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

• Published in: Brain (London, England : 1878) Vol. 135; no. Pt 6; pp. 1884 - 1899
• Main Authors: COSTA, Cinzia, SGOBIO, Carmelo, MORARI, Michele, GRAZIA SPILLANTINI, Maria, CLAUDIO LATAGLIATA, Emanuele, PASCUCCI, Tiziana, PUGLISI-ALLEGRA, Stefano, GARDONI, Fabrizio, DI LUCA, Monica, PICCONI, Barbara, CALABRESI, Paolo, SILIQUINI, Sabrina, TOZZI, Alessandro, TANTUCCI, Michela, GHIGLIERI, Veronica, DI FILIPPO, Massimiliano, PENDOLINO, Valentina, DE LURE, Antonio, MARTI, Matteo
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.2012
• Subjects: alpha-Synuclein - genetics; Analysis of Variance; Animals; Antiparkinson Agents - pharmacology; Antiparkinson Agents - therapeutic use; Benserazide - pharmacology; Benserazide - therapeutic use; Biological and medical sciences; Biophysical Phenomena - drug effects; Biophysical Phenomena - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Dopamine - metabolism; Electric Stimulation; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - genetics; Excitatory Postsynaptic Potentials - physiology; Exploratory Behavior - drug effects; Hippocampus - physiopathology; Humans; Levodopa - pharmacology; Levodopa - therapeutic use; Long-Term Potentiation - drug effects; Long-Term Potentiation - genetics; Long-Term Potentiation - physiology; Male; Medical sciences; Memory Disorders - drug therapy; Memory Disorders - etiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microdialysis - methods; Mutation - genetics; Neurology; Oxidopamine - toxicity; Parkinson Disease - complications; Parkinson Disease - drug therapy; Parkinson Disease - etiology; Parkinson Disease - pathology; Patch-Clamp Techniques; Radionuclide Imaging; Rats; Subcellular Fractions - drug effects; Subcellular Fractions - metabolism; Sympatholytics - toxicity; Synaptosomes - diagnostic imaging; Synaptosomes - drug effects; Tritium - metabolism; Tyrosine 3-Monooxygenase - metabolism; Potentiation; Nervous system diseases; Dopamine; Memory; Central nervous system; Parkinson disease; CA1 area; Catecholamine; Glutamate; Encephalon; Cerebral disorder; Experimental disease; Central nervous system disease; Synaptic plasticity; Excitatory aminoacid; Neurotransmitter; Degenerative disease; Hippocampus; α-synuclein; Extrapyramidal syndrome; Dementia
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/aws101

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.