Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease

Cinzia Costa, Carmelo Sgobio, Sabrina Siliquini, Alessandro Tozzi, Michela Tantucci, Veronica Ghiglieri, Massimiliano Di Filippo, Valentina Pendolino, Antonio De Iure, Matteo Marti, Michele Morari, Maria Grazia Spillantini, Emanuele Claudio Latagliata, Tiziana Pascucci, Stefano Puglisi-Allegra, Fabrizio Gardoni, Monica Di Luca, Barbara Picconi, Paolo Calabresi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1884-1899
Number of pages16
JournalBrain
Volume135
Issue number6
DOIs
Publication statusPublished - 2012

Keywords

  • CA1 area
  • dementia
  • dopamine
  • glutamate
  • synaptic plasticity
  • α-synuclein

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    Costa, C., Sgobio, C., Siliquini, S., Tozzi, A., Tantucci, M., Ghiglieri, V., Di Filippo, M., Pendolino, V., De Iure, A., Marti, M., Morari, M., Spillantini, M. G., Latagliata, E. C., Pascucci, T., Puglisi-Allegra, S., Gardoni, F., Di Luca, M., Picconi, B., & Calabresi, P. (2012). Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease. Brain, 135(6), 1884-1899. https://doi.org/10.1093/brain/aws101