Yuan Xiang PingAn, Janc Oliwia, Grochowska Katarzyna M, Kreutz Michael R, Reymann Klaus G
Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany.
RG Neuropharmacology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Neurobiol Aging. 2016 Apr;40:98-102. doi: 10.1016/j.neurobiolaging.2016.01.008. Epub 2016 Jan 21.
Soluble forms of oligomeric amyloid beta (AβO) are involved in the loss of synaptic plasticity and memory, especially in early phases of Alzheimer's disease. Stimulation of dopamine D1/D5 receptors (D1R/D5R) is known to increase surface expression of synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate subtype glutamate and N-methyl-D-aspartate subtype glutamate receptors and facilitates the induction of the late phase of long-term potentiation (LTP), probably via a related mechanism. In this study, we show that the D1/D5R agonist SKF38393 protects LTP of hippocampal CA1 synapses from the deleterious action of oligomeric amyloid beta. Unexpectedly, the D1R/D5R-mediated recovery of LTP is independent of protein kinase A or phospholipase C pathways. Instead, we found that the inhibition of Src-family tyrosine kinases completely abolished the protective effects of D1R/D5R stimulation in a cellular model of learning and memory.
可溶性寡聚淀粉样β蛋白（AβO）与突触可塑性和记忆丧失有关，尤其是在阿尔茨海默病的早期阶段。已知刺激多巴胺D1/D5受体（D1R/D5R）可增加突触α-氨基-3-羟基-5-甲基-4-异恶唑丙酸亚型谷氨酸受体和N-甲基-D-天冬氨酸亚型谷氨酸受体的表面表达，并可能通过相关机制促进晚期长时程增强（LTP）的诱导。在本研究中，我们表明D1/D5R激动剂SKF38393可保护海马CA1突触的LTP免受寡聚淀粉样β蛋白的有害作用。出乎意料的是，D1R/D5R介导的LTP恢复独立于蛋白激酶A或磷脂酶C途径。相反，我们发现在学习和记忆的细胞模型中，抑制Src家族酪氨酸激酶完全消除了D1R/D5R刺激的保护作用。
