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Potential Ago2/miR-3068-5p Cascades in the Nucleus Accumbens Contribute to Methamphetamine-Induced Locomotor Sensitization of Mice

Dysregulation of microRNA (miRNA) biogenesis is involved in drug addiction. Argonaute2 (Ago2), a specific splicing protein involved in the generation of miRNA, was found to be dysregulated in the nucleus accumbens (NAc) of methamphetamine (METH)-sensitized mice in our previous study. Here, we determ...

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Autores principales: Liu, Dan, Liang, Min, Zhu, Li, Zhou, Ting-ting, Wang, Yu, Wang, Rui, Wu, Fei-fei, Goh, Eyleen L. K., Chen, Teng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414410/
https://www.ncbi.nlm.nih.gov/pubmed/34483916
http://dx.doi.org/10.3389/fphar.2021.708034
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author Liu, Dan
Liang, Min
Zhu, Li
Zhou, Ting-ting
Wang, Yu
Wang, Rui
Wu, Fei-fei
Goh, Eyleen L. K.
Chen, Teng
author_facet Liu, Dan
Liang, Min
Zhu, Li
Zhou, Ting-ting
Wang, Yu
Wang, Rui
Wu, Fei-fei
Goh, Eyleen L. K.
Chen, Teng
author_sort Liu, Dan
collection PubMed
description Dysregulation of microRNA (miRNA) biogenesis is involved in drug addiction. Argonaute2 (Ago2), a specific splicing protein involved in the generation of miRNA, was found to be dysregulated in the nucleus accumbens (NAc) of methamphetamine (METH)-sensitized mice in our previous study. Here, we determined whether Ago2 in the NAc regulates METH sensitization in mice and identified Ago2-dependent miRNAs involved in this process. We found a gradual reduction in Ago2 expression in the NAc following repeated METH use. METH-induced hyperlocomotor activity in mice was strengthened by knocking down NAc neuronal levels of Ago2 but reduced by overexpressing Ago2 in NAc neurons. Surprisingly, miR-3068-5p was upregulated following overexpression of Ago2 and downregulated by silencing Ago2 in the NAc. Knocking down miR-3068-5p, serving as an Ago2-dependent miRNA, strengthened the METH sensitization responses in mice. These findings demonstrated that dysregulated Ago2 in neurons in the NAc is capable of regulating METH sensitization and suggested a potential role of Ago2-dependent miR-3068-5p in METH sensitization.
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spelling pubmed-84144102021-09-04 Potential Ago2/miR-3068-5p Cascades in the Nucleus Accumbens Contribute to Methamphetamine-Induced Locomotor Sensitization of Mice Liu, Dan Liang, Min Zhu, Li Zhou, Ting-ting Wang, Yu Wang, Rui Wu, Fei-fei Goh, Eyleen L. K. Chen, Teng Front Pharmacol Pharmacology Dysregulation of microRNA (miRNA) biogenesis is involved in drug addiction. Argonaute2 (Ago2), a specific splicing protein involved in the generation of miRNA, was found to be dysregulated in the nucleus accumbens (NAc) of methamphetamine (METH)-sensitized mice in our previous study. Here, we determined whether Ago2 in the NAc regulates METH sensitization in mice and identified Ago2-dependent miRNAs involved in this process. We found a gradual reduction in Ago2 expression in the NAc following repeated METH use. METH-induced hyperlocomotor activity in mice was strengthened by knocking down NAc neuronal levels of Ago2 but reduced by overexpressing Ago2 in NAc neurons. Surprisingly, miR-3068-5p was upregulated following overexpression of Ago2 and downregulated by silencing Ago2 in the NAc. Knocking down miR-3068-5p, serving as an Ago2-dependent miRNA, strengthened the METH sensitization responses in mice. These findings demonstrated that dysregulated Ago2 in neurons in the NAc is capable of regulating METH sensitization and suggested a potential role of Ago2-dependent miR-3068-5p in METH sensitization. Frontiers Media S.A. 2021-08-13 /pmc/articles/PMC8414410/ /pubmed/34483916 http://dx.doi.org/10.3389/fphar.2021.708034 Text en Copyright © 2021 Liu, Liang, Zhu, Zhou, Wang, Wang, Wu, Goh and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Liu, Dan
Liang, Min
Zhu, Li
Zhou, Ting-ting
Wang, Yu
Wang, Rui
Wu, Fei-fei
Goh, Eyleen L. K.
Chen, Teng
Potential Ago2/miR-3068-5p Cascades in the Nucleus Accumbens Contribute to Methamphetamine-Induced Locomotor Sensitization of Mice
title Potential Ago2/miR-3068-5p Cascades in the Nucleus Accumbens Contribute to Methamphetamine-Induced Locomotor Sensitization of Mice
title_full Potential Ago2/miR-3068-5p Cascades in the Nucleus Accumbens Contribute to Methamphetamine-Induced Locomotor Sensitization of Mice
title_fullStr Potential Ago2/miR-3068-5p Cascades in the Nucleus Accumbens Contribute to Methamphetamine-Induced Locomotor Sensitization of Mice
title_full_unstemmed Potential Ago2/miR-3068-5p Cascades in the Nucleus Accumbens Contribute to Methamphetamine-Induced Locomotor Sensitization of Mice
title_short Potential Ago2/miR-3068-5p Cascades in the Nucleus Accumbens Contribute to Methamphetamine-Induced Locomotor Sensitization of Mice
title_sort potential ago2/mir-3068-5p cascades in the nucleus accumbens contribute to methamphetamine-induced locomotor sensitization of mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414410/
https://www.ncbi.nlm.nih.gov/pubmed/34483916
http://dx.doi.org/10.3389/fphar.2021.708034
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