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可转移元素在中等棘状神经元中受到动态调节,可能有助于对可卡因的分子和行为适应

Gabriella M Silva¹, Amber L Kaplan¹, Celeste R Park¹

¹Department of Anatomy and Neurobiology; Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States.

Biological psychiatry

|July 27, 2025

概括

暴露于可卡因会增加核突 (NAc) 中的可转移元素 (TE) 表达,Zfp189调节这些变化. 这种转录因子会影响与可卡因使用有关的神经元适应和行为.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
遗传学是一个遗传学.

背景情况:

Zfp189,一个克鲁佩尔关联盒子 (KRAB) 指蛋白 (ZFP) 转录因子 (TF),在核 (NAc) 多巴胺D1和D2受体表达中等棘状神经元 (MSN) 中差异表达.
在暴露于可卡因后,Zfp189驱动MSN中的功能和行为适应.
本研究调查了Zfp189在可卡因适应中的作用,重点关注其可转移元素 (TE) 的调节.

研究的目的:

阐明Zfp189对NAc中可卡因适应的细胞类型特定机制.
研究可移植元素 (TE) 在可卡因的神经和行为影响中的参与.
确定Zfp189活动的操纵如何影响TE表达和MSN功能.

主要方法:

从暴露于可卡因的动物的单核RNA测序 (snRNAseq) 数据中注释了TE.
利用病毒传递的合成Zfp189转录因子 (ZFP189VPR用于激活,ZFP189WT用于抑制) 来操纵TE表达.
在暴露于可卡因后对操纵的NAc进行了批量和snRNAseq.
条件交付合成TF给Drd1+或Drd2+MSN以评估行为和细胞形态变化.

主要成果:

可卡因暴露显著增加了NAc中的TE转录表达,Drd1+MSN比Drd2+MSN更敏感.
ZFP189^VPR在很大程度上阻碍了基因表达,而ZFP189^WT和ZFP189^VPR在MSN亚型中不同调节了与免疫相关的基因表达.
对可卡因的行为和细胞形态适应被Drd1+MSN中的ZFP189^VPR和Drd2+MSN中的ZFP189^WT增强,表明一个对手过程.

结论:

作为对可卡因的反应,TE转录表达在NAc MSNs中受到动态调节.
Zfp189在调节TE表达和影响对可卡因的分子和行为反应方面发挥着关键作用.
在Drd1+和Drd2+MSN中Zfp189的对立功能有助于在暴露于可卡因后观察到的复杂适应.

关键词:

这是可卡因可卡因.吸毒成吸毒成是一种成.它的核心是accumbens的核心.转录因子的转录因子翻译学翻译学翻译学翻译学可转移的元素可以转移.

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