Raloxifene neutralizes the adverse effects of glutamate on cultured neurons by regulation of calcium oscillations

Abstract

Calcium dyshomeostasis is an important pathology of memory impairment. However, the mechanism of how calcium dyshomeostasis impairs neurons has remained elusive. The aim of the present study was to reveal the influence of calcium dyshomeostasis on the expression of calcium memory-associated proteins and the ability of raloxifene to neutralize the adverse effects of glutamate on cultured neurons by regulation of calcium oscillations. After neurons were treated with various concentrations of glutamate alone or with raloxifene, the expression of calcium memory-associated proteins and the influence on calcium dyshomeostasis was assessed. The results indicated that glutamate regulated calcium oscillation waves and expression of calcium memory-associated protein in a concentration-dependent manner. Raloxifene increased the expression of these proteins as well as neuronal survival. It is therefore concluded that glutamate regulated calcium oscillations in a dose-dependent manner, while raloxifene protected neurons from destruction through glutamate exposure and at the same time neutralized the decrease in expression of the memory-associated proteins.