Aging and Increased Hypothalamic Glial Fibrillary Acid Protein (GFAP) mRNA in F344 Female Rats

Abstract

During reproductive aging, female rodents show impaired inducibility of the estradiol (E2)-induced (preovulatory) surge of luteinizing hormone (LH), which is associated with hypothalamic neuronal impairments of aging. To evaluate if astrocytes show comparable age changes, we analyzed the regulation of glial fibrillary acidic protein (GFAP) mRNA which is transiently increased in the arcuate nucleus in association with the proestrus LH surge in young rats. In aging (18-month-old) F344 rats in persistent estrus, the loss of the E2-induced LH surge was paralleled by the lack of increased GFAP mRNA in the arcuate nucleus (in situ hybridization with X-ray film). We then tested the hypothesis that restoration of the LH surge by chronic ovariectomy (OVX) in aging rats would restore or block GFAP mRNA induction, respectively. Despite restoration of the inducible LH surge in aging rats by chronic OVX, there was no induction of GFAP mRNA in the arcuate nucleus. Moreover, young rats given chronic E2 implants for 6 weeks as a model for persistent estrus, retained induction of arcuate nucleus GFAP mRNA, despite loss of the induced LH surge. The aging rats were highly sensitive to gross pituitary enlargement from chronic E2 with 50% mortality; thus, the F344 genotype is not optimum for studies of aging-E2 interactions that require prolonged E2 treatments. More detailed cellular level analysis of GFAP mRNA is needed to define the relationship of GFAP expression to synaptic reorganization during the LH surge. The aging rats also showed higher levels of GFAP mRNA in the arcuate nucleus and ventromedial nucleus, consistent with the general trend for elevated GFAP mRNA during aging in other brain regions and in both sexes.