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
Open accessAbstract
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.
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GAPDH and LDHB mRNA levels were found to be substantially decreased in MDD.
“Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase B (LDHB) mRNA levels were found to be substantially decreased in MDD. 462”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [462]
The Amino acids analysis section reports significant decreases in GAPDH and Ldhb mRNA in the hippocampus of rats exposed to chronic variable stress. The study does not establish those decreases in people with major depressive disorder (MDD), as the citing sentence implies. (LLM, conf=0.89)
Experimental — accuracy not yet measuredIn the hippocampus of depressed rats, mRNA expression of Slc2a3, which codes for GLUT3, is considerably increased.
“When the transcription of genes involved in glycolysis and glycogen synthesis was examined in the hippocampus of depressed rats, it was found that the mRNA expression of Slc2a3, which codes for GLUT3, is considerably increased. 462”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [462]
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“462 Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase B (LDHB) mRNA levels were found to be substantially decreased in MDD. 462 The transcription of genes in the brain tissues of IL18 - / - mice was examined with the use of genome-wide microarrays, and the results revealed…”
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- Authors
- Herbet, M., Natorska‑Chomicka, D., Korga, A., Ostrowska, M., Izdebska, M., Gawrońska‑Grzywacz, M., Piątkowska‑Chmiel, I., Pawłowski, K., Ślaska, B., Poleszak, E., & Dudka, J.
- Affiliations
- Medical University of Lublin (PL)
- Chair and Department of Toxicology, Medical University of Lublin, 20‑090 Lublin, Poland
- University of Life Sciences in Lublin (PL)
- Venue
- Molecular Medicine Reports
- Publisher
- Spandidos Publications
- Published
- 2019-01-15
- Volume
- 19
- Issue
- 3
- Pages
- 2386-2396
- ISSN
- 1791-2997 (ISSN-L)
- 1791-3004
- OpenAlex
- W2909069974
- Cited by
- 17
- References
- 60
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 2
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Medicine Reports (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uniwersytet Medyczny w Lublinie
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- chronic variable stress, depression, brain energy metabolism, gluconeogenesis, glycolysis, GLUT3, TFAM, mitochondrial function, LDHB, glyceraldehyde-3-phosphate dehydrogenase, glucogenic amino acids, neuroactive amino acids, adaptive response, oxidative stress
- MeSH terms
- Amino Acids, Animals, Body Weight, Brain, Depression, Energy Metabolism, Gene Expression Regulation, Glucose, Humans, Isoenzymes, L-Lactate Dehydrogenase, Mitochondria, Neurons, Stress, Psychological, Transcription Factors, Rats, Wistar, Reactive Oxygen Species, Neurotransmitter Agents, Oxidative Stress, Glucose Transporter Type 3, Rats
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