<i>Gnas</i> Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in Rats
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) res...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/13/3/553 |
| _version_ | 1797471392925483008 |
|---|---|
| author | Peng Liu Jialong Liang Fengze Jiang Wanshi Cai Fang Shen Jing Liang Jianjun Zhang Zhongsheng Sun Nan Sui |
| author_facet | Peng Liu Jialong Liang Fengze Jiang Wanshi Cai Fang Shen Jing Liang Jianjun Zhang Zhongsheng Sun Nan Sui |
| author_sort | Peng Liu |
| collection | DOAJ |
| description | 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 <i>Dnmt3a</i> and <i>Dnmt3b</i>, rather than <i>Dnmt1</i>, 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 (<i>Gnas</i>, <i>Sox10</i>, and <i>Pik3r1</i>) involved in memory modulation. Furthermore, <i>Gnas</i> promoter hypermethylation was confirmed to be inversely correlated with the downregulation of <i>Gnas</i> 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 <i>Gnas</i> in the BLA is necessary for the reconsolidation of morphine reward memories. |
| first_indexed | 2024-03-09T19:47:50Z |
| format | Article |
| id | doaj.art-f78305bdb400436dbf3a84411972bfae |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T19:47:50Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-f78305bdb400436dbf3a84411972bfae2023-11-24T01:20:02ZengMDPI AGGenes2073-44252022-03-0113355310.3390/genes13030553<i>Gnas</i> Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in RatsPeng Liu0Jialong Liang1Fengze Jiang2Wanshi Cai3Fang Shen4Jing Liang5Jianjun Zhang6Zhongsheng Sun7Nan Sui8CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, ChinaBeijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, ChinaBeijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, ChinaCAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, ChinaCAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, ChinaBeijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, ChinaImpairing 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 <i>Dnmt3a</i> and <i>Dnmt3b</i>, rather than <i>Dnmt1</i>, 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 (<i>Gnas</i>, <i>Sox10</i>, and <i>Pik3r1</i>) involved in memory modulation. Furthermore, <i>Gnas</i> promoter hypermethylation was confirmed to be inversely correlated with the downregulation of <i>Gnas</i> 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 <i>Gnas</i> in the BLA is necessary for the reconsolidation of morphine reward memories.https://www.mdpi.com/2073-4425/13/3/553DNA methylationDNA methyltransferasesmorphinebasolateral amygdalareconsolidationmemory |
| spellingShingle | Peng Liu Jialong Liang Fengze Jiang Wanshi Cai Fang Shen Jing Liang Jianjun Zhang Zhongsheng Sun Nan Sui <i>Gnas</i> Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in Rats Genes DNA methylation DNA methyltransferases morphine basolateral amygdala reconsolidation memory |
| title | <i>Gnas</i> Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in Rats |
| title_full | <i>Gnas</i> Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in Rats |
| title_fullStr | <i>Gnas</i> Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in Rats |
| title_full_unstemmed | <i>Gnas</i> Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in Rats |
| title_short | <i>Gnas</i> Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in Rats |
| title_sort | i gnas i promoter hypermethylation in the basolateral amygdala regulates reconsolidation of morphine reward memory in rats |
| topic | DNA methylation DNA methyltransferases morphine basolateral amygdala reconsolidation memory |
| url | https://www.mdpi.com/2073-4425/13/3/553 |
| work_keys_str_mv | AT pengliu ignasipromoterhypermethylationinthebasolateralamygdalaregulatesreconsolidationofmorphinerewardmemoryinrats AT jialongliang ignasipromoterhypermethylationinthebasolateralamygdalaregulatesreconsolidationofmorphinerewardmemoryinrats AT fengzejiang ignasipromoterhypermethylationinthebasolateralamygdalaregulatesreconsolidationofmorphinerewardmemoryinrats AT wanshicai ignasipromoterhypermethylationinthebasolateralamygdalaregulatesreconsolidationofmorphinerewardmemoryinrats AT fangshen ignasipromoterhypermethylationinthebasolateralamygdalaregulatesreconsolidationofmorphinerewardmemoryinrats AT jingliang ignasipromoterhypermethylationinthebasolateralamygdalaregulatesreconsolidationofmorphinerewardmemoryinrats AT jianjunzhang ignasipromoterhypermethylationinthebasolateralamygdalaregulatesreconsolidationofmorphinerewardmemoryinrats AT zhongshengsun ignasipromoterhypermethylationinthebasolateralamygdalaregulatesreconsolidationofmorphinerewardmemoryinrats AT nansui ignasipromoterhypermethylationinthebasolateralamygdalaregulatesreconsolidationofmorphinerewardmemoryinrats |