UMMS Affiliation

Brudnick Neuropsychiatric Research Institute, Department of Neurobiology; Graduate School of Biomedical Sciences, MD/PhD Program; Program in Bioinformatics and Integrative Biology; Graduate School of Biomedical Sciences, Neuroscience Program; Tapper Lab; Gardner Lab

Publication Date

2020-01-21

Document Type

Article

Disciplines

Computational Biology | Genomics | Molecular and Cellular Neuroscience | Nucleic Acids, Nucleotides, and Nucleosides | Substance Abuse and Addiction | Therapeutics

Abstract

Tobacco use is the leading preventable cause of mortality in the world. The limited number of smoking cessation aids currently available are minimally effective, highlighting the need for novel therapeutic interventions. We describe a genome-wide approach to identify potential candidates for such interventions. Next-generation sequencing was performed using RNA isolated from the habenulo-interpeduncular circuit of male mice withdrawn from chronic nicotine treatment. This circuit plays a central role in the nicotine withdrawal response. Differentially expressed miRNAs and mRNAs were validated using RT-qPCR. Many of the differentially expressed mRNAs are predicted targets of reciprocally expressed miRNAs. We illustrate the utility of the dataset by demonstrating that knockdown in the interpeduncular nucleus of a differentially expressed mRNA, that encoding profilin 2, is sufficient to induce anxiety-related behavior. Importantly, profilin 2 knockdown in the ventral tegmental area did not affect anxiety behavior. Our data reveal wide-spread changes in gene expression within the habenulo-interpeduncular circuit during nicotine withdrawal. This dataset should prove to be a valuable resource leading to the identification of substrates for the design of innovative smoking cessation aids.

Keywords

Addiction, Molecular neuroscience

Rights and Permissions

© The Author(s) 2020. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41598-020-57907-w

Source

Sci Rep. 2020 Jan 21;10(1):813. doi: 10.1038/s41598-020-57907-w. Link to article on publisher's site

Journal/Book/Conference Title

Scientific reports

Related Resources

Link to Article in PubMed

PubMed ID

31965003

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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