Chronic stress decreases availability of mood-regulating chemical

Chronic stress increases level of a protein that decreases availability of mood-regulating chemical – September 13, 2016 – by Toni Baker

One way chronic stress appears to cause depression is by increasing levels of a protein in the brain that decreases the availability of an important chemical that regulates our mood, scientists report.

They have found elevated levels of transglutaminase 2, or TG2, in the brains of mice experiencing chronic stress – an animal model of depression – as well as the prefrontal cortex of depressed people who committed suicide.

High TG2 levels in the mouse translated to atrophy of neurons, depression-like symptoms and reduced levels of TrkB, the receptor for brain derived neurotrophic factor, a brain-nourishing molecule that also aids connectivity, said Dr. Anilkumar Pillai, neuroscientist in the Department of Psychiatry and Health Behavior at the Medical College of Georgia at Augusta University.

They found TG2 levels increased in their animal model following administration of stress hormones and after several weeks of actual stress that mimics the lives of chronically stressed individuals. Both produced classic depressive behavior and increased TG2 levels in the prefrontal cortex, a region involved in complex thoughts, decision-making as well as mood and personality expression.

Serotonin is a major neurotransmitter in the brain involved in many functions, including mood regulation. Serotonin levels in a depressed patient’s blood should be high because serotonin signaling in the brain is low,

Astrocytes make BDNF, whose levels are also low in depression. Although just how the two work together is an unfolding mystery.

From Wikipedia: Brain-derived neurotrophic factor, also known as BDNF acts on certain neurons of the central nervous system and the peripheral nervous system, helping to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses.

In this study, Pillai and his team further linked them by showing that treatment that increases serotonin availability – as most antidepressants do – also increased levels of the BDNF receptor thru the action of RAC1. TG2 converts serotonin to RAC1, a protein that helps rejuvenate the BDNF receptor, TrkB

Now the MCG scientists have shown that in depression a healthy balance of all these is upset, as elevated TG2 makes less serotonin available, leaving insufficient levels to enable proper communication between neurons.

This may explain why depression feels so dull and slow, and even thinking becomes a huge effort.

The brain also is more vulnerable as the increased level of activated RAC1 is inexplicably degraded, which leads to less instead of more BDNF signaling.  

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