Chair and Department of Toxicology, Medical University of Lublin, 20‑090 Lublin, Poland.
Department of Biological Bases of Animal Production, University of Life Sciences in Lublin, 20‑950 Lublin, Poland.
Mol Med Rep. 2019 Mar;19(3):2386-2396. doi: 10.3892/mmr.2019.9865. Epub 2019 Jan 15.
Brain metabolism is closely associated with neuronal activity and enables the accurate synthesis and function of neurotransmitters. Although previous studies have demonstrated that chronic stress is associated with the overproduction of reactive oxygen species (ROS), which leads to oxidative stress and the disruption of glucose metabolism, the molecular mechanisms and cerebral gluconeogenesis in depression have not yet been completely elucidated. In order to examine this subject, the present study evaluated changes in the expression of selected genes involved in the glycolytic pathway and the levels of glucogenic and neuroactive amino acids in the brain of rats exposed to chronic variable stress. Male Wistar rats (50‑55 days old, weighing 200‑250 g) were divided into two groups: control and stressed, and the rats in the stressed group were exposed to stress conditions for 40 days. Depressive‑like states were observed and recorded by measuring the body weight and forced swim test (FST). The mRNA levels of Slc2a3 (coding GLUT3) and Tfam (activator of mitochondrial transcription and a participant in mitochondrial genome replication) were markedly increased, while a decrease in the expression of Ldhb and GAPDH was also observed. These modifications were associated with the redirection of glucose metabolism to appropriate defensive pathways under chronic stress conditions, and an increased ability to maintain mitochondrial function as potential adaptive responses. A marked reduction of glucogenic and neuroactive amino acids levels indicate the support of energy metabolism by stimulation of the gluconeogenesis pathway. The findings of the present study provide a novel insight into the molecular and biochemical events that impact the development of depression under chronic stress conditions, and they may identify novel targets for therapeutic intervention.
大脑代谢与神经元活动密切相关，使神经递质的准确合成和功能成为可能。尽管先前的研究表明，慢性应激与活性氧（ROS）的过度产生有关，从而导致氧化应激和葡萄糖代谢紊乱，但抑郁症中的分子机制和脑糖异生尚未完全阐明。为了研究这一课题，本研究评估了慢性可变应激暴露的大鼠大脑中参与糖酵解途径的选定基因的表达变化以及生糖和神经活性氨基酸的水平。雄性 Wistar 大鼠（50-55 天大，体重 200-250g）分为两组：对照组和应激组，应激组大鼠接受应激处理 40 天。通过测量体重和强迫游泳试验（FST）观察和记录抑郁样状态。Slc2a3（编码 GLUT3）和 Tfam（线粒体转录激活因子和线粒体基因组复制的参与者）的 mRNA 水平明显增加，而 Ldhb 和 GAPDH 的表达减少。这些变化与葡萄糖代谢在慢性应激条件下向适当的防御途径重新定向有关，并且作为潜在的适应性反应，线粒体功能的维持能力增强。生糖和神经活性氨基酸水平的显著降低表明通过刺激糖异生途径来支持能量代谢。本研究的结果为慢性应激条件下影响抑郁症发展的分子和生化事件提供了新的见解，并可能确定治疗干预的新靶点。
