Differential activation of caspase-3 at two maturational stages during okadaic acid-induced rat neuronal death.

Okadaic acid (OA), a protein phosphatase inhibitor, is used as a research model of Alzheimer's disease to induce tau phosphorylation and neuronal death. We reported previously that OA induces neuronal apoptosis of immature neurons (in vitro days (IVD) 3-5), which is inhibited by cycloheximide (CHX). In this study, we demonstrate that CHX fails to prevent OA-induced neuronal death in mature neurons (IVD 14-15). Upon comparison of both types of dying cells, the immature neurons displayed characteristic features of apoptosis, such as nuclear fragmentation, phosphatidylserine externalization and prominent caspase-3 activation, while the mature neurons showed few characteristic features of apoptosis. Lack of the beneficial effects of CHX and the lesser activation of caspase-3 in the mature neurons argue against typical apoptotic neuronal death in the OA-induced neurodegeneration model.