Abstract
.Disruptions and alterations to cerebral energy metabolism play a vital role in the onset and progression of many neurodegenerative disorders and cerebral pathologies. In order to precisely understand the complex alterations underlying Alzheimer’s disease (AD) progression, in vivo imaging at the microscopic level is required in preclinical animal models. Utilizing two-photon fluorescence lifetime imaging microscopy and the phasor analysis method, we have observed AD-related variations of endogenous fluorescence of reduced nicotinamide adenine dinucleotide (NADH) in vivo. We collected NADH FLIM images from the cerebral cortices of both APPswe:PS1dE9 mice to model amyloid plaque accumulation and corresponding age-matched wildtype controls. Distinct variations in NADH fluorescence lifetime between wildtype and AD mice, as well as variations related to proximity from amyloid plaques, are obvervable via the phasor method. The combination of NADH FLIM and phasor analysis allows for a minimally invasive, high-resolution technique to characterize the adverse effects of amyloid accumulation on mitochondrial energy metabolism and could guide our understanding of preclinical AD pathology.
Highlights
Alzheimer’s disease (AD) is a devastating neurodegenerative disease with rapidly increasing incidence
We previously demonstrated that phasor analysis of endogenous NADH fluorescence can robustly detect pharmacologically induced alterations in mitochondrial energy metabolism.[30]
Similar to flavin adenine dinucleotide (FAD), NADH is endogenous and ubiquitous within most eukaryotic cells, and it participates in multiple steps of glucose breakdown and ATP synthesis
Summary
Alzheimer’s disease (AD) is a devastating neurodegenerative disease with rapidly increasing incidence. We apply two-photon fluorescence lifetime imaging microscopy (2P-FLIM) of endogenous cortical NADH for minimally invasive characterization of AD-induced variations in cerebral metabolism in a mouse model of AD.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.