Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Pathophysiology
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: We aimed to analyze the influence of two microglia-related pathways on the accumulation of α-synuclein aggregates and neurodegeneration after intracerebral injection of sonicated murine α-synuclein fibrils in mice.
Background: One of the key processes during the pathogenesis of Parkinson´s disease (PD) and dementia with Lewy bodies (DLB) is the accumulation of α-synuclein aggregates in the human brain. The „prion-like“ spreading induced by accelerated seeding through intracranially injected α-synuclein fibrils in rodents has become a popular model to mimic this process. We asked if, and if so how, neuroinflammation influences this α-synuclein dependent process. In this context, we have chosen to investigate the role of two microglia-related pathways in mice injected with α-synuclein fibrils: The CD40/CD40L pathway, which is involved in microglia activation, and the fractalkine-dependant pathway, fractalkine (CX3CL1) being a chemokine that down-regulates microglia activity by binding to the corresponding receptor CX3CR1.
Methods: We have injected murine α-synuclein fibrils unilaterally into the striatum of wild-type mice C57Bl6/J as well as mice deficient for either the fractalkine receptor (CX3CR1) or CD40L and have measured the pathohistological outcomes. We focused our analyses on the quantification of α-synuclein aggregates in several brain regions, examination of microglia morphology, interactions of microglia with α-synuclein aggregates, and loss of dopaminergic neurons in the Substantia nigra.
Results: We found that fibril-injected CD40L knockout mice, while showing slightly less microglial activation, did not differ from their wildtype controls in measures of α-synuclein accumulation and of neurodegeneration. Experiments with the CX3CR1 knockout mice are in progress.
Conclusions: Our preliminary results indicate that removal of the CD40/CD40L signalling pathway does not influence α-synuclein spreading and its associated neurodegeneration. Studies on how a disruption of fractalkine-dependant signalling influences α-synuclein spreading and neurodegeneration are in progress.
To cite this abstract in AMA style:
W.M. Wemheuer, P. Garcia, E. Konica, A. Masuch, S. Brioschi, K. Biber, A. Weihofen, H. Kollmus, K. Schughart, D. Coowar, R. Balling, M. Buttini. Modulation of microglia function in the prion-like spreading of α-synuclein in the murine brain [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/modulation-of-microglia-function-in-the-prion-like-spreading-of-synuclein-in-the-murine-brain/. Accessed May 18, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/modulation-of-microglia-function-in-the-prion-like-spreading-of-synuclein-in-the-murine-brain/