Department of Pharmacology, Wuxi Higher Health Vocational Technology School, Wuxi, Jiangsu Province, People's Republic of China.
Brain Res. 2013 Jun 17;1515:88-97. doi: 10.1016/j.brainres.2013.03.049. Epub 2013 Apr 9.
Beta-amyloid peptide (Aβ) has a causal role in the pathophysiology of Alzheimer's disease (AD). Recent studies indicate that Aβ can disrupt excitatory glutamatergic synaptic function at synaptic level. However, the underlying mechanisms remain obscure. In this study, we recorded evoked and spontaneous EPSCs in hippocampal CA1 pyramidal neurons via whole-cell voltage-clamping methods and found that 1 μM Aβ can induce acute depression of basal glutamatergic synaptic transmission through both presynaptic and postsynaptic dysfunction. Moreover, we also found that Aβ-induced both presynaptic and postsynaptic dysfunction can be reversed by the inhibitor of protein phosphatase 2B (PP2B), FK506, whereas only postsynaptic disruption can be ameliorated by the inhibitor of PP1/PP2A, Okadaic acid (OA). These results indicate that PP1/PP2A and PP2B have overlapping but not identical functions in Aβ-induced acute depression of excitatory glutamatergic synaptic transmission of hippocampal CA1 pyramidal neurons.
β-淀粉样肽（Aβ）在阿尔茨海默病（AD）的病理生理学中起因果作用。最近的研究表明，Aβ 可以在突触水平破坏兴奋性谷氨酸能突触功能。然而，其潜在的机制尚不清楚。在这项研究中，我们通过全细胞膜片钳电压钳方法记录了海马 CA1 锥体神经元的诱发和自发性 EPSC，并发现 1 μM Aβ 通过突触前和突触后功能障碍可诱导基础谷氨酸能突触传递的急性抑制。此外，我们还发现，Aβ 诱导的突触前和突触后功能障碍均可被蛋白磷酸酶 2B（PP2B）抑制剂 FK506 逆转，而仅突触后破坏可被蛋白磷酸酶 1/2A（PP1/PP2A）抑制剂 OKADAIC 酸（OA）改善。这些结果表明，在 Aβ 诱导的海马 CA1 锥体神经元兴奋性谷氨酸能突触传递的急性抑制中，PP1/PP2A 和 PP2B 具有重叠但不相同的功能。
