Neurodegenerative markers in a perinatal asphictic model. Neuroprotection by estradiol

SARACENO, G. EZEQUIEL1; AYALA, M. V. 1; BADORREY, M. S. 1; HOLUBIEC, M. I. 1; AóN-BERTOLINO, M. L. 1; ROMERO, J. I. 1; KOLLIKER-FRERS R.A; GARCíA-SEGURA, L. M. 2; CAPANI, F.

Congreso; IBRO Congress; 2011

IBRO

Perinatal asphyxia (PA) is associated at short term with high morbidity and mortality and different long-term neurological diseases such as attention deficit disorder with hyperactivity, epilepsy, mental retardation, cerebral palsy, hearing and visual disturbances. In this work, we studied neurodegenerative markers in synaptic cytoskeleton in neurons and astrocytes in the stratum radiatum CA1 area of hippocampus at 30 days (mature synaptic contacts) and 120 days (adulthood) in a mouse model of PA. In addition, we observed the neuroprotective effects of late treatment with estradiol (daily dose of 250 ug / kg for 3 days). At 30 days after PA there were no significant differences between PA and CTL animals for microtubule-associated protein 2 (MAP2), the phosphorylation status of medium and heavy neurofilament (NFH / Mp) and glial fibrillary acidic protein (GFAP). However, there was an increase of mushroom type dendritic spines and actin cytoskeleton alterations, accompanied by M6a increased expression, a protein involved in spinogenesis. At 120 days we observed reactive gliosis (GFAP+) in PA animals, accompanied by morphological changes at MAP2+ dendrites level, as well as the NFH / M p. Estradiol late treatment reverted long term changes, associated with an increase in co localization of ERá receptor with GFAP + astrocytes. Moreover, western blot analyses showed a decrease of IGF-1 receptors in PA animals, which are recovered by estradiol late treatment. These data suggest that the damage caused by the PA are progressive, beginning with early changes at the actin cytoskeleton in mushroom type dendritic spines, extended into neurodegenerative changes with alterations in neurofilaments, the dendritic cytoskeleton and astrocytes. Late treatment with estradiol reverted the damage observed, possibly acting at non-genomic level by the pathway activation of ERá receptor associated with IGF-1 beta receptor.