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Whole-Brain Three-Dimensional Profiling Reveals Brain Region Specific Axon Vulnerability in 5xFAD Mouse Model

Axonopathy is a pathological feature observed in both Alzheimer’s disease (AD) patients and animal models. However, identifying the temporal and regional progression of axonopathy during AD development remains elusive. Using the fluorescence micro-optical sectioning tomography system, we acquired wh...

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Autores principales: Zhang, Jianping, Long, Ben, Li, Anan, Sun, Qingtao, Tian, Jiaojiao, Luo, Ting, Ding, Zhangheng, Gong, Hui, Li, Xiangning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726261/
https://www.ncbi.nlm.nih.gov/pubmed/33324177
http://dx.doi.org/10.3389/fnana.2020.608177
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author Zhang, Jianping
Long, Ben
Li, Anan
Sun, Qingtao
Tian, Jiaojiao
Luo, Ting
Ding, Zhangheng
Gong, Hui
Li, Xiangning
author_facet Zhang, Jianping
Long, Ben
Li, Anan
Sun, Qingtao
Tian, Jiaojiao
Luo, Ting
Ding, Zhangheng
Gong, Hui
Li, Xiangning
author_sort Zhang, Jianping
collection PubMed
description Axonopathy is a pathological feature observed in both Alzheimer’s disease (AD) patients and animal models. However, identifying the temporal and regional progression of axonopathy during AD development remains elusive. Using the fluorescence micro-optical sectioning tomography system, we acquired whole-brain datasets in the early stage of 5xFAD/Thy1-GFP-M mice. We reported that among GFP labeled axons, GFP-positive axonopathy first formed in the lateral septal nucleus, subiculum, and medial mammillary nucleus. The axonopathy further increased in most brain regions during aging. However, most of the axonopathic varicosities disappeared significantly in the medial mammillary nucleus after 8 weeks old. Continuous three-dimensional datasets showed that axonopathy in the medial mammillary nucleus was mainly located on axons from hippocampal GFP-positive neurons. Using the rabies viral tracer in combination with immunohistochemistry, we found that axons in the medial mammillary nucleus from the subiculum were susceptible to lesions that prior to the occurrence of behavioral disorders. In conclusion, we created an early-stage spatiotemporal map of axonopathy in 5xFAD/Thy1-GFP-M mice and identified specific neural circuits which are vulnerable to axon lesions in an AD mouse model. These findings underline the importance of early interventions for AD, and may contribute to the understanding of its progression and its early symptom treatment.
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spelling pubmed-77262612020-12-14 Whole-Brain Three-Dimensional Profiling Reveals Brain Region Specific Axon Vulnerability in 5xFAD Mouse Model Zhang, Jianping Long, Ben Li, Anan Sun, Qingtao Tian, Jiaojiao Luo, Ting Ding, Zhangheng Gong, Hui Li, Xiangning Front Neuroanat Neuroanatomy Axonopathy is a pathological feature observed in both Alzheimer’s disease (AD) patients and animal models. However, identifying the temporal and regional progression of axonopathy during AD development remains elusive. Using the fluorescence micro-optical sectioning tomography system, we acquired whole-brain datasets in the early stage of 5xFAD/Thy1-GFP-M mice. We reported that among GFP labeled axons, GFP-positive axonopathy first formed in the lateral septal nucleus, subiculum, and medial mammillary nucleus. The axonopathy further increased in most brain regions during aging. However, most of the axonopathic varicosities disappeared significantly in the medial mammillary nucleus after 8 weeks old. Continuous three-dimensional datasets showed that axonopathy in the medial mammillary nucleus was mainly located on axons from hippocampal GFP-positive neurons. Using the rabies viral tracer in combination with immunohistochemistry, we found that axons in the medial mammillary nucleus from the subiculum were susceptible to lesions that prior to the occurrence of behavioral disorders. In conclusion, we created an early-stage spatiotemporal map of axonopathy in 5xFAD/Thy1-GFP-M mice and identified specific neural circuits which are vulnerable to axon lesions in an AD mouse model. These findings underline the importance of early interventions for AD, and may contribute to the understanding of its progression and its early symptom treatment. Frontiers Media S.A. 2020-11-26 /pmc/articles/PMC7726261/ /pubmed/33324177 http://dx.doi.org/10.3389/fnana.2020.608177 Text en Copyright © 2020 Zhang, Long, Li, Sun, Tian, Luo, Ding, Gong and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroanatomy
Zhang, Jianping
Long, Ben
Li, Anan
Sun, Qingtao
Tian, Jiaojiao
Luo, Ting
Ding, Zhangheng
Gong, Hui
Li, Xiangning
Whole-Brain Three-Dimensional Profiling Reveals Brain Region Specific Axon Vulnerability in 5xFAD Mouse Model
title Whole-Brain Three-Dimensional Profiling Reveals Brain Region Specific Axon Vulnerability in 5xFAD Mouse Model
title_full Whole-Brain Three-Dimensional Profiling Reveals Brain Region Specific Axon Vulnerability in 5xFAD Mouse Model
title_fullStr Whole-Brain Three-Dimensional Profiling Reveals Brain Region Specific Axon Vulnerability in 5xFAD Mouse Model
title_full_unstemmed Whole-Brain Three-Dimensional Profiling Reveals Brain Region Specific Axon Vulnerability in 5xFAD Mouse Model
title_short Whole-Brain Three-Dimensional Profiling Reveals Brain Region Specific Axon Vulnerability in 5xFAD Mouse Model
title_sort whole-brain three-dimensional profiling reveals brain region specific axon vulnerability in 5xfad mouse model
topic Neuroanatomy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726261/
https://www.ncbi.nlm.nih.gov/pubmed/33324177
http://dx.doi.org/10.3389/fnana.2020.608177
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