Today, as much as a third of the world’s population is plagued by stress-related disorders. Depression, anxiety and post-traumatic stress disorder have become increasingly prominent causes of disability and of mortality. Modern methods of intervention like medication and behavioural therapy, while effective as treatments, are far from cure-all remedies.
While the outlook appears bleak, the aptly named Team Resilieo has not been deterred in the slightest.
Dr Akshaya Hegde (first author of the paper) and Asst Prof Rupshi Mitra
Based in NTU’s School of Biological Sciences, the latest research from Team Resilieo, which consists of Assistant Professor Rupshi Mitra, Dr Akshaya Hegde and Shruti Suresh, delves into the applications of environmental enrichment as a curative approach.
Asst Prof Rupshi Mitra and Shruti Suresh in the lab
As it stands, early-life is an especially precarious time for brain development. Experiences during this period have an enduring impact on stress-response.
More specifically, stressful experiences in early-life tend to make individuals even more vulnerable to developing anxiety, depression or other stress-responsive psychiatric disorders later in life.
On the flip side, early-life also remains a favourable window for cultivating greater resilience to stress. This is where the potential benefits of environmental enrichment come in, and is what Team Resilieo is working towards – building an expansive knowledge base on the potential applications of such enrichment, especially during the early-life stage.
In a paper published on 2 August 2020 in Scientific Reports (Nature) titled Early‑life short‑term environmental enrichment counteracts the effects of stress on anxiety‑like behavior, brain‑derived neurotrophic factor and nuclear translocation of glucocorticoid receptors in the basolateral amygdala, the team narrowed in on the issue of early-life maternal-separation stress, using rat subjects to determine whether such stress could be alleviated with environmental enrichment.
Asst Prof Mitra at work in the lab
At the start of the project, from the period between 2 to 14 days after birth, the rat pups were separated from their mothers and put into different enclosures daily, for three hours. As the pups were still dependent on their mother for food, the separation simulated an instance of early-life stress. In contrast, pups in the group slated for enrichment were provided with better quality nesting materials, burrowing tubes of various sizes, enrichment toys, and fruit-flavored chow.
After 60 days, having reached adulthood, the subjects were put into a field test. An important proxy for anxiety-like behaviour is the tendency for exploration – as such, the field test was conducted using a circular arena, with the subjects placed in the center.
From there, it was observed that the enriched subjects, more so than their unenriched counterparts, were the ones venturing from the relative safety of their original positions in the arena. Across the board, the enriched subjects spent the most time exploring, exhibiting a greater willingness to inspect the exposed, open spaces of the arena than the unenriched subjects.
The field test also revealed, in a later examination of the subjects, that the enrichment process had created long lasting and tangible changes to neurons and hormones in the body.
A visualisation of the subjects’ neurons
Earlier studies by Team Resilieo have established that the growth of neurons in the amygdala is highly correlated with experiences of great anxiety. In the case of the field test, it was apparent that for all the recorded signs of stress the subjects experienced – high reluctance towards spatial exploration, increases in glucocorticoids in the bloodstream, increases in the density of their dendritic spines – there was a marked reduction in the same signs in the enriched subjects.
What Team Resilieo has discovered, in effect, is that harm derived from the loss of maternal care, or even from other types of stressors, can be mitigated with a sufficiently enriched environment.
With a sufficiently enriched environment, harm caused by various stressors can be effectively mitigated
So what does this mean for those who suffer from stress-related disorders? With the team’s demonstration that changes to early-life environments can have huge payoffs in cultivating an individual’s stress resilience, the future looks promising with the potential for more treatment options.
“Future clinical research can go even further”, Prof Mitra explains. Changes in rats’ stress receptors can be examined; counterparts in the human body can be mapped, and the information used for the eventual development of pharmaceuticals; field research could even be expanded in new ways, as rats in the wild develop differently.
As Prof Mitra enthuses, “This [paper] is just the beginning.”