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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
mRNA changes in nucleus accumbens related to methamphetamine addiction in mice
Li Zhu1,2, Jiaqi Li1,2, Nan Dong1,2
1College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, PR China.
Abstract:
Methamphetamine (METH) is a highly addictive psychostimulant that elicits aberrant changes in the expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the nucleus accumbens of mice, indicating a potential role of METH in post-transcriptional regulations. To decipher the potential consequences of these post-transcriptional regulations in response to METH, we performed strand-specific RNA sequencing (ssRNA-Seq) to identify alterations in mRNA expression and their alternative splicing in the nucleus accumbens of mice following exposure to METH. METH-mediated changes in mRNAs were analyzed and correlated with previously reported changes in non-coding RNAs (miRNAs and lncRNAs) to determine the potential functions of these mRNA changes observed here and how non-coding RNAs are involved. A total of 2171 mRNAs were differentially expressed in response to METH with functions involved in synaptic plasticity, mitochondrial energy metabolism and immune response. 309 and 589 of these mRNAs are potential targets of miRNAs and lncRNAs respectively. In addition, METH treatment decreases mRNA alternative splicing, and there are 818 METH-specific events not observed in saline-treated mice. Our results suggest that METH-mediated addiction could be attributed by changes in miRNAs and lncRNAs and consequently, changes in mRNA alternative splicing and expression. In conclusion, our study reported a methamphetamine-modified nucleus accumbens transcriptome and provided non-coding RNA-mRNA interaction networks possibly involved in METH addiction.
Insights
Methamphetamine (METH) alters gene expression and splicing in the mouse brain, impacting synaptic plasticity and metabolism. These changes, driven by non-coding RNAs, may underlie METH addiction.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- Methamphetamine (METH) is a psychostimulant causing addiction.
- METH alters microRNA (miRNA) and long non-coding RNA (lncRNA) expression in the nucleus accumbens.
- These non-coding RNA changes suggest METH impacts post-transcriptional regulation.
Purpose of the Study:
- To identify mRNA expression and alternative splicing alterations in the mouse nucleus accumbens after METH exposure.
- To correlate METH-induced mRNA changes with known non-coding RNA alterations.
- To elucidate the role of non-coding RNAs in METH's effects on the transcriptome.
Main Methods:
- Strand-specific RNA sequencing (ssRNA-Seq) was used to analyze gene expression and splicing.
- Differential gene expression analysis identified METH-responsive mRNAs.
- Bioinformatic analysis correlated mRNA changes with miRNA and lncRNA targets.
Main Results:
- METH significantly altered the expression of 2171 mRNAs involved in synaptic plasticity, mitochondrial energy metabolism, and immune response.
- 309 and 589 differentially expressed mRNAs were predicted as targets of miRNAs and lncRNAs, respectively.
- METH treatment reduced mRNA alternative splicing, with 818 METH-specific splicing events identified.
Conclusions:
- METH addiction may result from altered miRNA and lncRNA expression, leading to changes in mRNA splicing and expression.
- The study reveals a METH-modified nucleus accumbens transcriptome.
- Identified non-coding RNA-mRNA interaction networks offer insights into METH addiction mechanisms.

