Development of therapies based on neuroactive steroids and neurosteroids for the treatment of experimental neuropathologies

DE NICOLA AF.; BEAUQUIS J; CORONEL F; GARAY L; GONZALEZ DENISELLE M.C; GONZALEZ SL; LABOMBARDA F; PIETRANERA L; SARAVIA F; MEYER M; GARGIULO MONACHELLI G,; BROCCA E; VAN OVERVELD L; LIMA A; ROIG P

ACTA BIOQUíMICA CLíNICA LATINOAMERICANA

FEDERACION BIOQUIMICA PROVINCIA BUENOS AIRES

Lugar: La Plata; Año: 2011 p. 94 - 99

0325-2957

Steroids showing activity on the nervous system are known as “neuroactive steroids”. They exert neuroprotective or neurotoxic activities, depending on their chemical structure, circulating or tissue concentrations, binding to different receptors and the mechanisms of intracellular signalling employed. In order to elucidate these properties, we worked with animal models of human neuropathologies, including spinal cord injury, neuropathic pain, multiple sclerosis, and amyotrophic lateral sclerosis. In these models, treatment with progesterone has shown great therapeutic effectiveness. In another set of studies, we have shown that hypertensive animals bear a pronounced encephalopathy, possible caused by an overdrive of the mineralocorticoid system. We have suggested that overdrive of the mineralocorticoid system plays a neurotoxic role, based on the development of a similar brain abnormalities following mineralocorticoid treatment of otherwise normal animals. The encephalopathy of hypertension is similar to that developed by diabetes mellitus and aging animals. In the three cases, estrogen treatment provided strong neuroprotection, as shown by enhanced hippocampal neurogenesis, increased neurotrophic factor expression and decreased astrogliosis. Thus, the use of estrogens supports the regenerative capacity and plasticity of the nervous system. Therefore, animal models become useful tools for transfer in the short-term of experimental data to the human patient.