3D Electron Microscopy study of synaptic organization of the normal human transentorhinal cortex and its possible alterations in Alzheimer's disease
3D Electron Microscopy study of synaptic organization of the normal human transentorhinal cortex and its possible alterations in Alzheimer's disease
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DOI：
10.1523/eneuro.0140-19.2019
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发表时间：
2019-07-01
期刊：
影响因子：
3.4
通讯作者：
Alonso-Nanclares, L.
中科院分区：
文献类型：
--
作者：
Dominguez-Alvaro, M.;Montero-Crespo, M.;Alonso-Nanclares, L.
经内嗅皮层（transentorhinal cortex，TEC）是位于内侧颞叶的一个斜向皮层，与内嗅皮层一起是阿尔茨海默病（Alzheimer's disease，AD）的首发受累区域。最广泛接受的假设之一是突触病（突触改变和丧失）代表在AD中观察到的认知下降的主要结构相关性。然而，可用的电子显微镜研究很少;间接估计突触密度的最常用的方法是通过在光显微镜水平上使用突触标记物对免疫反应性斑点进行计数。为了研究突触形态和与AD相关的可能改变，使用聚焦离子束/扫描电子显微镜（FIB/SEM）进行详细的三维（3D）超微结构分析在来自非痴呆受试者和AD患者的人脑样品中的TEC的第II层的神经元中进行。使用每个突触的3D重建来评估靶向棘或树突轴的不对称和对称突触（分别为AS和SS）的比例和形状。对4722个突触的3D分析显示，在对照组和AD病例中，AS的首选靶点是棘头，SS的首选靶点是树突轴。然而，在AD患者中，我们观察到靶向脊柱头部的突触百分比减少。关于突触的形状，在对照病例和AD样本中，绝大多数突触具有斑点形状，其次是穿孔或马蹄形突触，碎片突触是最不常见的类型。此外，比较显示AD患者中碎片AS的数量增加。
The transentorhinal cortex (TEC) is an obliquely oriented cortex located in the medial temporal lobe and, together with the entorhinal cortex, is one of the first affected areas in Alzheimer's disease (AD). One of the most widely accepted hypothesis is that synaptopathy (synaptic alterations and loss) represents the major structural correlate of the cognitive decline observed in AD. However, very few electron microscope studies are available; the most common method to estimate synaptic density indirectly is by counting -at the light microscopic level- immunoreactive puncta using synaptic markers.To investigate synaptic morphology and possible alterations related to AD, a detailed three-dimensional (3D) ultrastructural analysis using focused ion beam/scanning electron microscopy (FIB/SEM) was performed in the neuropil of layer II of the TEC in human brain samples from non-demented subjects and AD patients. Evaluation of the proportion and shape of asymmetric and symmetric synapses (AS and SS, respectively) targeting spines or dendritic shafts was performed using 3D reconstructions of every synapse. The 3D analysis of 4722 synapses revealed that the preferable targets were spine heads for AS and dendritic shafts for SS, both in control and AD cases. However, in AD patients, we observed a reduction in the percentage of synapses targeting spine heads. Regarding the shape of synapses, in both control cases and AD samples, the vast majority of synapses had a macular shape, followed by perforated or horseshoe-shaped synapses, with fragmented synapses being the least frequent type. Moreover, comparisons showed an increased number of fragmented AS in AD patients.