INVESTIGADORES
SARAVIA Flavia Eugenia
capítulos de libros
Título:
Involvement of Neuroactive Steroids in Hippocampal Disorders: Lessons from Animal Models.
Autor/es:
DE NICOLA AF, PIETRANERA L, BEAUQUIS J, HOMO-DELARCHE F, SARAVIA F
Libro:
Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders
Editorial:
Springer
Referencias:
Año: 2008; p. 61 - 87
Resumen:
Steroids secreted from peripheral endocrine glands and acting on the brain are
called neuroactive steroids. Under physiological conditions, neuroactive steroids
modulate multiple brain functions, and in aging, trauma or neurodegeneration their role
varies from neuroprotective to neurotoxic depending on the chemical properties of the
steroid. In this regard, it is known that excess levels of adrenal steroids (gluco and
mineralocorticoids) sensitize the hippocampus to the deleterious effects of a
pathological environment, whereas the sex hormone estradiol is a powerful
hippocampal neuroprotectant. We studied the protective role of estrogens in the ailing
hippocampus in animal models of aging and age-associated diseases such as diabetes
mellitus and hypertension of genetic (SHR) or mineralocorticoid origin. These models
present in common a glucocorticoid or mineralocorticoid overdrive, a process that
exacerbates hippocampal neuropathology, according to: 1) decreased proliferation of
neuronal progenitors in the subgranular zone (SGZ) of the dentate gyrus (DG); 2)
astroglial reactivity, with increased expression of the glial fibrillary acidic protein
(GFAP), and 3) decreased neuronal density in the hilus of the DG. These pathological
changes were reversible by treatment with estrogens, which ameliorated the
hippocampal parameters in middle age mice and models of diabetes and hypertension.
Thus, estradiol treatment stimulated progenitor proliferation in the SGZ, normalized the
density of GFAP+ astrocytes, and avoided the loss of hilar neurons. Given the
important role of the hippocampus in learning, memory and neuroendocrine events,
estrogens may offer therapeutic advantages for the treatment of brain disturbances
accompanying systemic diseases and aging.