Docosahexaenoic acid (DHA) consumption reduces spatial memory impairment in mice carrying the human
apolipoprotein E ε4 (
APOE4) allele. The current study evaluated whether astrocyte and microglia morphology contribute to the mechanism of this result.
APOE3 and
APOE4 mice were fed either a DHA-enriched diet or a control diet from 4 to 12 months of age. Coronal brain sections were immunostained for GFAP, Iba1, and NeuN. Astrocytes from
APOE4 mice exhibited signs of reactive
astrogliosis compared to
APOE3 mice. Consumption of DHA exacerbated reactive astrocyte morphology in
APOE4 carriers. Microglia from APOE4-control mice exhibited characteristics of amoeboid morphology and other characteristics of ramified morphology (more processes, greater process complexity, and greater distance between neighboring microglia). DHA enhanced ramified microglia morphology in
APOE4 mice. In addition,
APOE4 mice fed the DHA diet had lower hippocampal concentrations of
interleukin-7,
lipopolysaccharide-induced
CXC chemokine and
monocyte chemoattractant protein 1, and higher concentration of
interferon-gamma compared to APOE4-control mice. Our results indicate that a diet rich in DHA enhances reactive
astrogliosis and ramified microglia morphology in
APOE4 mice.