Timely intervention to prevent or delay hippocampus-linked memory loss that occurs as a result of chronic stress may now be possible, thanks to the discovery of a biomarker — a reduction in hippocampal volume at an early time point after the onset of chronic stress. The reduction in the hippocampal volume is not only linked to stress-induced memory loss, it may, in fact, be an early risk factor for the eventual development of cognitive impairments. The results were published in the journal Scientific Reports.
A reduction in hippocampal volume and the consequent hippocampus-linked memory loss at the end of chronic stress is already well known both through animal studies and by studying the human brain. “So our question was different. We wanted to study how the diseases progresses and how the damage evolves over time,” says Prof. Sumantra Chattarji from the National Centre for Biological Sciences (NCBS), Bengaluru and one of the authors of the paper.
While all studies in the past have compared the effect of stress on hippocampal volume and memory loss by using two groups of animals (control and experimental group) and studying the effects at the end of the stress period, these researchers took a different approach. They studied the effects in the same animals before and at the end of the study and also at regular intervals during the course of the 10-day stress study in rats.
Rats react to stress much like humans and hence rats are used as model animals to study the effect of stress on behaviour.
“We undertook a longitudinal study for 10 days and subjected the animals to stress for two hours a day and assessed the animals’ ability to form memories. We got some surprising results,” he says. “At the end of the third day, MRI scans revealed a perceptible and significant reduction in the hippocampus volume. We did not expect to see this within three days.”
The study highlights that rats subjected to stress even for a brief period of three days is sufficient to induce damage to the hippocampus volume. Three days of stress is no where close to being labelled as suffering from chronic stress.
The second major surprise was on the fifth day of the stress. Though MRI scans of the rats on the third day revealed hippocampus volume loss, the rats did not suffer from any hippocampus-linked spatial memory loss even on day five. There was little difference in spatial memory between stressed rats and unstressed rats.
The rats examined at the end of 10 days of stress showed bigger loss of hippocampal volume on the eleventh day and also significant loss of spatial memory on the thirteenth day. “That there was significant loss of memory at the end of 10 days of stress despite no loss on day five was a surprise,” he says.
“We know from earlier work that at the end of stress both hippocampal structure and function are expected to be down. But what we find is that these two go downhill in different ways — structure goes down early and memory loss comes later — but at the end they are both down,” Dr. Chattarji says.
“That means the structural change can act as an early indicator of loss of memory that happens later. The structural deficit precedes the functional or behavioural deficit,” he says. In other words, there is a delayed manifestation of stress-induced impairment of memory loss and the full impact of stress on memory impairment becomes evident at the end of the stress.
The animals that suffered the biggest loss in hippocampal volume on the third day of stress continued to exhibit significant decrease in volume a day after the end of stress. These rats were also the ones that eventually suffered the biggest impairment of spatial memory after the end of stress.
“Right now we don’t know for how long hippocampal volume reduction and memory loss last. Clinical evidence suggests that memory loss persists for an extended period,” says Mohammed Mostafizur Rahman from NCBS and the first author of the paper. “We had earlier shown that dendrites shrink in size and other studies have shown structural changes in cellular morphology.”