Inhibition of phagocytosis reduced the classical activation of BV2 microglia induced by amyloidogenic fragments of beta-amyloid and prion proteins

The inflammatory responses in Alzheimer＇s disease and prion diseases are dominated by microglia activation. Three different phenotypes of microglial activation, namely classical activation, alternative activation, and acquired deactivation, have been described. In this study, we investigated the effect of amyloido- genic fragments of amyloid 13 and prion proteins （Aβ1_42 and PrP106-126） on various forms of microglial activation. We first examined the effect of Aβ1_42 and PrP106-126 stimulation on the mRNA expression levels of several markers of microglial activation, as well as the effect of cytochalasin D, a phagocytosis inhibitor, on microgllal activation in Aβ1_42- and PrP106-126- stimulated BV2 microglla. Results showed that Aβ1-42 and PrPlo6_126 induced the classical activation of BV2 microglia, decreased the expression level of alternative expression markers, and had no effect on the expression of acquired de- activation markers. Cytochalasin D treatment significantly reduced Aβ1_42- and PrP106-26-induced up-regulation of proinflammatory factors, but did not change the expression profile of the markers of alternative activation or acquired de- activation in BV2 cells which were exposed to Aβ1-42 and PrPlo6_126. Our results suggested that microglia interact with amyloidogenic peptides in the extraceilular milieu-stimulated microglial classical activation and reduce its alternative activa- tion, and that the uptake of amyloidogenic peptides from the extracellular milieu amplifies the classical microglial activation.