National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
J Neurochem. 2012 Dec;123(5):790-9. doi: 10.1111/jnc.12006. Epub 2012 Oct 25.
Cocaine dependence involves in the brain's reward circuit as well as nucleus accumbens (NAc), a key region of the mesolimbic dopamine pathway. Many studies have documented altered expression of genes and identified transcription factor networks and epigenetic processes that are fundamental to cocaine addiction. However, all these investigations have focused on mRNA of encoding genes, which may not always reflect the involvement of long non-coding RNAs (lncRNAs), which has been implied in a broad range of biological processes and complex diseases including brain development and neuropathological process. To explore the potential involvement of lncRNAs in drug addiction, which is viewed as a form of aberrant neuroplasticity, we used a custom-designed microarray to examine the expression profiles of mRNAs and lncRNAs in brain NAc of cocaine-conditioned mice and identified 764 mRNAs, and 603 lncRNAs were differentially expressed. Candidate lncRNAs were identified for further genomic context characterization as sense-overlap, antisense-overlap, intergenic, bidirection, and ultra-conserved region encoding lncRNAs. We found that 410 candidate lncRNAs which have been reported to act in cis or trans to their targeted loci, providing 48 pair mRNA-lncRNAs. These results suggest that the modification of mRNAs expression by cocaine may be associated with the actions of lncRNAs. Taken together, our results show that cocaine can cause the genome-wide alterations of lncRNAs expressed in NAc, and some of these modified RNA transcripts may to play a role in cocaine-induced neural plasticity and addiction.
可卡因依赖涉及大脑的奖励回路和伏隔核（NAc），这是中脑边缘多巴胺通路的关键区域。许多研究记录了基因表达的改变，并确定了转录因子网络和表观遗传过程，这些对于可卡因成瘾至关重要。然而，所有这些研究都集中在编码基因的 mRNA 上，这可能并不总是反映长非编码 RNA（lncRNA）的参与，lncRNA 已被暗示参与广泛的生物过程和复杂疾病，包括大脑发育和神经病理学过程。为了探索 lncRNA 参与可卡因成瘾的潜在可能性，可卡因成瘾被视为一种异常神经可塑性的形式，我们使用定制设计的微阵列检查了可卡因条件下小鼠脑 NAc 中的 mRNA 和 lncRNA 的表达谱，鉴定出 764 个 mRNA 和 603 个 lncRNA 表达差异。选择候选 lncRNA 进行进一步的基因组上下文特征鉴定，包括 sense-overlap、antisense-overlap、intergenic、bidirection 和编码 lncRNA 的 ultra-conserved region。我们发现 410 个候选 lncRNA 已经被报道在顺式或反式作用于其靶向基因座，提供了 48 对 mRNA-lncRNA。这些结果表明，可卡因引起的 mRNA 表达的修饰可能与 lncRNA 的作用有关。总之，我们的结果表明，可卡因可以导致 NAc 中表达的 lncRNA 的全基因组改变，其中一些修饰的 RNA 转录本可能在可卡因诱导的神经可塑性和成瘾中发挥作用。
