Amyloid-β1-40 differentially stimulates proliferation, activation of oxidative stress and inflammatory responses in male and female hippocampal astrocyte cultures

Abstract

Alzheimer's disease (AD) is the most common form of dementia and has a higher incidence in women. The main component of the senile plaques characteristic of AD is amyloid-beta (Aβ), with surrounding astrocytes contributing to the degenerative process. We hypothesized that the sex difference in the incidence of AD could be partially due to differential astrocytic responses to Aβ. Thus, the effect of Aβ_1-40 on cell viability, the inflammatory response, and oxidative status was studied in cultures of hippocampal astrocytes from male and female rats. Aβ_1-40 increased astrocyte viability in both female and male cultures by activating proliferation and survival pathways. Pro-inflammatory and anti-inflammatory responses were induced in astrocytes from both sexes. Aβ_1-40 did not affect endoplasmic reticulum stress although it induced oxidative stress in male and female astrocytes. Interestingly, male astrocytes had an increase in cell number and significantly lower cell death in response to Aβ_1-40. Conversely, astrocytes from females displayed a greater inflammatory response after the Aβ_1-40 challenge. These results suggest that the inflammatory and oxidative environment induced by Aβ_1-40 in female astrocytes may contribute to enhance the vulnerability to AD and warrants further studies to unveil the mechanisms underlying sex differences in astrocytic responses.

Keywords: Amyloid-beta; Astrocytes; Neuroinflammation; Oxidative stress; Proliferation.