MicroRNAs and Ethanol Toxicity

Miranda, Rajesh C.

doi:10.1016/b978-0-12-801311-3.00007-x

Cited by 29 publications

(23 citation statements)

References 156 publications

(213 reference statements)

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“…Similarly, expression-profiling studies in postmortem brains of human alcoholics have shown that the transcriptional reprogramming that takes place is brain region-specific and may reflect both pre-existing differences in gene expression and alterations in response to alcohol consumption (Nunez & Mayfield, 2012; Nunez, Truitt, Gorini, Ponomareva, Blednov, et al, 2013). In addition, epigenetic reprogramming primarily mediated by direct methylation of DNA and acetylation, methylation, and phosphorylation of histone proteins, appears to contribute to the altered gene expression observed in alcoholics and animal models of excessive alcohol consumption (Krishnan, Sakharkar, Teppen, Berkel, & Pandey, 2014; Miranda, 2014). The first transcriptome-wide study of alcohol-responsive miRNAs in human alcoholics identified ~35 upregulated human miRNAs in the prefrontal cortex (PFC) (Lewohl et al, 2011).…”

Section: Micrornamentioning

confidence: 99%

Emerging roles for ncRNAs in alcohol use disorders

Mayfield

2017

Alcohol

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Chronic alcohol exposure produces widespread neuroadaptations and alterations in gene expression in human alcoholics and animal models. Technological advances in the past decade have increasingly highlighted the role of non-protein-coding RNAs (ncRNAs) in the regulation of gene expression and function. These recently characterized molecules were discovered to mediate diverse processes in the central nervous system, from normal development and physiology to regulation of disease, including alcoholism and other psychiatric disorders. This review will investigate the recent studies in human alcoholics and rodent models that have profiled different classes of ncRNAs and their dynamic alcohol-dependent regulation in brain.

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Section: Micrornamentioning

confidence: 99%

Emerging roles for ncRNAs in alcohol use disorders

Mayfield

2017

Alcohol

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“…In the CNS, specific miRNAs fluctuate in neurons (Jovicic et al, 2013), astrocytes and oligodendrocytes (Lau et al, 2008) following injury or metabolic stress (Feng & Feng, 2011; Liu & Xu, 2011). More recently, miRNA alterations in particular brain regions have been associated with psychiatric disorders such as depression, schizophrenia (Dwivedi, 2014; Kocerha, Dwivedi, & Brennand, 2015; Smalheiser et al, 2014) or alcoholism (Rajesh C. Miranda, 2014; R. C. Miranda et al, 2010), suggesting pathophysiological involvement of miRNAs.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-21: Expression in oligodendrocytes and correlation with low myelin mRNAs in depression and alcoholism

Miguel-Hidalgo

Hall

Bonner

et al. 2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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MiR-21 is a microRNA implicated in cancer, development, and cardiovascular diseases and expressed in the central nervous system (CNS), especially after injury. However, the cellular expression of miR-21 in the adult CNS has not been clearly established either in mice or human subjects, while its alteration in psychiatric disorders is unknown. MiR-21 expression was characterized in reporter mice expressing β–galactosidase (LacZ) under the endogenous miR-21 promoter (miR-21/LacZ). Brain co-localization of miR-21/LacZ with specific neural markers was examined by double immunofluorescence in reporter mice, while extent of immunostaining for myelin basic protein and PDGFRα was determined in miR-21 knockout and wild-type mice. Levels of miR-21, and mRNAs of selected miR-21 targets, miR-21 regulator STAT3 and myelin-related proteins were measured by qRT-PCR in the white matter (WM) adjacent to the left postmortem orbitofrontal cortex (OFC) of human subjects with major depressive disorder (MDD), alcoholism, comorbid MDD plus alcoholism (MDA) and non-psychiatric control subjects. MiR-21/LacZ was highly expressed in cell bodies of WM and myelinated portions of gray matter (GM). Labeled cell bodies were identified as oligodendrocytes, while miR-21/LacZ was barely detectable in other cell types. MiR-21, as well as the mRNAs of several myelin-related proteins, were reduced in the WM of subjects with MDD and alcoholism. MiR-21 positively correlated with mRNA of myelin-related proteins and astrocytic GFAP. High expression of miR-21 in adult oligodendrocytes and the correlation of miR-21 decrease with mRNA of some myelin proteins, regulator STAT3, and oligodendrocyte-related transcription factors suggest an involvement of miR-21 in WM alterations in depression and alcoholism.

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“…MiRNAs regulate cellular function and maturation state by repressing the translation of networks of protein-coding genes (for review, see (Miranda, 2014)). We previously showed that early developmental exposure to alcohol resulted in alterations in miRNAs (Sathyan et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure

Balaraman

Idrus

Miranda

et al. 2017

Alcohol

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Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol’s developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol’s long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4–9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4–21. On PD 22, subjects were sacrificed, and RNA isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was normalized with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p<0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p<0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by ethanol. These findings have important implications for the mechanisms by which choline may serve as a potential treatment for FASD.

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MicroRNAs and Ethanol Toxicity

Cited by 29 publications

References 156 publications

Emerging roles for ncRNAs in alcohol use disorders

Emerging roles for ncRNAs in alcohol use disorders

MicroRNA-21: Expression in oligodendrocytes and correlation with low myelin mRNAs in depression and alcoholism

Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure

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