Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens.
Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens.
复制标题
成瘾和与奖励相关的基因在产后拟核中显示出改变的表达。
DOI：
10.3389/fnbeh.2014.00388
复制
发表时间：
2014
影响因子：
3
通讯作者：
Gammie SC
中科院分区：
文献类型：
--
作者：
Zhao C;Eisinger BE;Driessen TM;Gammie SC
为人母涉及到自然回报的转换，从而使后代变得非常有回报。伏隔核(NAC)是自然奖赏和成瘾的关键中枢神经系统区域，但到目前为止还没有研究大规模评估NAC中的事件，这些事件是自然奖赏母体变化的基础。在这项研究中，我们利用微阵列和生物信息学方法来评估小鼠产后NAC基因表达的变化。模块化单集浓缩试验(MSET)表明，在五个独立管理的数据库(如马拉卡德、物候学)中，产后(相对于处女)NAC基因表达谱显著丰富了与成瘾和奖赏相关的基因。已鉴定出100多个成瘾/奖赏相关基因，其中包括：PER1、PER2、Arc、Hmer 2、Creb1、GRM3、FosB、GABRB3、ADRA2A、NTRK2、Cry1、Penk、Cartpt、Adcy1、Npy1r、Htr1a、Drd1a、Gria1和Pdyn。ToppCluster分析发现，与尼古丁、氯胺酮和屈诺比诺的药物作用相关的基因的母体NAC表达谱显著丰富。途径分析表明，产后NAC在RNA加工、中枢神经系统发育/分化和转录调控方面具有丰富的功能。加权基因共表达网络分析(WGCNA)发现了可能的转录因子网络，包括Nr1d1、PER2、FosB、Egr1和Nr4a1。产后状态会增加精神健康障碍的风险，MSET分析表明产后NAC中与抑郁症、双相情感障碍(BPD)和精神分裂症相关的基因丰富。与心理健康相关的基因包括：Fabp7、GRM3、Penk和Nr1d1。我们通过定量聚合酶链式反应证实了Nr1d1、PER2、GRM3、Penk、Drd1a和Pdyn。这项研究首次表明，产后NAC涉及与成瘾和奖励有关的大规模基因表达变化。由于产后状态也涉及对药物反应的降低，这一发现可能为如何减轻成瘾提供洞察力。
Motherhood involves a switch in natural rewards, whereby offspring become highly rewarding. Nucleus accumbens (NAC) is a key CNS region for natural rewards and addictions, but to date no study has evaluated on a large scale the events in NAC that underlie the maternal change in natural rewards. In this study we utilized microarray and bioinformatics approaches to evaluate postpartum NAC gene expression changes in mice. Modular Single-set Enrichment Test (MSET) indicated that postpartum (relative to virgin) NAC gene expression profile was significantly enriched for genes related to addiction and reward in five of five independently curated databases (e.g., Malacards, Phenopedia). Over 100 addiction/reward related genes were identified and these included: Per1, Per2, Arc, Homer2, Creb1, Grm3, Fosb, Gabrb3, Adra2a, Ntrk2, Cry1, Penk, Cartpt, Adcy1, Npy1r, Htr1a, Drd1a, Gria1, and Pdyn. ToppCluster analysis found maternal NAC expression profile to be significantly enriched for genes related to the drug action of nicotine, ketamine, and dronabinol. Pathway analysis indicated postpartum NAC as enriched for RNA processing, CNS development/differentiation, and transcriptional regulation. Weighted Gene Coexpression Network Analysis (WGCNA) identified possible networks for transcription factors, including Nr1d1, Per2, Fosb, Egr1, and Nr4a1. The postpartum state involves increased risk for mental health disorders and MSET analysis indicated postpartum NAC to be enriched for genes related to depression, bipolar disorder (BPD), and schizophrenia. Mental health related genes included: Fabp7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions.
登录
查看更多内容
影响因子：
3.7
作者：
Eisinger BE;Zhao C;Driessen TM;Saul MC;Gammie SC
通讯作者：
Gammie SC
影响因子：
2.4
作者：
Driessen TM;Eisinger BE;Zhao C;Stevenson SA;Saul MC;Gammie SC
通讯作者：
Gammie SC
影响因子：
7.6
作者：
Atzil, Shir;Hendler, Talma;Feldman, Ruth
通讯作者：
Feldman, Ruth
影响因子：
3.7
作者：
Driessen, Terri M.;Zhao, Changjiu;Gammie, Stephen C.
通讯作者：
Gammie, Stephen C.
影响因子：
3.6
作者：
HANSEN, S;HARTHON, C;SVENSSON, K
通讯作者：
SVENSSON, K