Activation of hippocampal microglia with aging. Immunohistochemical co-localization of the microglia-specific marker Iba1 and the activation-specific marker CD74 (MHC II invariant chain) identified an increase in activated microglia in the aged hippocampus regardless of cognitive status. In adults, Iba1+ microglia were distributed throughout hippocampal subregions, with a greater population evident in CA3 than in CA1 or DG. A small fraction of microglia exhibited mild activation indicated by low levels of CD74 immunoreactivity. In both aged cognitively intact and aged cognitively impaired rats, a marked increase in the number of Iba1+/CD74+ microglia was observed in all three subregions, in the form of both mildly-activated and moderately-activated microglia. Activated microglia were associated with both synaptic and cell body-containing hippocampal strata. Blue: Hoechst; Red: Iba1; Green: CD74; Orange: Iba1/weak CD74 co-expression (mild activation); Yellow: Iba1/high CD74 co-expression (moderate activation).