intestinal bacterial dysbiosis might play an important role in both the disruption of intestinal epithelial integrity and intestinal inflammation, which could lead or contribute to the observed alpha-synuclein aggregation and PD pathology in the intestine and central nervous system in the oral rotenone mouse model of PD.


2018 ◽  
Vol 9 ◽  
Author(s):  
Alice J. White ◽  
Ruwani S. Wijeyekoon ◽  
Kirsten M. Scott ◽  
Nushan P. Gunawardana ◽  
Shaista Hayat ◽  
...  

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