Clinica Neurologica, Università di Perugia, Ospedale S. Maria della Misericordia, S. Andrea delle Fratte, 06156 Perugia, Italy.
Brain. 2012 Jun;135(Pt 6):1884-99. doi: 10.1093/brain/aws101. Epub 2012 May 4.
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.
尽管帕金森病患者在疾病早期就表现出认知功能障碍，但这种病理学中认知障碍的突触机制尚不清楚。海马长时程增强代表了学习和记忆相关突触变化的主要实验模型，并且受内源性多巴胺的控制。我们发现，神经毒性和转基因帕金森病模型中均存在海马长时程增强的改变，这种可塑性改变与多巴胺能传递受损和突触 N-甲基-D-天冬氨酸受体 NR2A/NR2B 亚基比值降低有关。在偏侧帕金森病和突变动物中也发现了海马依赖性学习的缺陷。有趣的是，多巴胺前体 l-多巴通过 D1/D5 受体能够恢复海马突触增强，并改善帕金森病动物的认知缺陷，表明海马长时程增强的多巴胺能依赖性损伤可能导致帕金森病患者的认知缺陷。
