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Differential Effects of Chronic and Chronic-Intermittent Ethanol Treatment and Its Withdrawal on the Expression of miRNAs.

van Steenwyk G, Janeczek P, Lewohl JM - Brain Sci (2013)

Bottom Line: These expression changes likely underlie the cellular adaptations to long term alcohol misuse.Chronic and chronic-intermittent exposure to ethanol, and its removal, resulted in specific changes in miRNA expression in each cell line suggesting that different expression patterns can be elicited with different exposure paradigms and that the mechanism of ethanol's effects is dependent on cell type.Specifically, chronic exposure to ethanol for five days followed by a five day withdrawal period resulted in up-regulation of several miRNAs in each of these cell lines similar to expression changes identified in post mortem human brain.

View Article: PubMed Central - PubMed

Affiliation: Griffith Health Institute, School of Medical Sciences, Griffith University, Gold Coast Campus, Southport QLD 4215, Australia. gretchencvs16@gmail.com.

ABSTRACT
Chronic and excessive alcohol misuse results in changes in the expression of selected miRNAs and their mRNA targets in specific regions of the human brain. These expression changes likely underlie the cellular adaptations to long term alcohol misuse. In order to delineate the mechanism by which these expression changes occur, we have measured the expression of six miRNAs including miR-7, miR-153, miR-152, miR-15B, miR-203 and miR-144 in HEK293T, SH SY5Y and 1321 N1 cells following exposure to ethanol. These miRNAs are predicted to target key genes involved in the pathophysiology of alcoholism. Chronic and chronic-intermittent exposure to ethanol, and its removal, resulted in specific changes in miRNA expression in each cell line suggesting that different expression patterns can be elicited with different exposure paradigms and that the mechanism of ethanol's effects is dependent on cell type. Specifically, chronic exposure to ethanol for five days followed by a five day withdrawal period resulted in up-regulation of several miRNAs in each of these cell lines similar to expression changes identified in post mortem human brain. Thus, this model can be used to elucidate the role of miRNAs in regulating gene expression changes that occur in response to ethanol exposure.

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Related in: MedlinePlus

The pattern of expression of miRNAs following ethanol treatment. (A) miR-7; (B) miR-152; (C) miR-153 and (D) miR-15B. Data is plotted as mean ± SEM.
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brainsci-03-00744-f001: The pattern of expression of miRNAs following ethanol treatment. (A) miR-7; (B) miR-152; (C) miR-153 and (D) miR-15B. Data is plotted as mean ± SEM.

Mentions: Four of the six miRNAs were expressed by all three cell lines under investigation. Each of these miRNAs shows a distinct pattern of expression following ethanol exposure and this pattern is dependent on the ethanol exposure paradigm used. Furthermore, the expression pattern of these four miRNAs was also significantly different between the three cell lines studied (MANOVA, Cell Line × Treatment Group, miR-7, F2,8 = 9.92 P < 0.0001; miR-153, F2,8 = 15.35 P < 0.0001; miR-152, F2,8 = 10.62 P < 0.0001; miR-15B, F2,8 = 14.58 P < 0.0001). The overall profile of expression across the different treatment groups is shown in Figure 1. The most significant differences in the effect of ethanol exposure on miRNA expression in each cell line is apparent following the chronic ethanol plus withdrawal (CEW) treatment paradigm.


Differential Effects of Chronic and Chronic-Intermittent Ethanol Treatment and Its Withdrawal on the Expression of miRNAs.

van Steenwyk G, Janeczek P, Lewohl JM - Brain Sci (2013)

The pattern of expression of miRNAs following ethanol treatment. (A) miR-7; (B) miR-152; (C) miR-153 and (D) miR-15B. Data is plotted as mean ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061861&req=5

brainsci-03-00744-f001: The pattern of expression of miRNAs following ethanol treatment. (A) miR-7; (B) miR-152; (C) miR-153 and (D) miR-15B. Data is plotted as mean ± SEM.
Mentions: Four of the six miRNAs were expressed by all three cell lines under investigation. Each of these miRNAs shows a distinct pattern of expression following ethanol exposure and this pattern is dependent on the ethanol exposure paradigm used. Furthermore, the expression pattern of these four miRNAs was also significantly different between the three cell lines studied (MANOVA, Cell Line × Treatment Group, miR-7, F2,8 = 9.92 P < 0.0001; miR-153, F2,8 = 15.35 P < 0.0001; miR-152, F2,8 = 10.62 P < 0.0001; miR-15B, F2,8 = 14.58 P < 0.0001). The overall profile of expression across the different treatment groups is shown in Figure 1. The most significant differences in the effect of ethanol exposure on miRNA expression in each cell line is apparent following the chronic ethanol plus withdrawal (CEW) treatment paradigm.

Bottom Line: These expression changes likely underlie the cellular adaptations to long term alcohol misuse.Chronic and chronic-intermittent exposure to ethanol, and its removal, resulted in specific changes in miRNA expression in each cell line suggesting that different expression patterns can be elicited with different exposure paradigms and that the mechanism of ethanol's effects is dependent on cell type.Specifically, chronic exposure to ethanol for five days followed by a five day withdrawal period resulted in up-regulation of several miRNAs in each of these cell lines similar to expression changes identified in post mortem human brain.

View Article: PubMed Central - PubMed

Affiliation: Griffith Health Institute, School of Medical Sciences, Griffith University, Gold Coast Campus, Southport QLD 4215, Australia. gretchencvs16@gmail.com.

ABSTRACT
Chronic and excessive alcohol misuse results in changes in the expression of selected miRNAs and their mRNA targets in specific regions of the human brain. These expression changes likely underlie the cellular adaptations to long term alcohol misuse. In order to delineate the mechanism by which these expression changes occur, we have measured the expression of six miRNAs including miR-7, miR-153, miR-152, miR-15B, miR-203 and miR-144 in HEK293T, SH SY5Y and 1321 N1 cells following exposure to ethanol. These miRNAs are predicted to target key genes involved in the pathophysiology of alcoholism. Chronic and chronic-intermittent exposure to ethanol, and its removal, resulted in specific changes in miRNA expression in each cell line suggesting that different expression patterns can be elicited with different exposure paradigms and that the mechanism of ethanol's effects is dependent on cell type. Specifically, chronic exposure to ethanol for five days followed by a five day withdrawal period resulted in up-regulation of several miRNAs in each of these cell lines similar to expression changes identified in post mortem human brain. Thus, this model can be used to elucidate the role of miRNAs in regulating gene expression changes that occur in response to ethanol exposure.

No MeSH data available.


Related in: MedlinePlus