AGE-RELATED ACTIVATION OF MICROGLIA AND ASTROCYTES - IN-VITRO STUDIESSHOW PERSISTENT PHENOTYPES OF AGING, INCREASED PROLIFERATION, AND RESISTANCE TO DOWN-REGULATION

Astrocytes and microglia from cerebral cortex of 3-, 6-, 12-, and 24-m onth-old F344 male rat donors showed progressively greater proliferati on during primary culture. Microglia from aging donor brains exhibited an amoeboid-like morphology and express antigens characteristic of an activated state (e.g., major histocompatibility complex class Il). Mo reover, microglia from aging donors were less sensitive to several typ es of regulators. Granulocyte-macrophage colony stimulating factor sti mulated proliferation in microglia from young, but not aging brains. T ransforming growth factor (TGF)-beta 1 inhibited astrocytic and microg lial proliferation in cultures from young, but not aging donors. Simil arly, the inhibition of lipopolysaccharide-induced NO production by TG F-beta 1 in microglia was impaired in cultures from 12-month (middle-a ge) brains. Another aging change detected by middle age, increased gli al fibrillary acidic protein (GFAP) explosion, also persisted in astro cytes from 12- to 24-month-old brains, as evaluated by increased activ ity of a 5'-upstream GFAP promoter construct. Thus, both microglia and astrocytes originated from aging cerebral cortex maintain in vitro at least some of the activated phenotype of aging glia that an observed in vivo. This new in vitro cell model may allow efficient analysis of glial age changes. (C) 1998 Elsevier Science Inc.