scholarly journals Serotonergic dysfunction in the A53T alpha-synuclein mouse model of Parkinson's disease

2015 ◽  
Vol 135 (3) ◽  
pp. 589-597 ◽  
Author(s):  
Janina Deusser ◽  
Stefanie Schmidt ◽  
Benjamin Ettle ◽  
Sonja Plötz ◽  
Sabine Huber ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Alpha Synuclein ◽  
Serotonergic Dysfunction

Gut bacterial composition in a mouse model of Parkinson’s disease

2018 ◽  
Vol 9 (5) ◽  
pp. 799-814 ◽  
Author(s):  
P. Perez-Pardo ◽  
H.B. Dodiya ◽  
P.A. Engen ◽  
A. Naqib ◽  
C.B. Forsyth ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Intestinal Inflammation ◽  
Alpha Synuclein ◽  
Enteric Neurons ◽  
Intestinal Epithelial ◽  
Bacterial Composition ◽  
Alpha Synuclein Aggregation ◽  
First Time

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.

scholarly journals Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson's disease

2013 ◽  
Vol 29 (8) ◽  
pp. 999-1009 ◽  
Author(s):  
Leo P. Kelly ◽  
Paul M. Carvey ◽  
Ali Keshavarzian ◽  
Kathleen M. Shannon ◽  
Maliha Shaikh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Intestinal Permeability ◽  
Alpha Synuclein ◽  
Permeability Changes

scholarly journals ATH434 Reverses Colorectal Dysfunction in the A53T Mouse Model of Parkinson’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Shanti Diwakarla ◽  
Rachel M. McQuade ◽  
Remy Constable ◽  
Olivia Artaiz ◽  
Enie Lei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Iron Chelator ◽  
Alpha Synuclein ◽  
Enteric Neurons ◽  
Potential Clinical Benefit ◽  
Enteric Neuropathy ◽  
Orally Bioavailable

Background: Gastrointestinal (GI) complications, that severely impact patient quality of life, are a common occurrence in patients with Parkinson’s disease (PD). Damage to enteric neurons and the accumulation of alpha-synuclein in the enteric nervous system (ENS) are thought to contribute to this phenotype. Copper or iron chelators, that bind excess or labile metal ions, can prevent aggregation of alpha-synuclein in the brain and alleviate motor-symptoms in preclinical models of PD. Objective: We investigated the effect of ATH434 (formally PBT434), a small molecule, orally bioavailable, moderate-affinity iron chelator, on colonic propulsion and whole gut transit in A53T alpha-synuclein transgenic mice. Methods: Mice were fed ATH434 (30 mg/kg/day) for either 4 months (beginning at ∼15 months of age), after the onset of slowed propulsion (“treatment group”), or for 3 months (beginning at ∼12 months of age), prior to slowed propulsion (“prevention group”). Results: ATH434, given after dysfunction was established, resulted in a reversal of slowed colonic propulsion and gut transit deficits in A53T mice to WT levels. In addition, ATH434 administered from 12 months prevented the slowed bead expulsion at 15 months but did not alter deficits in gut transit time when compared to vehicle-treated A53T mice. The proportion of neurons with nuclear Hu+ translocation, an indicator of neuronal stress in the ENS, was significantly greater in A53T than WT mice, and was reduced in both groups when ATH434 was administered. Conclusion: ATH434 can reverse some of the GI deficits and enteric neuropathy that occur in a mouse model of PD, and thus may have potential clinical benefit in alleviating the GI dysfunctions associated with PD.

scholarly journals Autophagy Inhibition and Inflammation Activation Induced by Phosphorylated Alpha-synuclein Through Toll-like Receptor 2 Pathway in the Hippocampus of MPTP Mouse Model of Parkinson’s Disease Contribute to Its Cognitive Function Decline in the Early Stage

2020 ◽  
Author(s):  
Ke-Zhong Zhang ◽  
Jing Wu ◽  
Wenwen Jiang ◽  
Ye Wang ◽  
Zhe Rong ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Function ◽  
Mouse Model ◽  
Early Stage ◽  
Alpha Synuclein ◽  
The Novel ◽  
Maze Test ◽  
Y Maze ◽  
Autophagy Inhibition

Abstract Background: To evaluate consecutively the cognitive function of a chronic mouse model of Parkinson’s disease (PD) induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p) in different modeling periods, and to study the characteristics of cognitive decline in PD and its molecular mechanism.Methods: In this study, we used MPTP and probenecid to induce a chronic PD mouse model, the Y-maze test to evaluate the cognitive function of the model in different modeling periods, western blotting (WB) to quantify phosphorylated alpha-synuclein (p-α-syn), Toll-like receptors (TLRs), Nod-like receptors (NLRs), Choline acetyltransferase (ChAT), glial fibrillary acidic protein (GFAP), p62, Interleukin-1β (IL-1β) and other related indicators, immunohistochemical staining (IHC) to characterize the expression of p-α-syn, immunofluorescence staining (IF) to observe the co-localization of p-α-syn and cholinergic neurons (ChAT+) or astroglias (GFAP+) in the hippocampus. The TLR2 inhibitor CU-CPT22 was used to intervene in the subacute MPTP PD mouse model and then the expression of TLR2, ChAT, GFAP, p62 and IL-1β were evaluated again. Results: In the Y-maze test after 1/2/3/4/5 weeks of administration, the percentage of bouts to the Novel arm and the percentage of duration in the Novel arm of the MPTP/p group mice were lower than those of the Saline group mice, and there were statistical differences at the second week. At the same time, the p-α-syn monomer in the hippocampus of chronic MPTP/p PD mice increased, accompanied by the increase of GFAP, TLR2, Nuclear factor-κB (NF-κB), NLR pyrin domain containing 3 (NLRP3), p62 and IL-1β, and the decrease of the ratio of LC3Ⅱ to LC3I (LC3Ⅱ/I). The p-α-syn in the hippocampus increased, and co-localized significantly with GFAP and slightly with ChAT. TLR2 inhibitor CU-CPT22 can reduce the expression of GFAP, p62 and IL-1β in the subacute MPTP mouse model.Conclusion: Autophagy inhibition and inflammation activation induced by p-α-syn through TLR2 pathway in the hippocampus of MPTP mouse model of Parkinson’s disease contribute to its cognitive function decline in the early stage, indicating the potential of TLR2 as a therapeutic target for PD cognitive decline.

Conditional control of human wildtype and mutated [A30P] alpha-synuclein in a mouse model of Parkinson's disease

2005 ◽  
Vol 32 (S 4) ◽  
Author(s):  
S Nuber ◽  
T Schmidt ◽  
H.W Habbes ◽  
M Löbbecke-Schumacher ◽  
P Teismann ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Alpha Synuclein ◽  
Conditional Control
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