P1‐336: Hypoglycemia induces tau hyperphosphorylation and learning and memory deficit in Wistar rats

Several lines of evidence indicate that cerebrovascular diseases and subsequent cerebral hypoperfusion are intimately associated with the onset of AD. Brain hypoperfusion leading to disturbed brain glucose and energy metabolism can be resolved by brain imaging and is routinely used to assist clinical diagnosis of AD. The objective of this study is to examine the effect of hypoglycemia on AD-related pathology and learning and memory performance. Neuroblastoma cells, N2a, were cultured in glucose-deficient medium and the levels of tau and Aβ were determined. To create a hypoglycemia model, streptozotocin (STZ), a glucose analog that selectively injury glucose transporter type II bearing cells, was injected into lateral ventricle of adult male Wistar rat. In the CNS, glucose transporter type II bearing cells are expressed predominantly in the astrocytes of the limbic cortex including hippocampus and entorhinal cortex. An injury to the astrocyte would hinder the transport of glucose from circulation to neuron. In the glucose-deficient treated N2a cells, the levels of p-AMPK, a sensor for energy deficiency, were increased. The levels of p-Akt, p-GSK-3β, total tau and p-tau were also increased in the glucose-deficient cells. However, the levels of APP and Aβ were unaltered. In the STZ-treated rats, astrogliosis was evident in hippocampus and nearby cortex. The levels of p-AMPK, Akt, p-GSK-3β, hyperphosphorylated tau were increased in the hippocampus, but not in the cortex. The levels of APP and Aβ were not changed in either region. Furthermore, the learning and memory performance was greatly affected by the treatment of STZ. Hypoglycemia induces tau-, but not the Aβ-, related pathology.