Cellular and Molecular Neurobiology
Author: Azul Aymará Millán | Email: azulmillan@hotmail.com
Azul Aymará Millán1°, Matías Monteverde Busso1°,Camila Vidos1°, Alberto Javier Ramos1°, Alejandro Villarreal1°2°
1° Instituto de Biología Celular y Neurociencia “Prof. E. De Robertis” UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
2° Instituto Tecnológico de Buenos Aires (ITBA).
Astrocytes respond to brain injury through a process of reactive astrogliosis involving transcriptional, phenotypic and functional changes, with an impact on brain injury outcome. We aimed here to address early changes in astrocyte response as a result of hypo-osmolar stress promoted by brain edema. In a model of brain cortical injury adult Wistar rats we observed, using immunofluorescence, a higher proportion of astrocytes with lower levels of H3K9ac at 3.5h when compared to non-injured hemisphere. Also, the injury promoted an increase in GFAP and AQP4 immunoreactivity near the injury core suggesting edema formation. In vitro, exposure of astrocyte primary cultures to hypotonic (20, 30 and 40% osm) stress, significantly decreased the levels of H3K9ac and H3K27ac after 1 and 3h, which were restored to control values 24h after recovery in complete isotonic medium. The decrease in histone acetylation was prevented by histone deacetylase inhibitor Trichostatin-A. Astrocytes exposed to hypo-osmolar stress and bacterial liposaccharide (LPS) showed impaired NFkB (p65 subunit) nuclear translocation but no changes in gene expression. Interestingly, astrocyte number was reduced after hypo-osmolar stress. Our results suggest that astrocytes exposed to edema-like microenvironment show impaired global histone acetylation and response to pro-inflammatory stimulus LPS. These are evidences of mechanisms involved in astrocyte early response to injury which might condition injury progression.