Silencing synaptic MicroRNA‐411 reduces voluntary alcohol consumption in mice
Year: 2018
Type: article
Abstract: Chronic alcohol consumption alters the levels of microRNAs and mRNAs in the brain, but the specific microRNAs and processes that target mRNAs to affect cellular function and behavior are not known. We examined the in vivo manipulation of previously identified alcohol-responsive microRNAs as potential targets to reduce alcohol consumption. Silencing of miR-411 by infusing antagomiR-411 into the prefrontal cortex of female C57BL/6J mice reduced alcohol consumption and preference, without altering total fluid consumption, saccharin consumption, or anxiety-related behaviors. AntagomiR-411 reduced alcohol consumption when given to mice exposed to a chronic alcohol drinking paradigm but did not affect the acquisition of consumption in mice without a history of alcohol exposure, suggesting that antagomiR-411 has a neuroadaptive, alcohol-dependent effect. AntagomiR-411 decreased the levels of miR-411, as well as the association of immunoprecipitated miR-411 with Argonaute2; and, it increased levels of Faah and Ppard mRNAs. Moreover, antagomiR-411 increased the neuronal expression of glutamate receptor AMPA-2 protein, a known alcohol target and a predicted target of miR-411. These results suggest that alcohol and miR-411 function in a homeostatic manner to regulate synaptic mRNA and protein, thus reversing alcohol-related neuroadaptations and reducing chronic alcohol consumption.
Source: Addiction Biology
DOI: 10.1111/adb.12625
Institutions: The University of Texas at Austin, Texas A&M University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Awards: G1795210428, Novel molecular and cellular approaches for alcoholism medication development, Synaptic mRNA and microRNA: Regulation by chronic alcohol consumption, G4962074158, G5327005991, G7603946663, G8338216601, G9000232467, 7/11 Biochemical and Genetic Determinants of Alcohol Consumption, Gene Expression in the Human Alcoholic Brain, 2/11 Spatially Resolved, Single Cell, Neuroimmune Transcriptomes in Alcohol Dependence
OpenAlex ID: W2799306774