Micro-RNA abundance and stability in human brain: Specific alterations in Alzheimer's disease temporal lobe neocortex

Sethi, Prerna; Lukiw, Walter J.

doi:10.1016/j.neulet.2009.04.052

Cited by 369 publications

(388 citation statements)

References 30 publications

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“…Key to our approach was the generation of a miR-9 sensor transgenic mouse that provided a detailed expression map of miR-9 activity in the brain. Although this approach does not take into account the absolute expression level or the stability of the miRNA, 23 the use of sensor mice has several advantages over LNA fluorescent ISH, which is the most commonly used method to analyse the expression pattern of individual miRNA in the brain. In particular, the use of a GFP reporter is suitable for colabelling with other markers, here highlighted by the identification of Iba1-expressing microglia as miR-9 negative.…”

Section: Discussionmentioning

confidence: 99%

Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9

et al. 2013

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Functional studies of resident microglia require molecular tools for their genetic manipulation. Here we show that microRNA-9-regulated lentiviral vectors can be used for the targeted genetic modification of resident microglia in the rodent brain. Using transgenic reporter mice, we demonstrate that murine microglia lack microRNA-9 activity, whereas most other cells in the brain express microRNA-9. Injection of microRNA-9-regulated vectors into the adult rat brain induces transgene expression specifically in cells with morphological features typical of ramified microglia. The majority of transgene-expressing cells colabels with the microglia marker Iba1. We use this approach to visualize and isolate activated resident microglia without affecting circulating and infiltrating monocytes or macrophages in an excitotoxic lesion model in rat striatum. The microRNA-9-regulated vectors described here are a straightforward and powerful tool that facilitates functional studies of resident microglia.

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Section: Discussionmentioning

confidence: 99%

Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9

et al. 2013

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“…3 show the sequences of synthetic oligonucleotides used in these studies. DNA sequence characteristics and stabilities for 5 S RNA, miRNA-132, miRNA146a, AM-146a, and AM-146ac have been previously described in detail (29,39) . Figs.…”

Section: Mirna-146a and Irak-2 Signaling In Ad Brainmentioning

confidence: 99%

Differential Regulation of Interleukin-1 Receptor-associated Kinase-1 (IRAK-1) and IRAK-2 by MicroRNA-146a and NF-κB in Stressed Human Astroglial Cells and in Alzheimer Disease

Cui

Zhao

et al. 2010

Journal of Biological Chemistry

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The innate immune response and inflammatory signaling play determinant roles in brain homeostasis, neuroprotection, and repair; however, altered or excessive signaling in these injury defense systems contributes to the irreversible degeneration of brain cells, as typified in the common, age-related neurodegenerative disorder Alzheimer disease (AD). Abundant DNA array, Northern, RT-PCR, and Western gene expression analysis of AD brains have repeatedly shown a significant disruption in the homeostatic expression of essential brain genes and a progressive up-regulation of inflammatory gene expression, driven in part by overactivation of transcription factor NF-B. This supports both the development and progression of neurodegenerative disease processes (9 -16). Indeed the TLR/IL-1R-IRAK-NF-B signaling axis is substantially over-stimulated in AD brain (6, 9 -12). Components of this innate immunity and inflammatory pathway are known to play a central role in driving neuropathology, in part via overexpression of interleukin-1 ␤ (IL-1␤) and upregulating the generation of the 42-amino acid amyloid ␤ 42 (A␤42) peptide. These in turn induce transcription from the * This work was supported, in whole or in part, by National Institutes of Health Grant AG18031 (NIA; to W. J. L.

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“…Tracking the abundance and decay kinetics of specific miRNAs by miRNA array and Northern blot analyses of human neural cells in primary culture and in short post-mortem interval human brain tissues, Sethi and Lukiw (2009) noted a limited stability and relatively short half-life (~1-3.5 h) for specific brain-enriched miRNAs. In short post-mortem interval AD-affected temporal lobe neocortex, miRNA-9, miRNA-125b and miRNA-146a were found to be significantly upregulated, an effect that was not seen in several related neurological disorders (Sethi and Lukiw, 2009), leading the authors to propose that, unless specifically stabilized, certain brain-enriched miRNAs represent a rapidly executed signaling system employing highly transient effectors of CNS gene expression.…”

Section: Micrornas and Alzheimer's Diseasementioning

confidence: 99%

“…In short post-mortem interval AD-affected temporal lobe neocortex, miRNA-9, miRNA-125b and miRNA-146a were found to be significantly upregulated, an effect that was not seen in several related neurological disorders (Sethi and Lukiw, 2009), leading the authors to propose that, unless specifically stabilized, certain brain-enriched miRNAs represent a rapidly executed signaling system employing highly transient effectors of CNS gene expression.…”

Section: Micrornas and Alzheimer's Diseasementioning

confidence: 99%

“…Even when considering and taking into account the relatively short half-lives of some miRNAs (~1 to 3.5 h), short postmortem interval human brain tissues from AD patients exhibited a significant up-regulation of miRNA-146a that was not seen in the same brain regions affected with amyotrophic lateral sclerosis (ALS), schizophrenia or Parkinson's disease (Sethi and Lukiw, 2009), whose pathogenesis is closely related to AD and prion disease in that it involves misfolding and accumulation of fibrillar aggregates of proteins (Tau).…”

Section: Alzheimer's and Prion Diseases Share A Microrna Commonalitymentioning

confidence: 99%

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MicroRNAs as a molecular basis for mental retardation, Alzheimer's and prion diseases

Provost¹

2010

Brain Research

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MicroRNAs (miRNAs) are small, ~21-to 23-nucleotide (nt) non-coding RNA species that act as key regulators of gene expression along a central and well-defined cellular process known as RNA silencing, and involving the recognition and translational control of specific messenger RNA (mRNAs). Generated through the well-orchestrated and sequential processing of miRNA precursor molecules, mature miRNAs are subsequently incorporated into miRNA-containing ribonucleoprotein effector complexes to regulate mRNA translation through the recognition of specific binding sites of imperfect complementarity located mainly in the 3′ untranslated region. Predicted to regulate up to 90% of the genes in humans, miRNAs may thus control cellular processes in all cells and tissues of the human body. Likely to play a central role in health and disease, a dysfunctional miRNA-based regulation of gene expression may represent the main etiologic factor underlying diseases affecting major organs, such as the brain. In this review article, the molecular mechanisms underlying the role and function of miRNAs in the regulation of genes involved in neurological and neurodegenerative diseases will be discussed, with a focus on the fragile X syndrome, Alzheimer's disease (AD) and prion disease.

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Micro-RNA abundance and stability in human brain: Specific alterations in Alzheimer's disease temporal lobe neocortex

Cited by 369 publications

References 30 publications

Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9

Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9

Differential Regulation of Interleukin-1 Receptor-associated Kinase-1 (IRAK-1) and IRAK-2 by MicroRNA-146a and NF-κB in Stressed Human Astroglial Cells and in Alzheimer Disease

MicroRNAs as a molecular basis for mental retardation, Alzheimer's and prion diseases

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