title: Differential effects of estrogen in the injured forebrain of young adult and reproductive senescent animals.
abstract: Estrogen attenuates neural damage resulting from a variety of experimental injury models in adult female rats. To determine whether estrogens neuroprotective actions are age-specific, the present study compared the effects of estrogen on young adult and reproductive senescent animals subject to excitotoxic injury to the forebrain. NMDA was injected bilaterally into the olfactory bulbs of estrogen and placebo-replaced young adult and reproductive senescent animals. Lysates of the olfactory bulb and its basal forebrain afferent, the horizontal limb of the diagonal band of Broca (hlDBB), harvested 24h later were analyzed for expression of IL-1beta, IL-10, and nerve growth factor (NGF). NMDA injections resulted in local activation of microglia and an increase in IL-1beta. Estrogen replacement decreased IL-1beta expression in young adult females, but paradoxically enhanced its expression in reproductive senescent females. Furthermore, bulb injury increased IL-1beta production in the hlDBB of reproductive senescent animals although estrogen replacement was able to suppress lesion-induced expression of this cytokine. In both, the olfactory bulb and hlDBB, constitutive expression of the anti-inflammatory cytokine IL-10 was significantly higher while that of NGF was almost 50% lower in senescent animals as compared to young adults, indicating that aging preferentially altered Th2-type secretions. The present findings are consistent with our earlier observations that estrogen does not exert trophic effects in the aging forebrain and supports the hypothesis that estrogen treatment to reproductive senescent females may exacerbate neural injury.
authors.affiliation: Department of Human Anatomy and Medical Neurobiology, Texas A&M University System, Health Science Center, 228 Reynolds Medical Building, College Station, TX 77843-1114, USA.
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Nordell
authors.forename: M Melissa
authors.initials: MM
authors.lastname: Scarborough
authors.forename: Angela K
authors.initials: AK
authors.lastname: Buchanan
authors.forename: Farida
authors.initials: F
authors.lastname: Sohrabji
mesh_terms: D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D020667:Diagonal Band of Broca / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015914:Estrogen Replacement Therapy / Q000379:methods; D004967:Estrogens / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D016202:N-Methylaspartate / Q000633:toxicity; D020932:Nerve Growth Factor / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy / Q000379:methods; D016548:Prosencephalon / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D051381:Rats; D012098:Reproduction / Q000502:physiology*
chemical_list: D004967:Estrogens; D018690:Excitatory Amino Acid Agonists; D007375:Interleukin-1; D037102:Lectins; D016753:Interleukin-10; D016202:N-Methylaspartate; D020932:Nerve Growth Factor