Increased expression of miRNA-146a in Alzheimer's disease transgenic mouse models

A mouse and human brain-enriched micro-RNA-146a (miRNA-146a) is known to be important in modulating the innate immune response and inflammatory signaling in certain immunological and brain cell types. In this study we examined miRNA-146a levels in early-, moderate- and late-stage Alzheimer's disease (AD) neocortex and hippocampus, in several human primary brain and retinal cell lines, and in 5 different transgenic mouse models of AD including Tg2576, TgCRND8, PSAPP, 3xTg-AD and 5xFAD. Inducible expression of miRNA-146a was found to be significantly up-regulated in a primary co-culture of human neuronal–glial (HNG) cells stressed using interleukin1-beta (IL-1β), and this up-regulation was quenched using specific NF-кB inhibitors including curcumin. Expression of miRNA-146a correlated with senile plaque density and synaptic pathology in Tg2576 and in 5xFAD transgenic mouse models used in the study of this common neurodegenerative disorder.

Research highlights▶ Micro-RNA 146a (miRNA-146a) is a mouse and human brain-enriched miRNA implicated in the innate immune response and inflammatory signaling. ▶ miRNA-146a was found to be up-regulated both in Alzheimer disease brain and in several transgenic mouse models of Alzheimer's disease including Tg2576, TgCRND8, PSAPP, 3xTg-AD and 5xFAD. ▶ In IL-1β stressed primary co-cultures of human neuronal and glial (HNG) cells, miRNA-146a up-regulation was quenched using the NF-кB inhibitors curcumin, PDTC or CAY10512, suggesting a novel regulatory interplay between the inducible, pro-inflammatory transcription factor NF-кB and miRNA-146a.