Steroid protection in aging and age-associated diseases

DE NICOLA, ALEJANDRO F.; PIETRANERA, LUCIANA; BEAUQUIS, JUAN; FERRINI, MÓNICA; SARAVIA, FLAVIA

EXPERIMENTAL GERONTOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2009 vol. 44 p. 34 - 40

0531-5565

Neuroactive steroids are secretory products of peripheral endocrine glands that modulate a variety ofbrain functions. A close relationship between neuroactive steroid structure and function becomes mostevident under pathological circumstances. On one side, overproduction of glucocorticoid and mineralocorticoidneuroactive steroids may be detrimental to the hippocampus, which is enriched in glucocorticoidreceptors (GR) and mineralocorticoid receptors (MR). Thus, a dysfunction of the adrenocorticalsystem 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 characterizeshypertensive animals. Some abnormalities commonly found in the hippocampus of aging,diabetic and hypertensive animals include decreased neurogenesis, astrogliosis and neuronal loss inthe 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 proliferationand differentiation of newborn cells in the DG, decreased astrogliosis and increased hilar neuronalnumber. Similar estrogen effects were obtained in mice with streptozotocin-induced diabetes andin 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 preexistingdegeneration or illness. In this setting, estradiol neuroprotection rescues hippocampal parameterspreviously altered by the pathological environment.