Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Av. Universitária, 1105, Criciúma, SC, 88806000, Brazil.
Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Sci Rep. 2022 Jul 7;12(1):11529. doi: 10.1038/s41598-022-14660-6.
Sepsis is defined as a life-threatening organ dysfunction caused by an inappropriate host response to infection. The presence of oxidative stress and inflammatory mediators in sepsis leads to dysregulated gene expression, leading to a hyperinflammatory response. Environmental conditions play an important role in various pathologies depending on the stimulus it presents. A standard environment condition (SE) may offer reduced sensory and cognitive stimulation, but an enriched environment improves spatial learning, prevents cognitive deficits induced by disease stress, and is an important modulator of epigenetic enzymes. The study evaluated the epigenetic alterations and the effects of the environmental enrichment (EE) protocol in the brain of animals submitted to sepsis by cecal ligation and perforation (CLP). Male Wistar rats were divided into sham and CLP at 24 h, 72 h, 10 days and 30 days after sepsis. Other male Wistar rats were distributed in a SE or in EE for forty-five days. Behavioral tests, analysis of epigenetic enzymes:histone acetylase (HAT), histone deacetylase (HDAC) and DNA methyltransferase (DNMT), biochemical and synaptic plasticity analyzes were performed. An increase in HDAC and DNMT activities was observed at 72 h, 10 days and 30 days. There was a positive correlation between epigenetic enzymes DNMT and HDAC 24 h, 10 days and 30 days. After EE, HDAC and DNMT enzyme activity decreased, cognitive impairment was reversed, IL1-β levels decreased and there was an increase in PSD-95 levels in the hippocampus. Interventions in environmental conditions can modulate the outcomes of long-term cognitive consequences associated with sepsis, supporting the idea of the potential benefits of EE.
败血症是指由宿主对感染的不当反应引起的危及生命的器官功能障碍。败血症中氧化应激和炎症介质的存在导致基因表达失调，导致过度炎症反应。环境条件根据其呈现的刺激在各种病理中起着重要作用。标准环境条件（SE）可能提供较少的感官和认知刺激，但丰富的环境可以改善空间学习，防止疾病应激引起的认知缺陷，并成为表观遗传酶的重要调节剂。该研究评估了表观遗传改变以及环境富集（EE）方案在通过盲肠结扎和穿孔（CLP）引发败血症的动物大脑中的作用。雄性 Wistar 大鼠在败血症后 24 小时、72 小时、10 天和 30 天分为假手术和 CLP。其他雄性 Wistar 大鼠被分配到 SE 或 EE 中 45 天。进行了行为测试、表观遗传酶分析：组蛋白乙酰转移酶（HAT）、组蛋白去乙酰化酶（HDAC）和 DNA 甲基转移酶（DNMT）、生化和突触可塑性分析。在 72 小时、10 天和 30 天时观察到 HDAC 和 DNMT 活性增加。在 24 小时、10 天和 30 天时，DNMT 和 HDAC 之间存在正相关。在 EE 之后，HDAC 和 DNMT 酶活性降低，认知障碍得到逆转，IL1-β 水平降低，海马中 PSD-95 水平升高。环境条件的干预可以调节与败血症相关的长期认知后果的结果，支持 EE 的潜在益处的观点。
