How could stress lead to depression?

In her PhD, Annapoorna P. K. studies how stress affects the brain and how this could contribute to depression.

At first, it seemed to be an ordinary mother-to-daughter gift. Annapoorna P. K. was 14 years old when her mother gave her the book Outbreak, a novel about Ebola epidemics in the USA. Reading the book was a life-changing experience though. “My interest in science was there forever. But in India, when you say you like Biology, people just tell you to study Medicine”. So the book made her realize there was more out there for those who like natural sciences. Thus, by the 12th grade, after the book and some research about the scientific career, she already decided she wanted to become a scientist.

And like the main character of Outbreak, Dr. Marissa Blumenthal, Annapoorna initially wanted to become a microbiologist. So she did a Bachelor’s and Master’s in Biotechnology at the University of Mumbai and University of Baroda, respectively. But with time she realized she was more interested in something else. In particular, one activity was very influential for her future studies. “During my Master’s, we had a grant writing activity and I picked the topic of X chromosome inactivation and susceptibility to mental disorders”. From this experience on, she knew she wanted to study mental illnesses more in depth.

Annapoorna presenting her work in a talk.

In 2017, she started a Ph.D. in Biological Sciences, with a focus on Neuroscience, at the Center for Cellular and Molecular Biology, in Hyderabad, India. Since then, she has been studying the effects of stress in the brain and its contribution to mental illnesses. “It is common knowledge that extreme stress can have serious consequences, both physical and psychological. But what most people don’t know is that stress can actually change the brain at the cellular and molecular level”, explains the scientist.

One consequence stress may have is the increased chance of developing depression. This mental illness is characterized by frequent and long-lasting sad feelings, loss of motivation and pleasure, irritability, changes in sleep and eating habits, among others. Depression currently affects more than 260 million people worldwide and, in extreme cases, can lead to suicide. Despite many important studies done so far to understand this disorder, scientists are still studying what exactly happens in the brain that leads to depression.

Source: Our world in data.

And this has been the focus of Annapoorna’s Ph.D. work. The Indian scientist wants to understand the biological factors that mediate the effect of psychological stress on the brain and how this may contribute to the development of depression. She specifically studies molecules that change the way DNA is used to produce proteins inside our cells.

Let’s think about DNA as a cookbook. Cells use a set of specialized molecules to read this recipe book and produce the needed proteins. But different types of proteins are required depending on several aspects, such as the cell type, age, and health status. So something needs to change the way the DNA is read in these different situations. And this is where epigenetics factors appear. They act like bookmarks in the cookbook, highlighting the pages that should be read to produce the proteins needed in a specific case.

These bookmarks are sensitive to changes in the environment, including stress. And this can lead to the production of a completely different group of proteins. Thus what it is consumed and experienced by an organism may change the epigenetic marks around its DNA and influence the way the cells function. But, as Annapoorna explains, “they affect our genes extrinsically but don’t change anything within the DNA”. With this in mind, the researcher and her coworkers study how a set of molecules that act editing these epigenetic bookmarks is affected in stress and depression. “My colleagues and I work with these factors which get modulated in response to stress and contribute to the development of depression. Since they can affect several genes, they cause many changes in the neurons and ultimately the brain”.

Annapoorna in a day at the lab.

Annapoorna particularly works on one type of protein that edits the epigenetic bookmarks in the DNA, the histone lysine demethylase. “We are trying to understand the factors that work at the micro-level, inside neurons. Since it is not possible to probe into the brain tissue of humans to gain insights into the stressed brain, we make use of mouse models. We model depression in mice by using stress paradigms and behavioral tests. We then look at specific brain regions that are known to be involved in depression”. One of the brain areas that are related to depression was previously studied at her lab. This work investigated the levels of the epigenetic editing proteins in a region related to the brain reward system, the nucleus accumbens. And their results suggested that these molecules may be associated with stress-induced depression in mice. Now, at her own project, Annapoorna focuses on another brain region, involved in memory and emotional regulation, the hippocampus. As her work hasn’t been published yet, her results can’t be shared at the moment. However, the researcher has found promising preliminary data, and we’ll hopefully be able to have access to it soon.

In addition to science, in her free time, she enjoys dancing, singing, and writing, both scientific stories (links to her articles can be found below) and poems. She is also politically engaged and advocates for mental health awareness, gender equality and LGBTQ+ rights, especially in academia. Of note, she is part of an Indian initiative to broadcast the work of Indian female neuroscientists, NeuroFemIndia.

Thank you very much, Annapoorna, for sharing your story with us. Long-life to your great work on unraveling the neurobiological basis of depression. As well as, to your important work in making academia a fairer and more sensitive environment.

You can follow Annapoorna’s career here and here.

Annapoorna science communication articles:

One Brain, Many Moods: How does it all Happen?

What Lies Ahead for Indian Researchers Post COVID-19?

IndiaBioscience blog

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