Influence of Dehydroepiandrosterone on Tau Hyperphosphorylation in Rat Hippocampal AstrocytesAlzheimer's Association International Conference 2018 (2018)
Background: Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy share a pathological mechanism of tau aggregation in neuronal cells and glial cells. Tau aggregates are reported to be hyperphosphorylated and associated with the pathological symptoms seen in neurodegenerative diseases. Dehydroepiandrosterone (DHEA) is a hormone released throughout life, in a similar amount to cortisol, until release decreases with age and is possibly associated with neurodegenerative diseases. The anti-inflammatory effects of DHEA make it a potential therapeutic agent for use in cytotoxic environments. The current study examines the effect of DHEA by comparing the levels of hyperphosphorylated tau in the absence and presence of DHEA. Methods: E18 rat hippocampal astrocytes were isolated and plated with DMEM (4.5 mg/ml D-glucose) + 10% fetal bovine serum. At 85% confluency, cells were trypsinized with 0.25% EDTA and re-plated in media which contained low concentration of D-glucose (1.35 mg/ml) to create stress. After incubation at 24 and 48 hours with DHEA (2mg/ml) and 30 minutes with 50 mM potassium chloride, an ELISA kit quantitatively measured levels of hyperphosphorylated tau via immunofluorescence. A Cell Counting Kit-8 (CCK-8) was used to determine cell viability by adding 10% volume per well of CCK-8 reagent. The plate was incubated at 37°C for one hour and absorbance read at 450nm. Results: CCK-8 showed high levels of glucose (4.5 mg/ml) produced greater cell viability than the stress condition (glucose at 1.35 mg/ml). ELISA immunofluorescence detected increased levels of hyperphosphorylated tau in conditions with low glucose. Exposure to DHEA decreased fluorescence readings in the tau ELISA (read at 450 nm). Conclusions: In the stress condition, exposure to DHEA was associated with decreased immunofluorescence due to hyperphosphorylated tau protein. In the experimental condition of increased stress induced via glucose manipulation in growth media, DHEA may have a cytoprotective role in these rat hippocampal astrocyte cells.
Publication DateJuly, 2018
Citation InformationJade McLain and Harry Komiskey. "Influence of Dehydroepiandrosterone on Tau Hyperphosphorylation in Rat Hippocampal Astrocytes" Alzheimer's Association International Conference 2018 (2018)
Available at: http://works.bepress.com/harry_komiskey/5/