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Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy


Ni, Ruiqing; Chen, Zhenyue; Gerez, Juan A; Shi, Gloria; Zhou, Quanyu; Riek, Roland; Nilsson, K Peter R; Razansky, Daniel; Klohs, Jan (2020). Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy. Biomedical Optics Express, 11(9):4989.

Abstract

Current intravital microscopy techniques visualize tauopathy with high-resolution, but have a small field-of-view and depth-of-focus. Herein, we report a transcranial detection of tauopathy over the entire cortex of P301L tauopathy mice using large-field multifocal illumination (LMI) fluorescence microscopy technique and luminescent conjugated oligothiophenes. In vitro assays revealed that fluorescent ligand h-FTAA is optimal for in vivo tau imaging, which was confirmed by observing elevated probe retention in the cortex of P301L mice compared to non-transgenic littermates. Immunohistochemical staining further verified the specificity of h-FTAA to detect tauopathy in P301L mice. The new imaging platform can be leveraged in pre-clinical mechanistic studies of tau spreading and clearance as well as longitudinal monitoring of tau targeting therapeutics.

Abstract

Current intravital microscopy techniques visualize tauopathy with high-resolution, but have a small field-of-view and depth-of-focus. Herein, we report a transcranial detection of tauopathy over the entire cortex of P301L tauopathy mice using large-field multifocal illumination (LMI) fluorescence microscopy technique and luminescent conjugated oligothiophenes. In vitro assays revealed that fluorescent ligand h-FTAA is optimal for in vivo tau imaging, which was confirmed by observing elevated probe retention in the cortex of P301L mice compared to non-transgenic littermates. Immunohistochemical staining further verified the specificity of h-FTAA to detect tauopathy in P301L mice. The new imaging platform can be leveraged in pre-clinical mechanistic studies of tau spreading and clearance as well as longitudinal monitoring of tau targeting therapeutics.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Institute of Biomedical Engineering
Dewey Decimal Classification:170 Ethics
610 Medicine & health
Scopus Subject Areas:Life Sciences > Biotechnology
Physical Sciences > Atomic and Molecular Physics, and Optics
Uncontrolled Keywords:Biotechnology, Atomic and Molecular Physics, and Optics
Language:English
Date:1 September 2020
Deposited On:16 Feb 2021 12:40
Last Modified:17 Feb 2021 21:01
Publisher:Optical Society of America
ISSN:2156-7085
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1364/boe.395803
PubMed ID:33014595
Project Information:
  • : FunderSNSF
  • : Grant ID320030_179277
  • : Project TitleInvestigating the effects of hypercholesterolemia on neutrophil-mediated thromboinflammation after cerebral ischemia

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