In vitro modeling of the broad spectrum of astrogliosis

MURTA V, SEKHAR MANNAVA R, SCHILRREFF P, MORRILLA MJ, RAMOS AJ

Congreso; XXX Congreso de la Sociedad Argentina de Investigacion en Neurociencias (SAN); 2015

Astrocytes are complex, highly heterogenic cells found throughout the CNS, which makenumerous contributions to normal function in healthy CNS. Their broad spectrum ofactivation profiles in response to insults is still poorly understood. Astrogliosis is a gradatedcontinuum, ranging from diffuse mild or moderate astrogliosis to severe astrogliosis withscar formation. Therefore, the existence of assorted in vitro models seems essential for abetter comprehension of the cellular pathways involved in different scenarios. In thepresent work, we used 2D or 3D in vitro models to analyze astrocyte?s response todifferent stimuli. In a 2D glial scar model, involving meningeal cells, astrocytes forming thescar had increased expression of TLR-2 and TLR-4, two receptors related to innateimmunity. However, we didn?t see increased incorporation of a reporter nanoparticle,which is more avidly up taken by other activated astrocytes. For 3D astrocyte cultures weused a peptide nanofiber scaffold, were astrocytes grew in a more realistic environment,and survived for several weeks with excellent viability and in vivo like morphology. In thiscontext, we were able to produce astrogliosis in response to certain DAMPs, or toleukocytes, but unable to obtain a glial scar. These results show different astrocyticresponses, according to context, and indicate that the 3D model is a more realistic versatileapproach for the study of astrogliosis dynamic responses. PICT2012-1424, CONICET,UBACYT