Influence of Hypoglycemia on Subcellular Distribution of Phosphorylated Tau Threonine 181 and Phosphorylated Serine 199/202 within Hippocampal astrocytes

Background: The pathogenesis of Alzheimer's disease (AD) has a substantial focus on the buildup of beta-amyloid plaques (Aβ) and phosphorylated Tau protein tangles, in which astrocytes are involved in the clearance of these plaques and tangles. In addition, a large prospective study of type II diabetic patients that experienced hypoglycemia showed a significantly higher incidence of dementia. Furthermore, there was a significant linear association between increased frequency of hypoglycemia and an increased risk of dementia. Recently, studies have shown a correlation between early onset of type II diabetes and subsequent development of dementia. Method: In the current experiments, embryonic hippocampal rat astrocytes were cultured in complete media (high-glucose, electrolytes, and 10% fetal bovine serum (FBS). The incubator for cell cultures was maintained at 37 C, 95% humidity, until 85% confluent. The astrocytes were then resuspended in the above media or the same media with the glucose concentration reduced to 30%. Pterostilbene and sulforaphane was dissolved with Captisol® to increase their entry into the astrocytes. Visualizing tau microtubules in vitro was accomplished via utilization of antibodies specific to the tau protein and a Confocal Microscope. Experiments were performed to determine the possible altered distribution of phosphorylated tau at threonine 181(ptau181) and Ser199/Ser202 within the astrocytes. Result: The levels of phosphorylation of tau were higher in the cells containing lower concentrations of glucose. In addition, astrocytes exposed to low glucose showed higher levels of phosphorylated tau at threonine 181(ptau181) in subcellular fluid, while cells pretreated with low glucose showed higher levels of phosphorylated tau at Ser199/Ser202 in mitochondria and/or nuclei. Conclusion: The subcellular distribution of phosphorylated tau at threonine 181(ptau181) and Ser199/Ser202 within the astrocytes exposed to low glucose media was different.