Integrated whole-transcriptome analysis reveals ceRNA network dysregulation underlying methcathinone-induced synaptic
Rukui Zhou1, Chunming Xu2, Zhe Chen2
1School of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, China; School of Forensic Medicine, Shanxi Medical University, Jinzhong, Shanxi, China.
Summary
Methcathinone (MCAT) exposure in rats impairs cognitive function and synaptic structure by disrupting gene expression. This study reveals complex molecular networks underlying MCAT neurotoxicity, offering potential therapeutic targets for psychostimulant-induced cognitive deficits.
Area of Science:
- Neuroscience
- Toxicology
- Molecular Biology
Background:
- Methcathinone (MCAT), a synthetic cathinone, presents significant public health risks due to its addictive potential and neurotoxicity.
- Understanding the molecular mechanisms of MCAT-induced neurotoxicity is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the effects of MCAT on cognitive function and hippocampal synaptic integrity in a rat model.
- To elucidate the molecular pathways, including multi-transcriptomic changes and competing endogenous RNA (ceRNA) networks, involved in MCAT neurotoxicity.
Main Methods:
- Establishment of MCAT-induced neurotoxicity rat models at low, medium, and high doses.
- Assessment of cognitive function using the Morris water maze.
- Examination of hippocampal synaptic morphology via Golgi staining and transmission electron microscopy.
- Whole-transcriptome sequencing (mRNAs, miRNAs, circRNAs, lncRNAs) and bioinformatic analyses, including ceRNA network construction.
- Validation of RNA-seq data using quantitative RT-PCR.
Main Results:
- MCAT exposure led to dose-dependent cognitive deficits and impaired hippocampal synaptic structure.
- Extensive transcriptional alterations were observed, with significant differential expression of mRNAs, miRNAs, circRNAs, and lncRNAs.
- Activity-dependent immediate-early genes were downregulated, indicating disrupted neuronal activity.
- Construction of core ceRNA networks revealed complex post-transcriptional regulatory interactions underlying MCAT neurotoxicity.
Conclusions:
- MCAT induces cognitive deficits and synaptic damage by disrupting activity-dependent gene expression and neurotrophic signaling.
- Complex ceRNA networks play a critical role in mediating MCAT-induced neurotoxicity.
- This study identifies potential molecular targets for therapeutic strategies against psychostimulant-related cognitive dysfunction.
