Effects of age on gene expression during estrogen-induced synaptic sprouting in the female rat

Age and estrogen treatment influenced fiber outgrowth and compensatory neur onal sprouting after unilateral entorhinal cortex lesions (ECL) which model Alzheimer disease-like deafferentation in the dentate gyrus of the hippoca mpus, In young F344 rats (3 months old), ovariectomy (OVX) decreased reacti ve fiber outgrowth by 60%. Sprouting in middle-aged rats (18 months old) wa s reduced in intact females; no further reduction was caused by OVX, Severa l astrocyte mRNAs were measured in the dentate gyrus of young and middle-ag ed female rats in three different estrogen states (sham OVX, OVX, or OVX estradiol) 1 week after ECL, Glial fibrillary acidic protein (GFAP) mRNA wa s twofold greater in middle-aged rats than young, although both ages showed threefold increases in response to ECL, In prior studies GFAP was found to be decreased by estradiol treatment 3-4 days after ECL; in this study GFAP mRNA had returned to sham OVX levels in young rats by 7 days post-ECL, Sur prisingly, estradiol treatment increased GFAP mRNA levels by 25% above OVX in middle-aged rats. Apolipoprotein E (apoE) mRNA was decreased 20% by age in the dentate, although both age groups showed a 25% increase in apoE mRNA in response to ECL. Apolipoprotein J (apoJ) mRNA was increased 20% in the dentate gyrus of middle-aged rats, and both age groups responded to ECL wit h a 65% increase in apoJ mRNA. The estrogen state did not alter levels of e ither apolipoprotein mRNA in the deafferented dentate. The data suggest tha t the estrogen-induced decrease of GFAP in response to lesions does not per sist at 7 days post-ECL during sprouting, Overall effects of age on the den tate gyrus include elevated GFAP mRNA and decreased apoE mRNA. The cortical wound site showed consistent enhancement of GFAP mRNA in both age groups b y estradiol above sham OVX and greater responses in middle-aged rats. (C) 2 000 Academic Press.