A research team in Italy involving two NARSAD Grantees furthered insight into the effect of stress on the brain, and what may cause malfunctions in the stress response system that can lead to impaired brain function, and ultimately depression. The body’s stress response system naturally releases hormones known as glucorticoids, such as corticosterone (“CORT”); when functioning properly, the response system has a positive effect on brain function, but when improperly functioning, it can cause long-lasting, damaging effects.

The researchers, including 2001 NARSAD Independent Investigator Grantee Maurizio Popoli, Associate Professor of Pharmacology, 2014 NARSAD Young Investigator Grantee Giulia Treccani, Ph.D.,  postdoctoral researcher, and Laura Musazzi Ph.D., research associate, all at the University of Milano, had previously shown that this stress response, and the release of CORT, increases the amount of glutamate, the brain’s main “excitatory” neurotransmitter, released in the cortex of the brain. The cortex is essential to conscious thought and memory as well as to emotional processes; neurotransmitters facilitate brain communication by transmitting signals across a synapse—a tiny gap between neurons—from one neuron (brain cell) to another. This increase in glutatmate has previously been linked to depression, but it has not been well understood what causes the system to release what becomes “too much” glutamate.

Working with rodent animal models, Drs. Popoli, Treccani and Musazzi, with colleagues, were able to parse out the contribution of the hormone CORT in disruption of the proper functioning of the system. They report that they confirm that in periods of acute stress CORT plays a definite role in increasing glutamate release; however the rapid signaling (synaptic) effects of CORT, not linked to genetic activity, are not enough to cause the long-lasting damaging effects on the brain that can lead to depression. Their work, published in April 2014 in Molecular Psychiatry, demonstrates that activation of delayed, possibly CORT-induced genetic activity is also necessary for the enhancement of glutamate release/transmission that causes the damaging effects on the brain, they say. They also found that previous treatment with an antidepressant efficiently blocked the initial rapid signaling effects of stress at cortical synapses.

Read the paper abstract.