Antidepressant Effect of Sodium Butyrate is Accompanied by Brain Epigenetic Modulation in Rats Subjected to Early or Late Life Stress.

Samira Silva Valvassori, Roger Bitencourt Varela, Wilson Rodrigues Resende, Taise Possamai-Della, Laura de Araujo Borba, João Paulo Behenck, Gislaine Zilli Réus, João Quevedo
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Abstract

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.

丁酸钠的抗抑郁作用伴随着受早期或晚期生活压力影响的大鼠大脑表观遗传学的调整
背景:重度抑郁症的病因复杂,由遗传和环境因素在其发展过程中的相互作用构成:本研究旨在评估丁酸钠(SD)对母体剥夺(MD)或慢性轻度应激(CMS)诱导的抑郁症动物模型大鼠表观遗传酶改变的影响:为了诱导母体剥夺抑郁模型,雄性 Wistar 大鼠在出生后的前 10 天被剥夺了母体照顾。为诱导慢性轻度应激,对大鼠进行为期 40 天的慢性轻度应激。然后对成年大鼠进行为期 7 天的每日注射 SD 治疗。对动物进行强迫游泳试验(FST),然后评估大脑中组蛋白去乙酰化酶(HDAC)、组蛋白乙酰转移酶(HAT)和 DNA 甲基转移酶(DNMT)的活性:结果:MD 和 CMS 增加了 FST 的不动时间,并提高了动物大脑中 HDAC 和 DNMT 的活性。SD 逆转了这两种动物模型引起的活动时间延长以及 HDAC 和 DNMT 活性的改变。这两种动物模型的酶活性与不动时间呈正相关。HDAC和DNMT活性之间也呈正相关:这些结果表明,表观遗传学可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。
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