What Does Chronic Stress Mean at the Molecular Level?
Published March 7, 2012
For the first time, UB researchers have found proof at a
molecular level that chronic stress has a more powerful effect on
the brain during adolescence than adulthood, leading to memory
impairment and possibly triggering mental illness.
Their research, published in Neuron, shows how loss
of glutamate receptor expression and function in the prefrontal
cortex is causally linked to the negative effects of chronic
“Because dysfunction in the prefrontal cortex has been implicated in stress-related mental illness, this research will help further unravel how and why mental illnesses occur and how to treat them,” says Zhen Yan, PhD, professor of physiology and biophysics.
The UB researchers’ findings bolster an emerging understanding that the glutamate system plays a key role in mental illness and is thus critical to learning how to better treat disorders like depression, anxiety and schizophrenia.
Their study involved male rats at an age corresponding to human adolescence—a period when the brain is highly sensitive to stress.
When the rats were exposed to repeated stress, they lost glutamate receptor expression and function in the prefontal cortex, a region of the brain that controls working memory, decision-making and attention and doesn’t fully mature until age 25.
This loss significantly impaired the adolescent rats’ ability to remember and recognize objects they had previously seen.
Similarly stressed adult rats, however, did not experience the same cognitive deficit.
In their paper published on the study—“Repeated Stress Causes Cognitive Impairment by Suppressing Glutamate Receptor Expression and Function in Prefrontal Cortex”—researchers also report that by disrupting the enzymes that trigger loss of glutamate receptor expression they were able to prevent the cognitive impairment induced by repeated stress.
As a result, they have discovered that there may be a way to prevent chronic stress’ detrimental effects.
Many antipsychotic drugs currently on the market do somehow affect the glutamate system. Yan and her UB colleagues recently published an article in Molecular Pharmacology that showed how one of the newer antipsychotics, lurasidone (marketed as Latuda), does just that.
Yet a large number of these drugs also affect other important neurotransmitter systems, Yan notes.
“If, based on this research, we can begin to target the
glutamate system in a more specific and effective way, we might be
able to develop better drugs to treat serious mental
The research is especially significant because with some mental disorders, such as schizophrenia, onset typically occurs in late adolescence.
While there have been many behavioral studies about stress, understanding it at a molecular level is key to developing strategies to prevent stress-induced behavioral deficits, Yan notes.
“In the end, it has to be boiled down to molecules. Without knowing why something happens at a molecular level, you cannot do anything about it.”