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 amyloidogenic fragments of amyloid β 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 microglial activation in Aβ1-42- and PrP106-126-stimulated BV2 microglia. results showed that Aβ1-42 and PrP106-126 induced the classical activation of BV2 microglia, decreased the expression level of alternative expression markers, and had no effect on the expression of acquired deactivation markers. Cytochalasin D treatment significantly reduced Aβ1-42- and PrP106-126-induced up-regulation of proinflammatory factors, but did not change the expression profile of the markers of alternative activation or acquired deactivation in BV2 cells which were exposed to Aβ1-42 and PrP106-126. Our results suggested that microglia interact with amyloidogenic peptides in the extracellular milieu-stimulated microglial classical activation and reduce its alternative activation, and that the uptake of amyloidogenic peptides from the extracellular milieu amplifies the classical microglial activation.
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Fushan
F
Shi
Lifeng
L
Yang
Jihong
J
Wang
Mohammed
M
Kouadir
Yang
Y
Yang
Yongyao
Y
Fu
Xiangmei
X
Zhou
Xiaomin
X
Yin
Deming
D
Zhao
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D017628:Microglia / Q000473:pathology*; D010587:Phagocytosis; D016133:Polymerase Chain Reaction; D011328:Prions / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D017931:DNA Primers; D011328:Prions
Alzheimer's disease; microglial activation; prion disease