Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783620845234552832 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7726261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhangjianping wholebrainthreedimensionalprofilingrevealsbrainregionspecificaxonvulnerabilityin5xfadmousemodel AT longben wholebrainthreedimensionalprofilingrevealsbrainregionspecificaxonvulnerabilityin5xfadmousemodel AT lianan wholebrainthreedimensionalprofilingrevealsbrainregionspecificaxonvulnerabilityin5xfadmousemodel AT sunqingtao wholebrainthreedimensionalprofilingrevealsbrainregionspecificaxonvulnerabilityin5xfadmousemodel AT tianjiaojiao wholebrainthreedimensionalprofilingrevealsbrainregionspecificaxonvulnerabilityin5xfadmousemodel AT luoting wholebrainthreedimensionalprofilingrevealsbrainregionspecificaxonvulnerabilityin5xfadmousemodel AT dingzhangheng wholebrainthreedimensionalprofilingrevealsbrainregionspecificaxonvulnerabilityin5xfadmousemodel AT gonghui wholebrainthreedimensionalprofilingrevealsbrainregionspecificaxonvulnerabilityin5xfadmousemodel AT lixiangning wholebrainthreedimensionalprofilingrevealsbrainregionspecificaxonvulnerabilityin5xfadmousemodel |