RNA profiling in medial prefrontal cortex of morphine addiction mice
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ABSTRACT: total RNA-sequencing in mPFC from 3 saline control mice and 3 morphine addiction mice after morphine-induced conditioned place preference(CPP)
Project description:The current study aimed at addressing two questions: 1) How the expression of key lncRNAs is altered in the NAc during the morphine-induced addiction? 2) Which is/are the target gene(s) and what is/are the regulatory mechanism(s) of gene(s) in response to the candidate lncRNAs? To answer these two questions, the morphine addiction model was first established by using the conditioned place preference (CPP) paradigm. Then, the aberrant expression of lncRNAs was identified in the NAc tissue by RNA-sequencing.
Project description:The current study aimed at addressing two questions: 1) How the expression of key miRNAs is altered in the NAc during the morphine-induced addiction? 2) Which is/are the target gene(s) and what is/are the regulatory mechanism(s) of gene(s) in response to the candidate miRNAs? To answer these two questions, the morphine addiction model was first established by using the conditioned place preference (CPP) paradigm. Then, the aberrant expression of miRNAs was identified in the NAc tissue by RNA-sequencing.
Project description:The current study aimed at addressing a question: How the expression of key lncRNAs is altered in the NAc during the formation of morphine addiction memory? To answer these two questions, the mice were trained by using the conditioned place preference (CPP) paradigm. Then, the aberrant expression of lncRNAs was identified in the NAc tissue of the mice by RNA-sequencing.
Project description:Lysine demethylase 7A (KDM7A) catalyzes the removal of dimethylation from histone H3 lysine 9 and lysine 27, both of which are associated with transcription repression. Previous study indicated that Kdm7a mRNA in the medial prefrontal cortex (mPFC) increased after drug exposure, yet its role in drug-related behaviors is largely unknown. In a morphine-conditioned place preference (CPP) paradigm, our findings revealed a specific increase of Kdm7a expression in the mPFC seven days after drug withdrawal. Subsequently, our results demonstrated that knockdown of Kdm7a in the mPFC did not affect the acquisition of morphine-induced CPP, but it attenuated memory consolidation. To further explore Kdm7a-mediated transcriptomic changes, we employed Nanopore direct RNA sequencing. Transcriptome profiling unveiled several gene expression alterations impacted by KDM7A, which were enriched in relevant neural function categories. Notably, we identified and validated fascin actin-bundling protein 1 (Fscn1) as a downstream molecular target. Knockdown of Fscn1 had a similar impact on CPP to Kdm7a, along with a corresponding decrease in dendritic spine density in the mPFC. Additionally, ChIP analysis demonstrated that silencing Kdm7a in N2a cells resulted in decreased enrichment of H3K9me2 and H3K27me2 at the Fscn1 promoter region, suggesting that Kdm7a may act as a crucial regulator of transcriptional responses to morphine-related reward memory via Fscn1.
Project description:Drug addiction represents a pathological form of learning and memory with profound implications for individuals and society. The serotonin receptor 5-HT6R, uniquely expressed on primary cilia, is associated with neurological development, cognitive impairments, emotional disorders, and reward memory for cocaine and nicotine. However, its role in morphine-related reward memory remains unclear. This study demonstrated that 5-HT6R expression was downregulated during the early stage of morphine-induced conditioned place preference (CPP) extinction but returned to baseline levels later, with no significant changes observed during CPP establishment or reinstatement. Knocking down 5-HT6R accelerated CPP extinction, while overexpression prolonged the process. Furthermore, primary cilia defects within the mPFC were noted during the early stage of CPP extinction, and the removal of primary cilia expedited this process. Finally, ATR was identified as a novel target molecule of 5-HT6R, and the 5-HT6R-ATR-primary cilia network was found to regulate morphine-induced CPP extinction, offering new insights for opioid addiction therapy.
Project description:We examined the influence of chronic morphine on microRNA expression profile in the mPFC using miRNA microarray technology. We found that 97 miRNAs (59 upregulated and 38 downregulated) were altered more than 2-fold in the mPFC from chronic morphine-treated rats.
Project description:To investigate the candidate molecular mechanisms underlies methamphetamine-associated CPP memory retrieval and reconsolidation, we compared the transcriptional profling changes in the mPFC between mice that underwent retrieval and non-retrieval after methamphetamine-paired CPP training.