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

Authors :
Jianping Zhang
Ben Long
Anan Li
Qingtao Sun
Jiaojiao Tian
Ting Luo
Zhangheng Ding
Hui Gong
Xiangning Li
Source :
Frontiers in Neuroanatomy, Vol 14 (2020), Frontiers in Neuroanatomy
Publication Year :
2020
Publisher :
Frontiers Media S.A., 2020.

Abstract

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.

Details

Language :
English
ISSN :
16625129
Volume :
14
Database :
OpenAIRE
Journal :
Frontiers in Neuroanatomy
Accession number :
edsair.doi.dedup.....a09d6f85edc435a222f196431da7030e
Full Text :
https://doi.org/10.3389/fnana.2020.608177/full