肌醇对创伤性脑损伤的长期影响:表观基因组和转录组研究

IF 2 Q3 NEUROSCIENCES
Nino Oganezovi , Vincenzo Lagani , Marine Kikvidze , Georgi Gamkrelidze , Lia Tsverava , Eka Lepsveridze , Kevin M. Kelly , Revaz Solomonia
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引用次数: 0

摘要

背景和目的创伤性脑损伤(TBI)及其后果仍然是神经病学面临的巨大挑战。创伤性脑损伤的后果与大脑中的各种改变有关,但人们对表观遗传 DNA 甲基化模式的长期变化知之甚少。此外,对于能以有益方式改变这些表观遗传变化的潜在治疗方法也一无所知。因此,我们研究了肌醇(MI),它对几种病理情况都有积极作用。一组 CCI 动物接受为期两个月的生理盐水注射(TBI+SAL),另一组 CCI 动物在同一时期接受 MI 治疗(TBI+MI),还有一组作为假手术对照。小鼠在 CCI 4 个月后处死,并检测 DNA 甲基组和转录组的变化:(i)提供了CCI后海马DNA甲基化长期变化的综合图谱;(ii)确定了不同组间甲基化位点的差异;(iii)描述了转录组变化的特征;(iv)提供了DNA甲基化位点与基因表达之间的关联。MI治疗与涉及免疫反应和炎症的33个生物过程的基因上调有关。为了支持这些发现,我们发现在 BATF2 基因去甲基化的 TBI+MI 组海马中,参与免疫调节网络的转录因子 BATF2 的表达上调。通过调节免疫反应和炎症的生物通路,MI 治疗对这些过程有显著影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies

Background and purpose

Traumatic brain injury (TBI) and its consequences remain great challenges for neurology. Consequences of TBI are associated with various alterations in the brain but little is known about long-term changes of epigenetic DNA methylation patterns. Moreover, nothing is known about potential treatments that can alter these epigenetic changes in beneficial ways. Therefore, we have examined myo-inositol (MI), which has positive effects on several pathological conditions.

Methods

TBI was induced in mice by controlled cortical impact (CCI). One group of CCI animals received saline injections for two months (TBI+SAL), another CCI group received MI treatment (TBI+MI) for the same period and one group served as a sham-operated control. Mice were sacrificed 4 months after CCI and changes in DNA methylome and transcriptomes were examined.

Results

For the first time we: (i) provide comprehensive map of long-term DNA methylation changes after CCI in the hippocampus; (ii) identify differences by methylation sites between the groups; (iii) characterize transcriptome changes; (iv) provide association between DNA methylation sites and gene expression. MI treatment is linked with upregulation of genes covering 33 biological processes, involved in immune response and inflammation. In support of these findings, we have shown that expression of BATF2, a transcription factor involved in immune-regulatory networks, is upregulated in the hippocampus of the TBI+MI group where the BATF2 gene is demethylated.

Conclusion

TBI is followed by long-term epigenetic and transcriptomic changes in hippocampus. MI treatment has a significant effect on these processes by modulation of immune response and biological pathways of inflammation.

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来源期刊
IBRO Neuroscience Reports
IBRO Neuroscience Reports Neuroscience-Neuroscience (all)
CiteScore
2.80
自引率
0.00%
发文量
99
审稿时长
14 weeks
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