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3D Electron Microscopy Study of Synaptic Organization of the Normal Human Transentorhinal Cortex and Its Possible Alterations in Alzheimer's Disease

Domínguez-Álvaro, M ; Montero-Crespo, M ; Blazquez-Llorca, L ; DeFelipe, J ; Alonso-Nanclares, L

eNeuro, 2019-07, Vol.6 (4), p.ENEURO.0140-19.2019 [Periódico revisado por pares]

United States: Society for Neuroscience

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  • Título:
    3D Electron Microscopy Study of Synaptic Organization of the Normal Human Transentorhinal Cortex and Its Possible Alterations in Alzheimer's Disease
  • Autor: Domínguez-Álvaro, M ; Montero-Crespo, M ; Blazquez-Llorca, L ; DeFelipe, J ; Alonso-Nanclares, L
  • Assuntos: Adult ; Aged, 80 and over ; Alzheimer Disease - pathology ; Dendritic Spines - ultrastructure ; Entorhinal Cortex - ultrastructure ; Female ; Humans ; Imaging, Three-Dimensional ; Male ; Microscopy, Electron ; Middle Aged ; New Research ; Synapses - ultrastructure
  • É parte de: eNeuro, 2019-07, Vol.6 (4), p.ENEURO.0140-19.2019
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Author contributions: M.D.-A., M.M.-C., L.B.-L., and L.A.-N. performed research; M.D.-A. analyzed data; M.D.-A. and L.A.-N. wrote the paper; J.D. and L.A.-N. designed research.
    This work was funded by grants from the “Ministerio de Ciencia, Innovación y Universidades” (grant PGC2018-094307-B-I00), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain, CB06/05/0066), the Alzheimer’s Association (ZEN-15-321663), and the European Union’s Horizon 2020 Research and Innovation Program under grant agreement No. 785907 (Human Brain Project, second specific grant agreement [SGA2]). M.M.-C. was awarded an FPU contract (14/02245) from the Spanish “Ministerio de Educación, Cultura y Deporte” (MECD).
    The authors declare no competing financial interests.
  • Descrição: 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 hypotheses is that synaptopathy (synaptic alterations and loss) represents the major structural correlate of the cognitive decline observed in AD. However, very few electron microscope (EM) 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 EM (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 synapses (AS) and symmetric synapses (SS) 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.
  • Editor: United States: Society for Neuroscience
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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