High-Dose Photodynamic Therapy Increases Tau Protein Signals in Drosophila

Detection and evaluation of tau proteins (Tau) and fibrillary tangles has been a focus in the field of neurodegeneration (ND) due to the high correlation with pathogenesis. Here, a novel approach is being proposed and developed to induce and assess those diseases. Photodynamic therapy (PDT) is applied to the wild-type fruit fly
Drosophila melanogaster
as a model of systemic oxidative stress to induce Tau accumulation. Excised brains are evaluated by Brillouin-Raman spectroscopy and microscopy with UV surface emissions (MUSE) to interrogate physical property changes due to fixation and high-dose PDT. MUSE reveals a small change in autofluorescence, particularly for females, with significant signal in both sexes once stained. A presence of significant mechanical changes in fresh brains treated with PDT compared to healthy controls is revealed using Brillouin spectroscopy. Enhanced Tau presence was confirmed with FSB staining and confocal analysis, with female test flies yielding nearly four-fold the mean intensity of controls, thus marking PDT as a potential neurodegenerative disease model. MUSE may serve as a viable early screening method and quantification in a research setting. This reduces the time for sample preparation and drastically decreases the cost of Tau evaluation.