Alzheimer-associated presenilin 2 gene is dysregulated in rat medial temporal lobe cortex after complete brain ischemia due to cardiac arrest

Abstract

Background: Brain ischemia may be causally related with Alzheimer's disease. Probably, presenilin gene dysregulation may be associated with Alzheimer's disease neuropathology. Consequently, we have examined quantitative changes in both presenilin 1 and 2 genes in the medial temporal lobe cortex following 10-min global brain ischemia in rats.

Methods: Global brain ischemia was induced by cardiac arrest in female rats that were allowed to survive for 2, 7 and 30 days. The expression of presenilin genes was evaluated in the rat medial temporal lobe cortex with the use of quantitative RT-PCR analysis.

Results: Presenilin 1 gene expression tended to be downregulated from days 2 to 7 postischemia but at day 30, there was a reverse tendency. The greatest overexpression of presenilin 2 gene was noted at 2-nd day whilst on day 7, the expression of this gene was only modestly elevated. Eventually, at day 30 expression of presenilin 2 gene was modestly downregulated. Alterations of presenilin 2 gene expression between 2 and 7 days and between 2 and 30 days were statistically significant.

Conclusions: Thus, presented changes suggest that the significant dysregulation of presenilin 2 gene may be connected with a response of neuronal cells to transient global brain ischemia due to cardiac arrest. Finally, the ischemia-induced gene dysregulation may play a key role in the late onset of Alzheimer's-type dementia.

Keywords: Alzheimer's disease; Brain ischemia; Presenilin 1 and 2; Temporal cortex; γ-Secretase.