Effect of B-Amyloid Protein and IFN-r on Activation of Microglia

Abstract

The senile plaques characteristic of aging and Alzheimer's disease in brain tissue are composed of insoluble aggregates of β-amyloid protein, and infiltrated by reactive microglia. The rote of microglia in neuronal damage is not fully understood. It has been suggested that immune responses may lead to damage of brain tissue. The fact that microglia express MHC class Ⅰ and Ⅱ molecules suggests that they are able to process protein antigens and present the antigen peptides to T lymphocytes. Thus, the microglia that are the resident macrophages In brain tissue are able to participate in induction of immune responses in the brain. lt has been reported that the activated microglial cells produce reactive nitrogen intermediates such as nitric oxide and hydrogen peroxide, which lead to damage of brain tissue. In this study, we examine whether rat microglial cells produce nitric oxide upon Stimulation with active fragment of β-amyloid protein(25-35 amino adds). The results indicate that β-amyloid alone does not stimulate microglia to produce nitric oxide. However, we observed an enhancing effect of β -amyloid and IFN-r in triggering the production of nitric oxide by microglial culture. In addition, IFN- γ potentiates a synergistic effect with LPS on the production of nitric oxide in microglial culture. These findings suggest that β -amyloid activates microglial cells in the presence of IFN-γ, and this may have a role in the pathogenesis of neuronal degeneration observed in aging and Alzheimer's disease.