Elsevier

Neuroscience Letters

Volume 487, Issue 1, 3 January 2011, Pages 94-98
Neuroscience Letters

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

https://doi.org/10.1016/j.neulet.2010.09.079Get rights and content

Abstract

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.

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Acknowledgments

Thanks are extended to Darlene Guillot and Aileen Pogue for expert technical assistance, and to Drs. C. Bergeron, C. Chen, J. Deck, P.E. Fraser, E. Head, D.R. McLachlan, W. Poon, G. Tejada and T. Saing for Tg-AD mouse and human brain and retinal tissues or extracts. Some of the brain tissues used in this project was provided by the Institute for Memory Impairments and Neurological Disorders and the University of California at Irvine Alzheimer's Disease Research Center (UCI-ADRC); funding for

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