title: 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.
authors.affiliation: Clinica Neurologica, Università di Perugia, Ospedale S. Maria della Misericordia, S. Andrea delle Fratte, 06156 Perugia, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Costa
authors.forename: Carmelo
authors.initials: C
authors.lastname: Sgobio
authors.forename: Sabrina
authors.initials: S
authors.lastname: Siliquini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tozzi
authors.forename: Michela
authors.initials: M
authors.lastname: Tantucci
authors.forename: Veronica
authors.initials: V
authors.lastname: Ghiglieri
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Di Filippo
authors.forename: Valentina
authors.initials: V
authors.lastname: Pendolino
authors.forename: Antonio
authors.initials: A
authors.lastname: de Iure
authors.forename: Matteo
authors.initials: M
authors.lastname: Marti
authors.forename: Michele
authors.initials: M
authors.lastname: Morari
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
authors.forename: Emanuele Claudio
authors.initials: EC
authors.lastname: Latagliata
authors.forename: Tiziana
authors.initials: T
authors.lastname: Pascucci
authors.forename: Stefano
authors.initials: S
authors.lastname: Puglisi-Allegra
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gardoni
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use; D001545:Benserazide / Q000494:pharmacology / Q000627:therapeutic use; D055592:Biophysical Phenomena / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017551:Microdialysis / Q000379:methods; D009154:Mutation / Q000235:genetics; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D018408:Patch-Clamp Techniques; D011877:Radionuclide Imaging; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013565:Sympatholytics / Q000633:toxicity; D013574:Synaptosomes / Q000000981:diagnostic imaging / Q000187:drug effects; D014316:Tritium / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics
chemical_list: D000978:Antiparkinson Agents; D013565:Sympatholytics; D051844:alpha-Synuclein; D014316:Tritium; D007980:Levodopa; D001545:Benserazide; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine