Transcriptomic Changes of Astrocytes in the Brain of Rats with Subacute METH Exposure

Abstract

ObjectiveTo study the transcriptomic changes of astrocytes in the brain of rats exposed to methamphetamine （METH） and its possible mechanism in neurotoxicity.MethodsThe rats were intraperitoneally injected with METH （15 mg/kg） every 12 h for 8 times in total to establish the subacute rat model of METH. After the model was successfully established, the striatum was extracted, and astrocytes were separated by the magnetic bead method. Transcriptome sequencing was performed on selected astrocytes, and the differentially expressed genes were analyzed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis.ResultsA total of 876 differentially expressed genes were obtained by transcriptome sequencing, including 321 up-regulated genes and 555 down-regulated genes. GO analysis revealed that differentially expressed genes were mainly concentrated in cell structure, biological process regulation, extracellular matrix and organelle functions. KEGG pathway enrichment analysis showed that steroids biosynthesis, fatty acid biosynthesis, peroxisome proliferators-activated receptor （PPAR）, adenosine 5’-monophosphate-activated protein kinase （AMPK） and other signaling pathways were significantly changed.ConclusionMETH can cause structural changes of astrocytes through multiple targets, among which cellular structure, steroids biosynthesis and fatty acid biosynthesis may play an important role in nerve injury, providing a new idea for forensic identification of METH related death.

Keywords

• forensic toxicology
• transcriptomics
• methamphetamine
• astrocyte
• differentially expressed genes
• signaling pathway