Anesthesiology Institute, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, 9500 Euclid Ave. - NB3-78, Cleveland, Ohio 44195.
Hippocampus. 2018 Aug;28(8):549-556. doi: 10.1002/hipo.22955. Epub 2018 May 7.
Silent glutamatergic synapses lacking functional AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate) receptors exist in several brain regions including the hippocampus. Their involvement in the dysfunction of hippocampal glutamatergic transmission in the setting of Alzheimer's disease (AD) is unknown. This study demonstrated a decrease in the percentage of silent synapses in rats microinjected with amyloid fibrils (Aβ ) into the hippocampal CA1. Also, pairing low-frequency electric stimuli failed to induce activation of the hippocampal silent synapses in the modeled rats. Immunoblotting studies revealed a decreased expression of GluR1 subunits in the hippocampal CA1 synaptosomal preparation, indicating a potential reduction in the GluR1 subunits anchoring in postsynaptic density in the modeled rats. We also noted a decreased expression of phosphorylated cofilin, which regulates the function of actin cytoskeleton and receptor trafficking, and reduced expression of the scaffolding protein PSD95 in the hippocampal CA1 synaptosome in rats injected with Aβ . Taken together, this study illustrates dysfunction of hippocampal silent synapse in the rodent model of AD, which might result from the impairments of actin cytoskeleton and postsynaptic scaffolding proteins induced by amyloid fibrils.
在包括海马体在内的几个脑区存在缺乏功能性 AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体的沉默谷氨酸能突触。其在阿尔茨海默病（AD）中海马谷氨酸能传递功能障碍中的作用尚不清楚。本研究表明，在向海马 CA1 内注射淀粉样纤维（Aβ）的大鼠中，沉默突触的百分比减少。此外，低频电刺激未能诱导模型大鼠海马沉默突触的激活。免疫印迹研究显示，海马体 CA1 突触小体制备物中 GluR1 亚基的表达减少，表明模型大鼠中突触后密度中 GluR1 亚基的锚定可能减少。我们还注意到，磷酸化丝切蛋白的表达减少，它调节肌动蛋白细胞骨架和受体转运的功能，以及在注射 Aβ 的大鼠海马 CA1 突触小体中 PSD95 支架蛋白的表达减少。总之，这项研究说明了 AD 啮齿动物模型中海马体沉默突触的功能障碍，这可能是由淀粉样纤维诱导的肌动蛋白细胞骨架和突触后支架蛋白的损伤引起的。
