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Monday, May 7, 2012

MALAT-1, a non protein-coding RNA is upregulated in the cerebellum, hippocampus and brain stem of human alcoholics

Chronic alcohol intake induces neurochemical adaptative changes in the brain characterised by altered gene expression. A role for non-coding RNAs in alcoholism is beginning to emerge. PCR-differential display using total RNA extracted from brain material of human alcoholics and control cases identified a cDNA fragment corresponding to a section of a known non protein-coding RNA (ncRNA), MALAT-1, (also known as NEAT2).

Comparison of mRNA levels of MALAT-1 was performed by northern and dot blot experiments using different regions of brain from human alcoholics and rats chronically treated with ethanol vapours and following withdrawal.

A massive increase of MALAT-1 transcripts was detected in cerebellum of human alcoholics and increases were also noted in hippocampus and brain stem, while no significant increase of MALAT-1 expression was noted in frontal or motor cortices.

In the rat no significant difference of MALAT-1 ortholog mRNA could be detected in cerebellum. In addition, similarly to humans, no significant increase of MALAT-1 expression was detected in cortex of alcohol-treated rats, however, after 24 h alcohol withdrawal, a significant upregulation of MALAT-1 expression was observed in rat cortex. MALAT-1 is upregulated in specific regions of the human alcoholic brain and following alcohol withdrawal in the rat.

As MALAT-1 regulates RNA processing, this suggests that alcohol-induced upregulation of MALAT-1 represents an important novel mechanism for alcohol actions in the CNS.

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