持续暴露于无定形姜黄素后大鼠海马神经源龛中 DNA 甲基化改变的基因

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Qian Tang , Ryota Ojiro , Shunsuke Ozawa , Xinyu Zou , Junta Nakahara , Tomohiro Nakao , Mihoko Koyanagi , Meilan Jin , Toshinori Yoshida , Makoto Shibutani
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引用次数: 0

摘要

从胚胎阶段就暴露于姜黄素(CUR)无定形配方的大鼠后代具有抗焦虑样行为、增强的恐惧消除学习能力以及海马齿状回(DG)突触可塑性的增强。在本研究中,我们研究了神经源龛中甲基化状态改变的基因与 CUR 暴露后神经功能增强之间的联系。我们在大鼠分娩后第 77 天对暴露于 CUR 的后代进行了 DG 甲基化和 RNA 测序分析。甲基化敏感的高分辨率熔解和实时逆转录 PCR 分别验证了候选基因的甲基化状态和转录水平。在CUR组中,我们证实了Gpr150、Mmp23、Rprml和Pcdh8的高甲基化和下调,以及Ppm1j、Fam222a和Opn3的低甲基化和上调。免疫组化显示,暴露于 CUR 后,reprimo-like+柱状细胞和protocadherin-8+颗粒细胞减少,opsin-3+柱状细胞增加。谷氨酸脱羧酶 67+ γ-氨基丁酸能中间神经元亚群上部分表达了reprimo-like和opsin-3。此外,参与原粘连蛋白-8 介导的 N-粘连蛋白内吞的基因转录水平也随着 CUR 的暴露而改变;与此同时,Ctnnb1 和 Syp 上调,Mapk14、Map2k3 和 Grip1 下调,这表明 CUR 诱导的突触可塑性增强与细胞粘附有关。总之,我们的研究结果表明,在海马神经源龛的不同神经元群中,功能不同的基因的甲基化和表达发生了改变,从而增强了暴露于 CUR 后的突触可塑性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
DNA methylation-altered genes in the rat hippocampal neurogenic niche after continuous exposure to amorphous curcumin

Rat offspring who are exposed to an amorphous formula of curcumin (CUR) from the embryonic stage have anti-anxiety-like behaviors, enhanced fear extinction learning, and increased synaptic plasticity in the hippocampal dentate gyrus (DG). In the present study, we investigated the links between genes with altered methylation status in the neurogenic niche and enhanced neural functions after CUR exposure. We conducted methylation and RNA sequencing analyses of the DG of CUR-exposed rat offspring on day 77 after delivery. Methylation status and transcript levels of candidate genes were validated using methylation-sensitive high-resolution melting and real-time reverse-transcription PCR, respectively. In the CUR group, we confirmed the hypermethylation and downregulation of Gpr150, Mmp23, Rprml, and Pcdh8 as well as the hypomethylation and upregulation of Ppm1j, Fam222a, and Opn3. Immunohistochemically, reprimo-like+ hilar cells and protocadherin-8+ granule cells were decreased and opsin-3+ hilar cells were increased by CUR exposure. Both reprimo-like and opsin-3 were partially expressed on subpopulations of glutamic acid decarboxylase 67+ γ-aminobutyric acid-ergic interneurons. Furthermore, the transcript levels of genes involved in protocadherin-8-mediated N-cadherin endocytosis were altered with CUR exposure; this was accompanied by Ctnnb1 and Syp upregulation and Mapk14, Map2k3, and Grip1 downregulation, suggesting that CUR-induced enhanced synaptic plasticity is associated with cell adhesion. Together, our results indicate that functionally different genes have altered methylation and expression in different neuronal populations of the hippocampal neurogenic niche, thus enhancing synaptic plasticity after CUR exposure.

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来源期刊
Journal of chemical neuroanatomy
Journal of chemical neuroanatomy 医学-神经科学
CiteScore
4.50
自引率
3.60%
发文量
87
审稿时长
62 days
期刊介绍: The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches. Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples. The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.
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