Ruiter Marvin, Lützkendorf Christine, Liang Jian, Wierenga Corette J
Department of Cell Biology, Neurobiology and Biophysics, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
J Alzheimers Dis Rep. 2021 Feb 27;5(1):153-160. doi: 10.3233/ADR-200291.
The amyloid-β protein precursor is highly expressed in a subset of inhibitory neuron in the hippocampus, and inhibitory neurons have been suggested to play an important role in early Alzheimer's disease plaque load. Here we investigated bouton dynamics in axons of hippocampal interneurons in two independent amyloidosis models. Short-term (24 h) amyloid-β (Aβ)-oligomer application to organotypic hippocampal slices slightly increased inhibitory bouton dynamics, but bouton density and dynamics were unchanged in hippocampus slices of young-adult -mice, in which Aβ levels are chronically elevated. These results indicate that loss or defective adaptation of inhibitory synapses are not a major contribution to Aβ-induced hyperexcitability.
淀粉样β蛋白前体在海马体中一部分抑制性神经元中高度表达,并且有研究表明抑制性神经元在早期阿尔茨海默病斑块负荷中起重要作用。在此,我们在两个独立的淀粉样变性模型中研究了海马中间神经元轴突中的突触小体动态变化。对器官型海马切片短期(24小时)应用淀粉样β(Aβ)寡聚体可轻微增加抑制性突触小体动态变化,但在成年前期β-淀粉样前体蛋白裂解酶1基因敲除(APP/PS1)小鼠的海马切片中,突触小体密度和动态变化未改变,在这些小鼠中Aβ水平长期升高。这些结果表明,抑制性突触的丧失或适应性缺陷并非Aβ诱导的兴奋性过高的主要原因。