Rat Study Shows Single Stressor Can Lead to Delayed Trauma

A new study with rats shows how a single instance of severe stress can lead to delayed and long-term psychological trauma.

The work pinpoints key molecular and physiological processes that could be driving changes in brain architecture, according to Indian scientists at the National Centre for Biological Sciences (NCBS) and the Institute for Stem Cell Biology and Regenerative Medicine (inStem) in Bangalore, India.

The research team, led by Dr. Sumantra Chattarji, discovered that a single stressful incident can lead to increased electrical activity in the brain region known as the amygdala.

This activity sets in late, occurring 10 days after a single stressful episode, and is dependent on a molecule known as the N-Methyl-D-Aspartate Receptor (NMDA-R), an ion channel protein on nerve cells known to be crucial for memory functions.

The amygdala is known to play key roles in emotional reactions, memory and making decisions. Changes in the amygdala are linked to the development of post-traumatic stress disorder (PTSD).

Previously, Chattarji’s research team showed that a single instance of acute stress had no immediate effects on the amygdala of rats. But 10 days later, these animals began to show increased anxiety, and delayed changes in the architecture of their brains, especially the amygdala.

“We showed that our study system is applicable to PTSD. This delayed effect after a single episode of stress was reminiscent of what happens in PTSD patients,” Chattarji said.

“We know that the amygdala is hyperactive in PTSD patients. But no one knows, as of now, what is going on in there.”

Investigations revealed major changes in the microscopic structure of the nerve cells in the amygdala. Stress seems to have caused the formation of the new nerve connections called synapses in this region of the brain, according to the scientists.

However, until now, the physiological effects of these new connections were unknown.

In the new study, Chattarji’s team established that the new nerve connections in the amygdala lead to heightened electrical activity in this region of the brain.

“Most studies on stress are done on a chronic stress paradigm with repeated stress, or with a single stress episode where changes are looked at immediately afterwards — like a day after the stress,” said Farhana Yasmin, one of the Chattarji’s students. “So, our work is unique in that we show a reaction to a single instance of stress, but at a delayed time point.”

A well-known protein involved in memory and learning — NMDA-R — has been recognized as one of the agents that bring about these changes, according to the scientists.

Blocking the NMDA-R during the stressful period not only stopped the formation of new synapses, it also blocked the increase in electrical activity at these synapses.

“We have, for the first time, a molecular mechanism that shows what is required for the culmination of events 10 days after a single stress,” said Chattarji.

“In this study, we have blocked the NMDA receptor during stress. But we would like to know if blocking the molecule after stress can also block the delayed effects of the stress. And if so, how long after the stress can we block the receptor to define a window for therapy.”

Source: National Centre for Biological Sciences
Photo: This is a pyramidal neuron. Credit: Chattarji laboratory.