Background: Major depression has a complex and multifactorial etiology constituted by the interaction between genetic and environmental factors in its development. Objective: The aim of this study was to evaluate the effects of sodium butyrate (SD) on epigenetic enzyme alterations in rats subjected to animal models of depression induced by maternal deprivation (MD) or chronic mild stress (CMS). Methods: To induce MD, male Wistar rats were deprived of maternal care during the first 10 days of life. To induce CMS, rats were subjected to the CMS for 40 days. Adult rats were then treated with daily injections of SD for 7 days. Animals were subjected to the forced swimming test (FST), and then, histone deacetylase (HDAC), histone acetyltransferase (HAT), and DNA methyltransferase (DNMT) activities were evaluated in the brain. Results: MD and CMS increased immobility time in FST and increased HDAC and DNMT activity in the animal brains. SD reversed increased immobility induced by both animal models and the alterations in HDAC and DNMT activities. There was a positive correlation between enzyme activities and immobility time for both models. HDAC and DNMT activities also presented a positive correlation between themselves. Conclusion: These results suggest that epigenetics can play an important role in major depression pathophysiology triggered by early or late life stress and its treatment.

中文翻译：

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丁酸钠的抗抑郁作用伴随着早期或晚期生活压力大鼠的大脑表观遗传调节

背景：重度抑郁症的病因复杂且多因素，由遗传因素和环境因素在其发展过程中的相互作用构成。目的：本研究的目的是评估丁酸钠（SD）对母性剥夺（MD）或慢性轻度应激（CMS）引起的抑郁动物模型大鼠表观遗传酶改变的影响。方法：为了诱导 MD，雄性 Wistar 大鼠在出生后 10 天内被剥夺母体护理。为了诱导 CMS，使大鼠接受 CMS 40 天。然后，成年大鼠每天注射 SD，持续 7 天。对动物进行强迫游泳测试（FST），然后评估大脑中的组蛋白脱乙酰酶（HDAC）、组蛋白乙酰转移酶（HAT）和DNA甲基转移酶（DNMT）活性。结果：MD 和 CMS 增加了 FST 中的不动时间，并增加了动物大脑中的 HDAC 和 DNMT 活性。 SD 逆转了动物模型引起的不动性增加以及 HDAC 和 DNMT 活性的改变。两种模型的酶活性和不动时间之间均呈正相关。 HDAC 和 DNMT 活性之间也呈现正相关。结论：这些结果表明表观遗传学可以在早期或晚期生活压力及其治疗引发的重度抑郁症病理生理学中发挥重要作用。