Altered expression of genes involved in brain energy metabolism as adaptive responses in rats exposed to chronic variable stress; changes in cortical level of glucogenic and neuroactive amino acids

Abstract

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.

CD103 Deficiency Promotes Autism (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) Behavioral Spectra and Reduces Age-Related Cognitive Decline

“…Human ASD, for example, exhibits increased synaptic density that can be reflected in increased synaptic relative to neuronal markers (31). In addition, increased oxidative stress in brain is characteristic of both ASD and ADHD in patients (32,33), and can be reflected by down-regulation of oxidative metabolic proteins such as GAPDH (34). Moreover, overexpression of transcriptional regulatory proteins such as eIF4E are sufficient to promote verified ASD-like behaviors in mice (35,36).…”

Evidence for a role of the basolateral amygdala in regulating regional metabolism in the stressed brain

“…2 Stress can disrupt energy homeostasis by altering major metabolic processes such as hormone signaling and glucose uptake, 3 as well as alter gene expression related to glucose metabolism and reduce glucogenic and neuroactive amino acids. 4 Other evidence has shown that stress 5 increases consumption of fat-derived ketone bodies in the brain that varies across regions. 5 However, these studies focused on stressed-induced alterations of brain metabolism in the context of the general effects of stress on metabolic processes, and the subjects in these studies were passive recipients of stressful manipulations.…”

Rosiglitazone Mitigates Dexamethasone-Induced Depression in Mice via Modulating Brain Glucose Metabolism and AMPK/mTOR Signaling Pathway

“…The frontal brain and hippocampus of depressed mice showed greater glucose/glycogen, and glucose transporter (GLUT1–GLUT3) levels than healthy animals due to the intensity of glucose uptake during depression [ 15 ]. A previous study examined the expression of glycolysis and glycogen-related genes in the hippocampus of depressed rats, and the results showed that the mRNA level of Slc2a3 (encoding GLUT3) increased [ 16 ]. According to certain hypotheses, the risk of developing mental, metabolic, and cardiovascular disorders is elevated by prolonged stimulation of the hypothalamic-pituitary-adrenal (HPA) axis.…”