Reference : Neurodegeneration and neuroinflammation are linked, but independent of a-synuclein in...
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
Human health sciences : Neurology
Systems Biomedicine
http://hdl.handle.net/10993/50437
Neurodegeneration and neuroinflammation are linked, but independent of a-synuclein inclusions, in a seeding/spreading mouse model of Parkinson's disease
English
Garcia, Pierre mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology]
Wemheuer, W. [> >]
Uriarte, O. [> >]
Michelucci, Alessandro [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) >]
Masuch, A. [> >]
Brioschi, S. [> >]
Weihofen, A. [> >]
Koncina, Eric mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)]
Coowar, Djalil mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services]
Heurtaux, Tony mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)]
Glaab, Enrico mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Biomedical Data Science]
Balling, Rudolf [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Sousa, C. [> >]
Kaoma, T. [> >]
Nicot, N. [> >]
Pfander, T. [> >]
Schulz-Schaeffer, W. [> >]
Allouche, A. [> >]
Fischer, N. [> >]
Biber, K. [> >]
Mittelbronn, Michel [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Ostaszewski, Marek mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core]
Schmit, Kristopher mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology >]
Buttini, Manuel mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuropathology]
2022
Glia
John Wiley & Sons
Yes (verified by ORBilu)
International
0894-1491
1098-1136
Hoboken
NY
[en] Parkinson's disease ; mouse models ; microglia ; inflammation ; spreading model ; alpha-synuclein ; neurodegeneration ; gene expression ; brain
[en] A key pathological process in Parkinson's disease (PD) is the transneuronal spreading of α-synuclein. Alpha-synuclein (α-syn) is a presynaptic protein that, in PD, forms pathological inclusions. Other hallmarks of PD include neurodegeneration and microgliosis in susceptible brain regions. Whether it is primarily transneuronal spreading of α-syn particles, inclusion formation, or other mechanisms, such as inflammation, that cause neurodegeneration in PD is unclear. We used a model of spreading of α-syn induced by striatal injection of α-syn preformed fibrils into the mouse striatum to address this question. We performed quantitative analysis for α-syn inclusions, neurodegeneration, and microgliosis in different brain regions, and generated gene expression profiles of the ventral midbrain, at two different timepoints after disease induction. We observed significant neurodegeneration and microgliosis in brain regions not only with, but also without α-syn inclusions. We also observed prominent microgliosis in injured brain regions that did not correlate with neurodegeneration nor with inclusion load. Using longitudinal gene expression profiling, we observed early gene expression changes, linked to neuroinflammation, that preceded neurodegeneration, indicating an active role of microglia in this process. Altered gene pathways overlapped with those typical of PD. Our observations indicate that α-syn inclusion formation is not the major driver in the early phases of PD-like neurodegeneration, but that microglia, activated by diffusible, oligomeric α-syn, may play a key role in this process. Our findings uncover new features of α-syn induced pathologies, in particular microgliosis, and point to the necessity for a broader view of the process of α-syn spreading.
Luxembourg Centre for Systems Biomedicine (LCSB)
Fonds National de la Recherche - FnR
FNR AFR 5712281, FNR AFR 12515776, FNR PEARL P16/BM/11192868
Researchers ; Professionals ; Students
http://hdl.handle.net/10993/50437
10.1002/glia.24149
http://doi.org/10.1002/glia.24149
The original publication is available at http://doi.org/10.1002/glia.24149
FnR ; FNR11192868 > Michel Mittelbronn > NPath > Chair In Neuropathology > 01/01/2017 > 30/06/2022 > 2016

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