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.

Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease / C. Costa, C. Sgobio, S. Siliquini, A. Tozzi, M. Tantucci, V. Ghiglieri, M. Di Filippo, V. Pendolino, A. De Iure, M. Marti, M. Morari, M.G. Spillantini, E.C. Latagliata, T. Pascucci, S. Puglisi-Allegra, F. Gardoni, M.M.G. Di Luca, B. Picconi, P. Calabresi. - In: BRAIN. - ISSN 0006-8950. - 135:6(2012), pp. 1884-1899. [10.1093/brain/aws101]

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

F. Gardoni;M.M.G. Di Luca;
2012

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.
α-synuclein; CA1 area; dementia; dopamine; glutamate; synaptic plasticity
Settore BIO/14 - Farmacologia
   Restorative Plasticity At Corticostriatal Excitatory Synapses
   REPLACES
   EUROPEAN COMMISSION
   FP7
   222918
2012
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/211210
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