RESUMO
Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia-touching plaques, neighboring plaques, and far from plaques in an aged Alzheimer's mouse model with late plaque development. In 18-month-old APPNL-F/NL-F knockin mice, with and without the Alzheimer's disease risk mutation Trem2R47H/R47H, we report that expression of 38/55 PIGs have plaque-induced microglial upregulation, with a subset only upregulating in microglia directly contacting plaques. For seven PIGs, including Trem2, this upregulation is prevented in APPNL-F/NL-FTrem2R47H/R47H mice. These TREM2-dependent genes are all involved in phagocytic and degradative processes that we show correspond to a decrease in phagocytic markers and an increase in the density of small plaques in Trem2-mutated mice. Furthermore, despite the R47H mutation preventing increased Trem2 gene expression, TREM2 protein levels and microglial density are still marginally increased on plaques. Hence, both microglial contact with plaques and functioning TREM2 are necessary for microglia to respond appropriately to amyloid pathology.
Assuntos
Doença de Alzheimer , Amiloidose , Animais , Camundongos , Microglia/metabolismo , Doença de Alzheimer/metabolismo , Placa Amiloide/metabolismo , Proteínas Amiloidogênicas/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismoRESUMO
Cells electrical fields have a significant role in cell function. AIM: The current study examined the effects of nanoscale electric fields generated by magneto-electric nanoparticles (MENs) on precancerous liver tissue. METHODS & RESULTS: A total of 30 nm MENs synthesized by sol-gel method were tested in vitro on HepG2 cells and in vivo on liver cell dysplasia in mice, which were exposed to 50 Hz 2 mT for 2 weeks, +/- MENs. MENs with alternating field (AF) reversed liver cells dysplastic features. In vitro cytotoxicity assay showed high lethal dose (LD 50) of 1.4 mg/ml. We also report on the expression of alpha-fetoprotein and cytochrome C. CONCLUSION: MEN-generated nanoscale electric fields have significant biological effects on precancerous liver cells.