Mechanisms of the spatial memory deficits induced by injection of okadaic acid into the Meynert nucleus basalis of rats

Abstract

We previously reported that the injection of okadaic acid (OA) into the Meynert nucleus basalis of rats induced spatial memory deficits. The present study was designed to further explore the underlying mechanisms. We found that the level of acetylcholine (Ach) in the hippocampus significantly decreased 24 h after injection of OA into the Meynert nucleus basalis of rats. Simultaneously, spatial memory deficit, PP-2A inhibition and tau hyperphosphorylation at Ser-198/Ser-199/Ser-202 (Tau-1 epitope) and Ser-396/Ser-404 (PHF-1 epitope) were observed. With the restoration of hippocampus Ach to normal levels at 48 and 72 h after the injection, the spatial memory deficits, PP-2A inhibition and tau hyperphosphorylation were reversed. It is suggested that injection of OA into the Meynert nucleus basalis of rats may impair the hippocampus-dependent spatial memory through damaging the cholinergic projection between the Meynert nucleus basalis and the hippocampus and the selective inhibition of PP-2A and tau hyperphosphorylation may be at least part of the underlying mechanisms.

Keywords

protein phosphatase 2 / tau proteins / phosphorylation / hippocampus / acetylcholine