Rat Study Suggests Even Brief Stress Can Affect Brain

New research now shows that even a brief period of stress can cause part of the brain involved in memory to start shrinking — even before changes are evident in behavior and memory itself.

The region in question is the hippocampus, a pair of curved structures at the base of our brains. This brain region encodes memories of facts and events — names, phone numbers, dates, and daily events that we need to run our lives.

“Until now, no one actually knew the evolution of these changes. Does the hippocampus shrink before or after memory loss? Or do the two happen hand-in-hand?” said Dr. Sumantra Chattarji, one of the main investigators in this study.

To address this, an international collaborative project involving Chattarji’s group from the National Centre for Biological Sciences (NCBS) in Bangalore, India, and Dr. Shane O’Mara’s lab at Trinity College, Dublin, used rats as a model system.

The lab researched used rats as a model because they react to stress much as humans do. That is, they develop anxiety-related behaviors and their ability to form memories are affected.

Long years of research have established methods to test rats’ memories and responses to various forms of stress. This makes rats widely used models to study brain and behavior related questions.

In the current study, rats were subjected to stress for two hours every day over ten days. The rats’ brains were examined with MRI scans on several days over the course of the study, and their ability to form memories were assessed repeatedly using two different tests.

Striking results emerged in the first set of MRI scans taken after just three days of stress — the hippocampus of every stressed rat had shrunk.

“It was a totally unexpected result. Normally, structural changes are seen in the brain after a long time — say 10 to 20 days. Three days doesn’t even count as chronic stress,” said Chattarji.

Five days after stress exposure, the rats’ hippocampus-based ability to make memories were tested. Here again, the researchers were in for a surprise.

Stressed rats performed almost as well as unstressed rats.

“Volume loss and shrinkage has already happened, yet spatial memory is still holding up,” said Chattarji.

At the end of the chronic stress regime, the hippocampus of stressed rats had shrunk even more. Further, a second and different memory test performed after this scan, showed stark differences between stressed and unstressed rats. Stressed rats performed poorly in this test compared to unstressed rats.

The findings that loss of brain volume may lead to memory loss as well as detail on other interesting aspects of how the brain changes in structure during stress, are published in the journal Scientific Reports.

In the early days of stress, shrinkage in the left hippocampus is more pronounced, but at the end of 10 days, the right hippocampus loses the most volume.

“Right now, we don’t really know the functional significance of this. There is some evidence that in mice undergoing social stress, only the left hippocampus shrinks. If there is any inherent difference between the left and right hippocampus, that needs to be studied,” said Mohammed Mostafizur Rahman, a Ph.D. student with Chattarji and the lead author of the study.

Another discovery is that there are individual differences amongst the rats in how much the chronic stress regime affected them. The amount of shrinkage in a rat’s hippocampus on day three can predict the shrinkage seen at the end of the 10-day stress period. The higher the shrinkage, the worse the rats’ performance in memory tests at the end of the stress.

“This makes it even stronger that volume loss is a pretty good predictor of what the behavioral consequences will be at a much later stage,” said Chattarji.

Many different groups, including Chattarji’s have studied stress in rodent models for a long time. “What comes out in our study is that there are individual differences between rats,” said Mostafizur.

“In today’s world, with so much talk about personalized medicine, these results could have huge implications for future studies on human disease,” he said.

Source: National Centre for Biological Studies