Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain.
Journal
eLife
Series/Report No.
eLife
Journal Volume
13
ISSN
2050-084X
Date Issued
2024-05-22
Author(s)
Lin, Ya-Hui
Wang, Li-Wen
Chen, Yen-Hui
Chan, Yi-Chieh
Hu, Shang-Hsiu
Wu, Sheng-Yan
Chiang, Chi-Shiun
Huang, Guan-Jie
Yang, Shang-Da
Chu, Shi-Wei
Lin, Chin-Hsien
Cheng, Hwai-Jong
Chen, Bi-Chang
Chu, Li-An
DOI
10.7554/eLife.93212
Abstract
Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.
Subjects
FFPE
archived tissues
human
mouse
multiplexed staining
neuroscience
tissue clearing
whole brain analysis
whole mouse brain imaging
SDGs
Publisher
eLife Sciences Publications, Ltd
Type
journal article