PrP^106-126 And Aβ_1-42 Peptides Induce BV-2Microglia Chemotaxis And Proliferation

Transmissible spongiform encephalopathies (TSEs) and Alzheimer’s disease (AD) belong to a growing family of neurodegenerative disorders that is characterized by the generation of toxic protein aggregates in affected brains (PrPSc and Aβ in TSEs and AD, respectively). A close examination of the molecular events associated with TSE and AD reveals that the two share a variety of neuropathological characteristics. At present, clinical and experimental evidence indicates the coexistence of PrP and Aβ amyloid deposits in affected brain tissues. Based on these pathological and mechanistic similarities, relationship between TSEs and AD should be further investigated. In this study, we examined the activation of BV-2microglial chemotaxis and proliferation as well as BV-2cell secretion of MCP-1and TGF-β1after treatment with aggregated forms of PrP106-126and Aβ1-42(separately and together) in vitro in an attempt to understand how protein aggregates can modulate microglial processes in TSEs and AD.1. Comperison between the PrP106-126and Aβ1-42peptides in inducing BV-2Microglia Chemotaxis and ProliferationTo better understand how protein aggregates can modulate microglial processes in these diseases, we treated BV-2microglia with PrP106-126or Aβ1-42peptides individually at five concentrations (5,10,25,50,100μM) for12hr. BV-2microglia chemotaxis index (CI), proliferation index (PI) and MCP-1, TGF-β1, Fractalkine secretion were measured and compared between treatments. The results demonstrated that prp106-126and Aβ1-42peptides induce increases in all four parameters. However, the measured indices plateaued in BV-2cells treated>50μM prP106-126or>10μM Aβ1-42, with the exception of TGF-β1secretion, which continued to increase gradually. The results of this study indicate that Aβ1-42peptides may up-regulate higher microglial chemotaxis and proliferation than prP106-126peptides and BV-2didn’t express Fractalkine.2. PrP106-126and Aβ1-42Peptides induce simultaneously BV-2Microglia Chemotaxis and ProliferationWe treated BV-2microglia with prP106-126or Aβ1-42peptides individually at three different concentrations (25-100μM prP106-12and2.5-10μM Aβ1-42) or with a mixture of PrP106"126and Aβ1-42peptides at specified concentrations for6-24hr. BV-2microglia chemotaxis, proliferation, and MCP-1and TGF-β1secretion were measured and compared between treatments. The results demonstrate that PrP106-126and Aβ1-42peptides induce increases in all four parameters from6-12hr. However, the measured indices plateaued beyond12hr in BV-2cells treated>50μM prP106-126or>5μM Aβ1-42, with the exception of TGF-β1secretion, which continued to increase gradually. Overall, the results of this study indicate that these two peptides have not obviously synergistic or antagonistic effects in inducing microglial chemotaxis and proliferation simultaneously at the protein level.