INVOLVEMENT OF STEROID HORMONES IN NEURODEGENERATIVE DISORDERS: LESSONS FROM ANIMAL MODELS.

ALEJANDRO F. DE NICOLA; LUCIANA PIETRANERA; JUAN BEAUQUIS; YANINA REVSIN; FLAVIA SARAVIA

Leiden, Holanda

Congreso; 37th Annual Conference of the International Society for Psychoneuroendocrinology; 2007

International Society for Psychoneuroendocrinology

In the brain, steroid hormones exert pleiotropic effects under normal and pathological conditions. Data obtained in animal models of diabetes mellitus, genetic (SHR) and mineralocorticoid hypertension and aging, demonstrated similar hippocampal abnormalities and changes of adrenal steroid function pointing to a glucocorticoid or mineralocorticoid overdrive. Changes of adrenal function included hypersensitive HPA axis, elevated levels of circulating steroids and / or increased receptor activity. Common findings in the hippocampus of the four disease models included: a) decreased progenitor proliferation in the subgranular zone (SGZ) of the dentate gyrus; b) astroglial reactivity, with increased expression of the glial fibrillary acidic protein (GFAP); c) decreased neuronal density in the hilus of the dentate gyrus. Changes were reversible by treatment with estrogens – prototype neuroprotective hormones – which ameliorated the hippocampal parameters. Thus, in models of diabetes, hypertension and aging, estradiol treatment stimulated progenitor proliferation in the SGZ, normalized the density of GFAP+ astrocytes, and recovered hilar cell number. The effects of adrenal steroids and estrogens on hippocampal markers support a dual role for steroid hormones in the susceptibility to neurodegenerative diseases.