Resilience of striatal synaptic plasticity over early structural adaptations in premotor parkinsonism

• Published in: NPJ Parkinson's Disease Vol. 11; no. 1; pp. 146 - 13
• Main Authors: Merino-Galán, Leyre, Zamarbide, Marta, Belloso-Iguerategui, Arantzazu, Alonso-Moreno, Marta C., Gago, Belén, Reinares-Sebastián, Alejandro, Blesa, Javier, Dumitriu, Dani, Quiroga-Varela, Ana, Rodríguez-Oroz, María Cruz
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.06.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378; 631/378/1689; 631/378/1689/1718; Biomedical and Life Sciences; Biomedicine; Cell death; Dopamine; Morphology; Neurology; Neurosciences; Parkinson's disease; Synapses
• ISSN: 2373-8057; 2373-8057
• DOI: 10.1038/s41531-025-00994-1

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.