INVESTIGADORES
SARAVIA Flavia Eugenia
artículos
Título:
Steroid protection in aging and age-associated diseases.
Autor/es:
AF DE NICOLA, PIETRANERA L, BEAUQUIS J, FERRINI M, SARAVIA F.
Revista:
EXPERIMENTAL GERONTOLOGY
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Año: 2009 vol. 44 p. 34 - 40
ISSN:
0531-5565
Resumen:
Neuroactive steroids are secretory products of peripheral endocrine glands that modulate a variety of
brain functions. A close relationship between neuroactive steroid structure and function becomes most
evident under pathological circumstances. On one side, overproduction of glucocorticoid and mineralocorticoid
neuroactive steroids may be detrimental to the hippocampus, which is enriched in glucocorticoid
receptors (GR) and mineralocorticoid receptors (MR). Thus, a dysfunction of the adrenocortical
system in aging and age-associated diseases (diabetes, hypertension) is able to cause hippocampal damage.
Whereas aging and uncontrolled diabetes show a predominant GR overdrive, a MR overdrive characterizes
hypertensive animals. Some abnormalities commonly found in the hippocampus of aging,
diabetic and hypertensive animals include decreased neurogenesis, astrogliosis and neuronal loss in
the hilus of the dentate gyrus (DG). On the other side, and in contrast to adrenal gland-derived steroids,
estrogens qualify as hippocampal neuroprotectants. Given to middle-age mice, estrogens stimulated proliferation
and differentiation of newborn cells in the DG, decreased astrogliosis and increased hilar neuronal
number. Similar estrogen effects were obtained in mice with streptozotocin-induced diabetes and
in spontaneously hypertensive rats (SHR). The results suggest that in aging and age-associated diseases,
adrenocortical steroid overdrive sensitizes the hippocampus to the pathological milieu imposed by a preexisting
degeneration or illness. In this setting, estradiol neuroprotection rescues hippocampal parameters
previously altered by the pathological environment