Neuroprotective effects of estradiol in hippocampal neurons and glia of middle age mice
During aging the hippocampus experiences structural, molecular, and functional alterations. Protection from age-related disorders is provided by several factors, including estrogens. Since aging defects start at middle age, we studied if 17 β-estradiol (E2) protected the hippocampus at this age peri...
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| Autores principales: | , , , |
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| Formato: | JOUR |
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_03064530_v32_n5_p480_Saravia |
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| Sumario: | During aging the hippocampus experiences structural, molecular, and functional alterations. Protection from age-related disorders is provided by several factors, including estrogens. Since aging defects start at middle age, we studied if 17 β-estradiol (E2) protected the hippocampus at this age period. Middle age (10-12 month old) male C57Bl/6 mice were implanted sc with E2 (15 μg) or cholesterol pellets. Ten days afterwards they received bromodeoxyuridine (BrdU) 4 and 2 h before killing to study cell proliferation in the dentate gyrus (DG). A pronounced depletion of BrdU+cells in the DG was found in cholesterol-treated middle age mice, accompanied by astrocytosis, and by neuronal loss in the hilus. Middle age mice receiving E2 showed increased number of BrdU+cells while the other parameters were remarkably attenuated. When steroid treatment was prolonged for 2 months to study migration of cells in the granular layer of the DG, cell migration was unaffected by E2. However, E2-treated middle age mice presented higher cell density and increased staining for doublecortin, a marker for differentiating neurons. Thus, from the three basic steps of adult neurogenesis (proliferation, migration, and differentiation), E2 stimulated progenitor proliferation-even after long exposure to E2 studied by Ki67 immunocytochemistry-and differentiation towards a neuronal lineage. This result, in conjunction with recovery from other aging indicators as increased deposits of the aging pigment lipofuscin in DG cells, loss of hilar neurons and astrocytosis supports a wide range protection of hippocampal function of middle age mice by estrogenic hormones. © 2007 Elsevier Ltd. All rights reserved. |
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