Histone acetylation in reactive astrocytes: Is microglia the triggering ?sparkle??

MONTEVERDE M; RAMOS AJ; VIDOS C; VILLARREAL A ; CIERI MB

Congreso; Reunion Anual de la Sociedad Argentina de Investigacion en Neurociencias 2018; 2019

Astrocytes are essential in keeping CNS homeostasis and bringing metabolic support to neurons. It was shown that microglia activated by Lipopolysaccharide (LPS) promotes astroglial polarization to the pro-inflammatory and neurotoxic phenotype A1. We showed that this polarization is TLR4/NFκB dependent (Rosciszewski et al., 2018). In different peripheral cell types, NFκB can recruit enzymes with chromatin remodelling functions (e.g. histone acetyltransferase p300). We here aimed to understand if NFκB activation primes chromatin in A1 astrocytes through histone acetylations.We used primary cultures of glial cells obtained from C57BL/6 mice. After microglia depletion, cultures were exposed to LPS 25ng/ml for different times. NFκB activation and histone 3 acetylation (H3ac) was evaluated by immunofluorescence and immunoblotting. Astrocyte or microglia were identified as GFAP+ or IBA1+ cells respectively. Nuclear localization of NFκB subunit p65 was used as parameter of activation.Our results show that NFκB is activated in astrocytes at 1 h LPS (not before) remaining active for at least 6 h. Activation at 1 h significantly increased when microglia was added to cultures. However, we were not able to detect global changes in H3ac after LPS exposure in microglia-depleted primary cultures of astrocytes. We conclude that microglial cells may be the key to induce chromatin remodelling by facilitating NFκB activation.Supported by UBACYT, PICT 2017-2203, PICT 2015-1451, PIP Conicet