Unbound MEDLINE

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

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.

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  • Publisher Full Text

    • Authors

    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 MG, Latagliata EC, Pascucci T, Puglisi-Allegra S, Gardoni F, Di Luca M, Picconi B, Calabresi P

    Institution

    Clinica Neurologica, Università di Perugia, Ospedale S. Maria della Misericordia, S. Andrea delle Fratte, 06156 Perugia, Italy.

    Source

    Brain : a journal of neurology 135:Pt 6 2012 Jun pg 1884-99

    MeSH

    Analysis of Variance
    Animals
    Antiparkinson Agents
    Benserazide
    Biophysical Phenomena
    Disease Models, Animal
    Dopamine
    Electric Stimulation
    Excitatory Postsynaptic Potentials
    Exploratory Behavior
    Hippocampus
    Humans
    Levodopa
    Long-Term Potentiation
    Male
    Memory Disorders
    Mice
    Mice, Inbred C57BL
    Mice, Transgenic
    Microdialysis
    Mutation
    Oxidopamine
    Parkinson Disease
    Patch-Clamp Techniques
    Rats
    Subcellular Fractions
    Sympatholytics
    Synaptosomes
    Tritium
    Tyrosine 3-Monooxygenase
    alpha-Synuclein

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22561640