Nikhil Prasad Fact checked by:Thailand Medical News Team Nov 01, 2024 1 month, 5 days, 4 hours, 43 minutes ago
Medical News: Chronic stress is a familiar challenge in today’s fast-paced world, impacting mental health and leading to conditions like depression. New research from Beijing Institute of Basic Medical Sciences and South China University of Technology suggests a groundbreaking way to combat this impact: blocking the body’s use of sugar in the brain.
Study Finds New Link Between Sugar Metabolism and Stress-Related Depression
This
Medical News report explores how scientists found that targeting glycolysis, the breakdown of glucose, can help reduce brain inflammation and depressive symptoms caused by prolonged stress. The study involved detailed experiments on mice, observing how changes in brain metabolism contribute to mental health disorders.
Chronic Stress and Neuroinflammation: A Dangerous Mix
When stress persists, it takes a toll on the brain, causing inflammation and triggering depressive symptoms. Chronic unpredictable mild stress (CUMS) in animals mimics this prolonged stress. Researchers noted that animals under CUMS conditions showed behavioral changes similar to human depression, such as reduced pleasure-seeking behaviors and increased immobility, indicating depressive-like symptoms.
The study explains that chronic stress increases glycolysis, specifically in brain cells called microglia, which are immune cells in the central nervous system. Under stress, microglia can become overactive and release pro-inflammatory molecules, leading to a harmful state of neuroinflammation. By disrupting the glucose metabolism in these cells, scientists could counteract the inflammation and its mental health effects.
The Experiment: Testing 2-Deoxy-D-Glucose’s Impact
Researchers used a compound called 2-deoxy-D-glucose (2-DG) to inhibit glycolysis in the hippocampus, a brain region essential for memory and mood regulation. They observed two groups of mice: one group experienced chronic stress and the other did not. After weeks of monitoring, they found that 2-DG successfully reduced the glycolytic activity in the stressed mice’s brains, lowering both the glucose levels and inflammatory markers.
In laboratory studies, 2-DG was added to corticosterone-treated microglia cells, a model that simulates the effect of stress hormones. This treatment showed remarkable results, as the microglia cells produced fewer inflammatory molecules, suggesting that blocking glycolysis could be a potential anti-inflammatory treatment for chronic stress-related conditions.
Observing Behavioral Changes in Mice
Behavioral assessments were key in this research. The mice underwent a series of tests to evaluate depression-like behaviors:
-Morris Water Maze (MWM): A test of spatial learning and memory, where stressed mice showed impaired learning and memory but improved with 2-DG treatment.
-Sucrose Preference Test (SPT): This test mea
sured pleasure-seeking behavior by assessing the mice's preference for sweetened water. Stressed mice had reduced sucrose intake, but after receiving 2-DG, they showed an increased preference, suggesting reduced depressive symptoms.
-Forced Swimming Test (FST): Here, researchers measured how much time the mice spent immobile, which indicates depression-like behavior. The 2-DG-treated mice were more active than untreated ones, suggesting relief from stress-induced depression.
These behavioral improvements underscore the potential therapeutic benefits of targeting glycolysis to treat mental health symptoms linked to chronic stress.
Exploring the Mechanisms: How Glycolysis Impacts Brain Inflammation
Glycolysis is a fundamental process in energy production but plays a unique role under stress conditions. In a typical immune response, cells often shift from mitochondrial oxidative phosphorylation (a more efficient way of producing energy) to glycolysis. This shift provides quick energy but also signals immune cells to release inflammatory molecules.
In the context of chronic stress, this metabolic shift in microglia appears to sustain an overactive immune response, leading to neuroinflammation and related depressive symptoms. By inhibiting glycolysis, 2-DG helps prevent the stress-induced inflammation cascade, protecting the brain’s health.
Potential for 2-DG as a Therapeutic Tool
The findings have broader implications for mental health treatment. The researchers concluded that 2-DG could offer new hope for managing depression and neuroinflammation triggered by chronic stress. This discovery is especially promising as it targets metabolism rather than neurotransmitters, which are the common focus of traditional antidepressants.
In future research, scientists hope to explore how 2-DG might be safely used in humans to treat stress-induced depression and cognitive decline. The potential for developing metabolism-based therapies opens up an exciting new avenue in the treatment of stress-related mental health disorders.
The study findings were published in the peer-reviewed journal: Brain Sciences.
https://www.mdpi.com/2076-3425/14/11/1098
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