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- Title
Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson’s disease.
- Authors
Costa, Cinzia; Sgobio, Carmelo; Siliquini, Sabrina; Tozzi, Alessandro; Tantucci, Michela; Ghiglieri, Veronica; Di Filippo, Massimiliano; Pendolino, Valentina; de Iure, Antonio; Marti, Matteo; Morari, Michele; Spillantini, Maria Grazia; Latagliata, Emanuele Claudio; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Gardoni, Fabrizio; Di Luca, Monica; Picconi, Barbara; Calabresi, Paolo
- Abstract
Although patients with Parkinson’s disease show impairments in cognitive performance even at the early stage of the disease, the synaptic mechanisms underlying cognitive impairment in this pathology are unknown. Hippocampal long-term potentiation represents the major experimental model for the synaptic changes underlying learning and memory and is controlled by endogenous dopamine. We found that hippocampal long-term potentiation is altered in both a neurotoxic and transgenic model of Parkinson’s disease and this plastic alteration is associated with an impaired dopaminergic transmission and a decrease of NR2A/NR2B subunit ratio in synaptic N-methyl-d-aspartic acid receptors. Deficits in hippocampal-dependent learning were also found in hemiparkinsonian and mutant animals. Interestingly, the dopamine precursor l-DOPA was able to restore hippocampal synaptic potentiation via D1/D5 receptors and to ameliorate the cognitive deficit in parkinsonian animals suggesting that dopamine-dependent impairment of hippocampal long-term potentiation may contribute to cognitive deficits in patients with Parkinson’s disease.
- Subjects
HIPPOCAMPUS diseases; PARKINSON'S disease; LONG-term potentiation; DOPAMINE regulation; NEUROTOXICOLOGY; DOPAMINERGIC mechanisms; COGNITION disorders; ASPARTIC acid metabolism
- Publication
Brain: A Journal of Neurology, 2012, Vol 135, Issue 6, p1884
- ISSN
0006-8950
- Publication type
Article
- DOI
10.1093/brain/aws101