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急性和慢性电惊厥发作(ECS)对成年大鼠海马体中表观遗传机制的表达有不同调节作用。

Acute and Chronic Electroconvulsive Seizures (ECS) Differentially Regulate the Expression of Epigenetic Machinery in the Adult Rat Hippocampus.

作者信息

Pusalkar Madhavi, Ghosh Shreya, Jaggar Minal, Husain Basma Fatima Anwar, Galande Sanjeev, Vaidya Vidita A

机构信息

Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India (Dr Pusalkar, Ms Ghosh, Ms Jaggar, Ms Husain, and Dr Vaidya); Centre of Excellence in Epigenetics, Indian Institute of Science Education and Research, Pune, Maharashtra, India (Dr Galande).

出版信息

Int J Neuropsychopharmacol. 2016 Sep 21;19(9). doi: 10.1093/ijnp/pyw040. Print 2016 Sep.

DOI:10.1093/ijnp/pyw040
PMID:27207907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5043647/
Abstract

BACKGROUND

Electroconvulsive seizure treatment is a fast-acting antidepressant therapy that evokes rapid transcriptional, neurogenic, and behavioral changes. Epigenetic mechanisms contribute to altered gene regulation, which underlies the neurogenic and behavioral effects of electroconvulsive seizure. We hypothesized that electroconvulsive seizure may modulate the expression of epigenetic machinery, thus establishing potential alterations in the epigenetic landscape.

METHODS

We examined the influence of acute and chronic electroconvulsive seizure on the gene expression of histone modifiers, namely histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone (lysine) demethylases as well as DNA modifying enzymes, including DNA methyltransferases, DNA demethylases, and methyl-CpG-binding proteins in the hippocampi of adult male Wistar rats using quantitative real time-PCR analysis. Further, we examined the influence of acute and chronic electroconvulsive seizure on global and residue-specific histone acetylation and methylation levels within the hippocampus, a brain region implicated in the cellular and behavioral effects of electroconvulsive seizure.

RESULTS

Acute and chronic electroconvulsive seizure induced a primarily unique, and in certain cases bidirectional, regulation of histone and DNA modifiers, and methyl-CpG-binding proteins, with an overlapping pattern of gene regulation restricted to Sirt4, Mll3, Jmjd3, Gadd45b, Tet2, and Tet3. Global histone acetylation and methylation levels were predominantly unchanged, with the exception of a significant decline in H3K9 acetylation in the hippocampus following chronic electroconvulsive seizure.

CONCLUSIONS

Electroconvulsive seizure treatment evokes the transcriptional regulation of several histone and DNA modifiers, and methyl-CpG-binding proteins within the hippocampus, with a predominantly distinct pattern of regulation induced by acute and chronic electroconvulsive seizure.

摘要

背景

电惊厥治疗是一种起效迅速的抗抑郁疗法,可引发快速的转录、神经发生及行为变化。表观遗传机制参与基因调控的改变,这是电惊厥治疗的神经发生和行为效应的基础。我们推测电惊厥可能调节表观遗传机制的表达,从而在表观遗传格局中产生潜在改变。

方法

我们使用定量实时聚合酶链反应分析,检测急性和慢性电惊厥对成年雄性Wistar大鼠海马体中组蛋白修饰因子(即组蛋白乙酰转移酶、组蛋白去乙酰化酶、组蛋白甲基转移酶和组蛋白(赖氨酸)去甲基化酶)以及DNA修饰酶(包括DNA甲基转移酶、DNA去甲基化酶和甲基-CpG结合蛋白)基因表达的影响。此外,我们还检测了急性和慢性电惊厥对海马体中整体及残基特异性组蛋白乙酰化和甲基化水平的影响,海马体是一个与电惊厥治疗的细胞和行为效应相关的脑区。

结果

急性和慢性电惊厥主要诱导了独特的,在某些情况下是双向的组蛋白和DNA修饰因子以及甲基-CpG结合蛋白的调控,基因调控的重叠模式仅限于沉默调节蛋白4、混合谱系白血病蛋白3、含JmjC结构域的组蛋白去甲基化酶3、生长停滞和DNA损伤诱导蛋白45β、DNA去甲基化酶2和DNA去甲基化酶3。除了慢性电惊厥后海马体中H3K9乙酰化显著下降外,整体组蛋白乙酰化和甲基化水平基本未变。

结论

电惊厥治疗可引发海马体内多种组蛋白和DNA修饰因子以及甲基-CpG结合蛋白的转录调控,急性和慢性电惊厥诱导的调控模式主要不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/62b85f683976/ijnppy_pyw040_f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/08c8f36ab800/ijnppy_pyw040_f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/52e0b6a7cc30/ijnppy_pyw040_f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/4cf0ab28b8c8/ijnppy_pyw040_f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/20a71cf20820/ijnppy_pyw040_f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/62b85f683976/ijnppy_pyw040_f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/08c8f36ab800/ijnppy_pyw040_f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/52e0b6a7cc30/ijnppy_pyw040_f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/4cf0ab28b8c8/ijnppy_pyw040_f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/20a71cf20820/ijnppy_pyw040_f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f81e/5043647/62b85f683976/ijnppy_pyw040_f0005.jpg

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