演題詳細
Poster
パーキンソン病とその類縁疾患
Parkinson's Disease and Related Disorders
開催日 | 2014/9/12 |
---|---|
時間 | 14:00 - 15:00 |
会場 | Poster / Exhibition(Event Hall B) |
αシヌクレインオリゴマーはスパイク後過分極の増強により大脳皮質錐体細胞における発火頻度を抑制する
α-synuclein oligomers suppress spike frequency by enhancing afterhyperpolarization in neocortical pyramidal neurons
- P2-296
- 山本 兼司 / Kenji Yamamoto:1 澤田 秀幸 / Hideyuki Sawada:1
- 1:国立病院機構宇多野病院、臨床研究部・神経内科 / Clinical Research Center & Dept of Neurology, Utano National hospital
α-synuclein, which is a major component of Lewy bodies, has been linked to the pathogenesis of Parkinson's disease and dementia with Lewy bodies. Despite increasing evidence suggests that soluble oligomers rather than insoluble mature fibrils, are the pathogenic species, how the soluble α-synuclein oligomers accumulate intracellularly and alter neuronal activities into pathological condition, has not been studied directly. We examined the action of α-synuclein on neuronal excitabilities by injecting α-synuclein protein into pyramidal neurons in mouse frontal cortical slices through whole-cell patch pipettes. Western blot analysis showed that the pipette solution including α-synuclein incubated with dopamine for 3 days (α-SN+DA), had higher order oligomer in comparison with α-synuclein-containing solution without dopamine (α-SN). Intracellular application of α-SN+DA significantly suppressed spike firing during current injection compared with α-SN, but did not altered resting membrane potential, spike width, spike after depolarization, and H current. Nimodipine and apamin blocked the effect of α-SN+DA on spike firing. α-SN+DA prolonged the duration of spike afterhyperpolarization (AHP) and increased the charge transfer carried by the current elicited by depolarization pulses that would produce AHP under current clamp (IAHP), both of which were inhibited by apamin. These results suggest that α-synuclein oligomers reduce spike frequency by enhancing AHP, which may cause the downregulation of neocortical activities in Parkinson's disease and dementia with Lewy bodies.