Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson’s disease overexpressing human alpha synuclein
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 symptoms on a genetic PD rat model that overexpresses human α-synuclein (Snca<sup>+/+</sup>) at a presymptomatic age, exposed to a pro-inflammatory insult by intraperitoneal injection of lipopolysaccharide (LPS), using immunohistology, high-dimensional flow cytometry, constant potential amperometry, and behavioral analyses. A single injection of LPS into WT and Snca<sup>+/+</sup> rats triggered long-lasting increase in the activation of pro-inflammatory microglial markers, monocytes, and T lymphocytes. However, only LPS Snca<sup>+/+</sup> rats showed dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), associated with a reduction in the release of evoked dopamine 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.
Authors
- Mariangela Massaro Cenere (ORCID: https://orcid.org/0000-0001-7758-8082)
- Beatrice Zarrilli
- Alessandro Matteocci (ORCID: https://orcid.org/0009-0007-4556-1257)
- Nicola Berretta (ORCID: https://orcid.org/0000-0001-8097-6238)
- Laura Petrosini (ORCID: https://orcid.org/0000-0001-7464-5168)
- Valerio Chiurchiù (ORCID: https://orcid.org/0000-0002-0316-7311)
- Debora Cutuli (ORCID: https://orcid.org/0000-0003-4788-2461)
- Ada Ledonne (ORCID: https://orcid.org/0000-0001-6302-207X)
- Nicolas Casadei (ORCID: https://orcid.org/0000-0003-2209-0580)
- Francesca R. Fusco (ORCID: https://orcid.org/0000-0003-2226-523X)
- Emanuela Paldino (ORCID: https://orcid.org/0000-0002-8483-543X)
- Marta Tiberi (ORCID: https://orcid.org/0000-0002-5287-424X)
- Cecilia Giacomet (ORCID: https://orcid.org/0000-0001-7210-5619)
- Francesca Cossa (ORCID: https://orcid.org/0000-0002-8072-1910)
- Mauro Federici (ORCID: https://orcid.org/0000-0003-4563-1677)
- Nicola Biagio Mercuri (ORCID: https://orcid.org/0000-0001-6700-7491)
- Sebastian Luca D’Addario (ORCID: https://orcid.org/0000-0001-9467-9584)
Institutions
- University of Rome Tor Vergata (IT)
- Istituto di Farmacologia Traslazionale (IT)
- Fondazione Santa Lucia (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- National Research Council (IT)
- Research Network (United States) (US)
- University of Tübingen (DE)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2024-11-05
- DOI
- https://doi.org/10.1038/s41531-024-00824-w
- Citations
- 12
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 4.43
Funders
- Michael J. Fox Foundation for Parkinson's Research
- Ministero dell’Istruzione, dell’Università e della Ricerca