Gnas Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in Rats

被引:8
作者
Liu, Peng [1 ,2 ]
Liang, Jialong [3 ]
Jiang, Fengze [1 ,2 ]
Cai, Wanshi [3 ]
Shen, Fang [1 ,2 ]
Liang, Jing [1 ,2 ]
Zhang, Jianjun [1 ,2 ]
Sun, Zhongsheng [3 ,4 ]
Sui, Nan [1 ,2 ]
机构
[1] Inst Psychol, CAS Key Lab Mental Hlth, Beijing 100101, Peoples R China
[2] Univ Chinese Acad Sci, Dept Psychol, Beijing 100101, Peoples R China
[3] Chinese Acad Sci, Beijing Inst Life Sci, Beijing 100101, Peoples R China
[4] Wenzhou Med Univ, Inst Genom Med, Wenzhou 325000, Peoples R China
基金
中国国家自然科学基金;
关键词
DNA methylation; DNA methyltransferases; morphine; basolateral amygdala; reconsolidation; memory; INDUCED PLACE PREFERENCE; POST-RETRIEVAL EXTINCTION; DNA METHYLATION; NUCLEUS-ACCUMBENS; PROTEIN-SYNTHESIS; ACTIVATION; RECEPTORS; KINASE; GENE; NMDA;
D O I
10.3390/genes13030553
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Impairing reconsolidation may disrupt drug memories to prevent relapse, meanwhile long-term transcription regulations in the brain regions contribute to the occurrence of emotional memories. The basolateral amygdala (BLA) is involved in the drug-cue association, while the nucleus accumbens (NAc) responds to the drug reward. Here, we assessed whether DNA methyltransferases (Dnmts) in these two brain regions function identically in the reconsolidation of morphine reward memory. We show that Dnmts inhibition in the BLA but not in the NAc after memory retrieval impaired reconsolidation of a morphine reward memory. Moreover, the mRNA levels of Dnmt3a and Dnmt3b, rather than Dnmt1, in the BLA were continuously upregulated after retrieval. We further identified the differentially methylated regions (DMRs) in genes in the BLA after retrieval, and focused on the DMRs located in gene promoter regions. Among them were three genes (Gnas, Sox10, and Pik3r1) involved in memory modulation. Furthermore, Gnas promoter hypermethylation was confirmed to be inversely correlated with the downregulation of Gnas mRNA levels. The findings indicate that the specific transcription regulation mechanism in the BLA and NAc on reconsolidation of opiate-associated memories can be dissociable, and DNA hypermethylation of Gnas in the BLA is necessary for the reconsolidation of morphine reward memories.
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页数:16
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