Resilience of striatal synaptic plasticity over early structural adaptations in premotor parkinsonism
Parkinson's disease has a long premotor phase with ongoing dopaminergic degeneration, yet its compensatory mechanisms remain unclear. Using a rat model with A53T α-synuclein overexpression in the substantia nigra, we analyzed striatal synaptic changes at 72 h, 1, 2, and 4 weeks post-inoculation, before motor signs appeared. Dopamine concentration decreased from 72 h, and chemical long-term potentiation was simultaneously inhibited, partially recovering by 4 weeks. At this time point, dopaminergic degeneration and post-synaptic morphological and ultrastructural dendritic spine remodelling became significant. These changes included a reduction in thin dendritic spines, an increase in mushroom spine head volume, a decrease in smooth endoplasmic reticulum-containing spines, and an increase in dendritic branching. In conclusion, impaired striatal dopaminergic neurotransmisson diminishes striatal synaptic plasticity, which can be partially restored through complex structural changes in striatal spines. These adaptations might represent fundamental homeostatic mechanisms regulating synaptic function during the premotor stage of Parkinson's disease.
Authors
- Ana Quiroga‐Varela (ORCID: https://orcid.org/0000-0003-1989-7113)
- Arantzazu Belloso-Iguerategui (ORCID: https://orcid.org/0000-0002-6327-6392)
- Alejandro Reinares-Sebastián (ORCID: https://orcid.org/0000-0003-1632-4432)
- Belén Gago (ORCID: https://orcid.org/0000-0002-7770-9806)
- María Rodríguez‐Oroz (ORCID: https://orcid.org/0000-0001-5962-772X)
- Marta Zamarbide (ORCID: https://orcid.org/0000-0002-4449-1345)
- Leyre Merino-Galán (ORCID: https://orcid.org/0000-0003-2623-9987)
- Javier Blesa (ORCID: https://orcid.org/0000-0002-4257-1325)
- Dani Dumitriu (ORCID: https://orcid.org/0000-0002-7873-5192)
- Marta C Alonso-Moreno (ORCID: https://orcid.org/0009-0004-9071-3801)
Institutions
- University of the Basque Country (ES)
- University of California, San Francisco (US)
- Columbia University Irving Medical Center (US)
- Instituto de Salud Carlos III (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Centro de Investigación Biomédica en Red (ES)
- HM Hospitales (ES)
- University Hospital HM Puerta del Sur (ES)
- Centro de Biología Molecular Severo Ochoa (ES)
- Instituto de Investigación Biomédica de Málaga (ES)
- Camilo José Cela University (ES)
- Universidad Autónoma de Madrid (ES)
- Universidad de Málaga (ES)
- Universidad de Navarra (ES)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-06-03
- DOI
- https://doi.org/10.1038/s41531-025-00994-1
- Citations
- 4
- Primary Topic
- Neurological disorders and treatments
- Type
- article
- Field-Weighted Citation Impact
- 5.56
Funders
- Michael J. Fox Foundation for Parkinson's Research
- Boehringer Ingelheim Fonds
- Euskal Herriko Unibertsitatea
- Instituto de Salud Carlos III
- European Regional Development Fund