Soluble oligomeric forms of beta-amyloid (Aβ) peptide stimulate Aβ production via astrogliosis in the rat brain

The aim of this study was to investigate the interaction between beta-amyloid (Aβ) peptide and astrogliosis in early stages of Aβ toxicity. In Wistar rats, anaesthetised with equitesine, a single microinjection of Aβ1-42 oligomers was placed into the retrosplenial cortex. Control animals were injected with Aβ42-1 peptide into the corresponding regions of cerebral cortex. Immunocytochemical analysis revealed an intense Aβ immunoreactivity (IR) at the level of Aβ1-42 injection site, increasing from the first 24 h to later (72 h) time point. Control injection showed a light staining surrounding the injection site. In Aβ oligomers-treated animals, Aβ-immunopositive product also accumulates in cortical cells, particularly in frontal and temporal cortices at an early (24 h) time point. Aβ-IR structures-like diffuse aggregates forms were also observed in hippocampus and in several cortical areas, increasing from the first 24 h to later (72 h) time point. In control animals no specific staining was seen neither in cortical cells nor in structures-like diffuse aggregates forms. Injections of Aβ oligomers also induce activation of astrocytes surrounding and infiltrating the injection site. Astrocyte activation is evidenced by morphological changes and upregulation of glial fibrillary acidic protein (GFAP). By GFAP immunoblotting we detected two immunopositive protein bands, at 50 and 48 kDa molecular mass. Confocal analysis also showed that GFAP co-localized with Aβ-IR material in a time-dependent manner. In conclusion, our results indicate that astrocyte activation might have a critical role in the mechanisms of Aβ-induced neurodegeneration, and that should be further studied as possible targets for therapeutic intervention in AD.