Astrocytic reaction to a lesion, under hormonal deprivation.
Gonadal hormones can influence the morphology and function of glial cells, particularly astrocytes. Here we explore the hypothesis that 17beta-estradiol (E2) exerts a positive effect on astrocytes within the region of the cholinergic neurons of the basal forebrain, an area heavily implicated in memory and attentional processes. Female rats were ovariectomized at 3 months of age and lesioned with the immunotoxin 192 IgG-saporin before receiving a subcutaneous pellet containing 0.25mg of estrogen or placebo, released over 60 days. The control, non-ovariectomized group was treated identically. At the end of the treatment, we used image analysis procedures to evaluate changes in the levels of glial fibrillary acidic protein (GFAP) expression in the area of the lesion. Infusion of the immunotoxin induced a slight increase in GFAP expression in some subjects, compared to the contralateral side. However, when differences within animals where factored in, GFAP expression in ovariectomized animals treated with E2 was undistinguishable from intact controls. By contrast, in ovariectomized animals treated with placebo, GFAP expression was significantly higher. These results suggest that E2 deprivation may exacerbate the effects of an immunotoxic lesion, and, more importantly, that E2 administration may contribute to structural recovery of lesioned cholinergic neurons by blocking GFAP expression in the area. These results are particularly relevant in the context of female aging and postmenopausal dementia, and further highlight other potential levels at which to design interventions to preserve an intact cholinergic system, which may be crucial to prevent Alzheimer's disease.
Martinez
Lizeth
L
Department of Biomedical Sciences, Charles R. Drew University of Medicine and Sciences, 1731 East 120th Street, Los Angeles, CA 90059, USA.
de Lacalle
Sonsoles
S
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000922:Immunotoxins / Q000633:toxicity; D009699:N-Glycosyl Hydrolases / Q000633:toxicity; D010052:Ovariectomy; D016548:Prosencephalon / Q000293:injuries* / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D005904:Glial Fibrillary Acidic Protein; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D004958:Estradiol; D009699:N-Glycosyl Hydrolases; D000076985:Saporins