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Glial activation precedes alpha-synuclein pathology in a mouse model of Parkinson's disease

Izco, M; Blesa, J; Verona, G; Cooper, JM; Alvarez-Erviti, L; (2021) Glial activation precedes alpha-synuclein pathology in a mouse model of Parkinson's disease. Neuroscience Research , 170 pp. 330-340. 10.1016/j.neures.2020.11.004. Green open access

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Abstract

Neuroinflammation is increasingly recognized as an important feature in the pathogenesis of Parkinson's disease (PD). However, it remains unclear whether neuroinflammation contributes to nigral degeneration in PD or is merely a secondary marker of neurodegeneration. We aimed to investigate the temporal relationship between synucleopathy, neuroinflammation and nigrostriatal degeneration in a mouse model of PD. Mice received unilateral intrastriatal injection of alpha-synuclein pre-formed fibrils, alpha-synuclein monomer or vehicle and were sacrificed at 15, 30 and 90 days post-injection. Intrastriatal inoculation of alpha-synuclein fibrils led to significant alpha-synuclein aggregation in the substantia nigra peaking at 30 days after injection while the significant increase in Iba-1 cells, GFAP cells and IL-1β expression peaked earlier at 15 days. At 90 days, the striatal dopaminergic denervation was associated with astroglial activation. Alpha-synuclein monomer did not result in long-term glia activation or increase in inflammatory markers. The spread of alpha-synuclein aggregates into the cortex was not associated with any changes to neuroinflammatory markers. Our results demonstrate that in the substantia nigra glial activation is an early event that precedes alpha-synuclein inclusion formation, suggesting neuroinflammation could play an important early role in the pathogenesis of PD.

Type: Article
Title: Glial activation precedes alpha-synuclein pathology in a mouse model of Parkinson's disease
Location: Ireland
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neures.2020.11.004
Publisher version: https://doi.org/10.1016/j.neures.2020.11.004
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Alpha-Synuclein, Astrocytes, Microglia, Mouse model, Neuroinflammation, Parkinson’s disease
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10122500
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