Manipulations of ERs by cDNA and siRNA in astrocytes from adult male rats before coculture with E18 neurons, assayed as responses of astrocyte GFAP and E18 neurite outgrowth (MAP5) (4 cultures, 4 brains per age group). Data are expressed as percentage of respective age control (ctl) (mean ± SEM). ***P < .001; **P < .01; *P < .05. A, ERα-cDNA transfection of 3-month-old astrocytes increased GFAP 40% and decreased neurite outgrowth 50%. B, ERβ knockdown by siRNA in 3-month-old astrocytes increased GFAP 50% and decreased neurite outgrowth 50%. C, ERα knockdown by siRNA in 24-month-old astrocytes decreased GFAP 50%. D, ERα-cDNA transfection of 24-month-old astrocytes decreased GFAP 50%.