Transcriptome profiling of whisker follicles in methamphetamine self-administered rats

Abstract

Methamphetamine (MA) is a highly addictive psychostimulant that disturbs the central nervous system; therefore, diagnosis of MA addiction is important in clinical and forensic toxicology. In this study, a MA self-administration rat model was used to illustrate the gene expression profiling of the rewarding effect caused by MA. RNA-sequencing was performed to examine changes in gene expression in rat whisker follicles collected before self-administration, after MA self-administration, and after withdrawal sessions. We identified six distinct groups of genes, with statistically significant expression patterns. By constructing the functional association network of these genes and performing the subsequent topological analysis, we identified 43 genes, which have the potential to regulate MA reward and addiction. The gene pathways were then analysed using the Reactome and Knowledgebase for Addiction-Related Gene database, and it was found that genes and pathways associated with Alzheimer’s disease and the heparan sulfate biosynthesis were enriched in MA self-administration rats. The findings suggest that changes of the genes identified in rat whisker follicles may be useful indicators of the rewarding effect of MA. Further studies are needed to provide a comprehensive understanding of MA addiction.

Transcriptional Profiling of Whisker Follicles and of the Striatum in Methamphetamine Self-Administered Rats

“…However, in this context, it is noteworthy that Arc is required for postsynaptic trafficking and processing of Appand amyloid β formation, which appear to be relevant to AD pathogenesis [ 31 ]. In whisker follicles, the App gene has been identified as a potential marker gene, which is in agreement with our previous data suggesting that App is an addiction-related gene in the whisker follicle in MA self-administered rats [ 9 ]. Although much remains to be studied, we cannot ignore the possibility that MA-induced genetic changes disturbing homeostatic synaptic plasticity in the brain are somehow reflected in whisker follicles, thereby linking the functions between striatal tissues and whisker follicle tissues.…”

“…After co-examining the gene expression in hair follicles and post-mortem brain tissue samples from patients with autism, they suggested that hair follicles may serve as an alternative apparatus reflecting the state of the central nervous system [ 8 ]. Consistently with this finding, our previous data have revealed that alterations of gene expression patterns in the whisker follicles of MA self-administered rats may serve as useful indicators of MA rewards [ 9 ]. However, to date, large-scale evaluation and comparison of the molecular changes have not been conducted between hair follicles and the striatum.…”

“…To find potential diagnostic genes in this pathological process, the transcriptional changes caused by MA self-administration were investigated in whisker follicles and in the striatum. Previously, we have explored the changes in gene expression in the whisker follicle of MA self-administered rats to identify novel indicators of the MA reward and found that gene expression in the whisker follicle could be used to understand the rewarding effect of MA in the striatum [ 9 ]. Nonetheless, nobody has directly examined the concomitant gene expression during MA self-administration both in the striatum and in whisker follicles of the same rat at the same time points, nor have any researchers placed their results in the context of systems biology.…”

“…After two-way RM ANOVA, Bonferroni multiple comparison tests were used for post-hoc analysis. After the end of the MA self-administration protocol, whisker follicles and the striatum were collected as described elsewhere [ 9 , 39 ]. The collected tissue samples were stored at −80 °C until analysis.…”

Pathologic complete response to chemoembolization improves survival outcomes after curative surgery for hepatocellular carcinoma: predictive factors of response

“…The radiological response evaluation was performed by two board-certified radiologists according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). 25 Target lesions were defined as those with the largest diameter of 1 cm or more and non-target lesions as those with largest diameter of less than 1 cm. 25 To evaluate treatment response, two lesions per organ and five lesions in total were maximally selected.…”