Systemic inflammation triggers long-lasting neuroinflammation and accelerates neurodegeneration in a rat model of Parkinson’s disease overexpressing human α-synuclein
ABSTRACT Increasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson’s disease (PD). In the present study, we assessed the development of PD-like symptoms on a genetic PD rat model overexpressing human α-synuclein (Snca+/+) at a presymptomatic age, exposed to a pro-inflammatory insult by intraperitoneal injection of lipopolysaccharide (LPS), using immunohistology, high-dimensional flow cytometry, electrophysiology, and behavioral analyses. A single injection of LPS to both WT andSnca+/+rats triggered long-lasting increased activation of pro-inflammatory microglial markers, infiltrating monocytes and T-lymphocytes. However, only LPSSnca+/+rats displayed dopaminergic neuronal loss in thesubstantia nigra pars compacta(SNpc), associated with a reduction of evoked dopamine release in the striatum. No significant changes were observed in the behavioral domain.We propose our double-hit animal as a reliable model to investigate the mechanisms whereby α-synuclein and inflammation interact to promote neurodegeneration in PD..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 28. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Massaro Cenere, Mariangela [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.01.30.577912 |
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| PPN (Katalog-ID): |
XBI042349583 |
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| 520 | |a ABSTRACT Increasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson’s disease (PD). In the present study, we assessed the development of PD-like symptoms on a genetic PD rat model overexpressing human α-synuclein (Snca+/+) at a presymptomatic age, exposed to a pro-inflammatory insult by intraperitoneal injection of lipopolysaccharide (LPS), using immunohistology, high-dimensional flow cytometry, electrophysiology, and behavioral analyses. A single injection of LPS to both WT andSnca+/+rats triggered long-lasting increased activation of pro-inflammatory microglial markers, infiltrating monocytes and T-lymphocytes. However, only LPSSnca+/+rats displayed dopaminergic neuronal loss in thesubstantia nigra pars compacta(SNpc), associated with a reduction of evoked dopamine release in the striatum. No significant changes were observed in the behavioral domain.We propose our double-hit animal as a reliable model to investigate the mechanisms whereby α-synuclein and inflammation interact to promote neurodegeneration in PD. | ||
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| 700 | 1 | |a Paldino, Emanuela |0 (orcid)0000-0002-8483-543X |4 aut | |
| 700 | 1 | |a D’Addario, Sebastian Luca |0 (orcid)0000-0001-9467-9584 |4 aut | |
| 700 | 1 | |a Federici, Mauro |0 (orcid)0000-0003-4563-1677 |4 aut | |
| 700 | 1 | |a Giacomet, Cecilia |0 (orcid)0000-0001-7210-5619 |4 aut | |
| 700 | 1 | |a Cutuli, Debora |0 (orcid)0000-0003-4788-2461 |4 aut | |
| 700 | 1 | |a Matteocci, Alessandro |4 aut | |
| 700 | 1 | |a Cossa, Francesca |0 (orcid)0000-0002-8072-1910 |4 aut | |
| 700 | 1 | |a Zarrilli, Beatrice |0 (orcid)0000-0002-4704-5834 |4 aut | |
| 700 | 1 | |a Casadei, Nicolas |4 aut | |
| 700 | 1 | |a Ledonne, Ada |0 (orcid)0000-0001-6302-207X |4 aut | |
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| 700 | 1 | |a Chiurchiù, Valerio |0 (orcid)0000-0002-0316-7311 |4 aut | |
| 700 | 1 | |a Mercuri, Nicola B. |0 (orcid)0000-0001-6700-7491 |4 aut | |
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