Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous amyloid β peptide.
Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous amyloid β peptide.
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DOI：
10.1002/hipo.22403
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发表时间：
2015-07
期刊：
影响因子：
3.5
通讯作者：
Randall AD
中科院分区：
文献类型：
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作者：
Tamagnini F;Scullion S;Brown JT;Randall AD
β-淀粉样蛋白（Aβ）肽在人脑中的积累是阿尔茨海默病（AD）的典型病理学标志。最近在Aβ过表达转基因小鼠中的研究表明，脑Aβ水平升高可能与异常癫痫样活动相关。与此一致，这些小鼠也可以表现出皮质和海马神经元的内在兴奋性（IE）改变：这些观察结果可能与AD患者癫痫发作的患病率增加有关。在这项研究中，我们研究了用合成人Aβ 1-42肽的寡聚体制剂处理2-5 h后，海马CA 1锥体细胞中IE的变化。比较Aβ-（500 nM）和溶剂-（DMSO 0.05%）处理的小鼠海马切片的全细胞电流钳记录。可溶性Aβ处理未导致阈下固有特性（包括膜电位、输入电阻和超极化激活的“下垂”）发生改变。同样，在500 ms方波电流超阈值刺激诱发的放电曲线中未观察到变化。然而，Aβ 500 nM处理导致动作电位（AP）阈值超极化。此外，500 nM Aβ处理抑制了单个AP或50 Hz系列5 - 25个AP后的后超极化。这些数据表明，急性暴露于可溶性Aβ寡聚体对CA 1锥体神经元IE特性的影响与淀粉样蛋白病转基因模型中观察到的结果不同。然而，在慢性和急性模型中，IE的变化都是朝着兴奋过度的方向，这加强了淀粉样蛋白病和癫痫发作发生率增加可能与AD患者有因果关系的观点。© 2014 The Authors Hippocampus由Wiley Periodicals，Inc.
Accumulation of beta‐amyloid (Aβ) peptides in the human brain is a canonical pathological hallmark of Alzheimer's disease (AD). Recent work in Aβ‐overexpressing transgenic mice indicates that increased brain Aβ levels can be associated with aberrant epileptiform activity. In line with this, such mice can also exhibit altered intrinsic excitability (IE) of cortical and hippocampal neurons: these observations may relate to the increased prevalence of seizures in AD patients. In this study, we examined what changes in IE are produced in hippocampal CA1 pyramidal cells after 2–5 h treatment with an oligomeric preparation of synthetic human Aβ 1–42 peptide. Whole cell current clamp recordings were compared between Aβ‐(500 nM) and vehicle‐(DMSO 0.05%) treated hippocampal slices obtained from mice. The soluble Aβ treatment did not produce alterations in sub‐threshold intrinsic properties, including membrane potential, input resistance, and hyperpolarization activated “sag”. Similarly, no changes were noted in the firing profile evoked by 500 ms square current supra‐threshold stimuli. However, Aβ 500 nM treatment resulted in the hyperpolarization of the action potential (AP) threshold. In addition, treatment with Aβ at 500 nM depressed the after‐hyperpolarization that followed both a single AP or 50 Hz trains of a number of APs between 5 and 25. These data suggest that acute exposure to soluble Aβ oligomers affects IE properties of CA1 pyramidal neurons differently from outcomes seen in transgenic models of amyloidopathy. However, in both chronic and acute models, the IE changes are toward hyperexcitability, reinforcing the idea that amyloidopathy and increased incidence in seizures might be causally related in AD patients. © 2014 The Authors Hippocampus Published by Wiley Periodicals, Inc.