Doctoral student using Parkland Institute award for study to uncover links between prenatal stress and aging

The effects of prenatal stress can be seen across generations and Mirela Ambeskovic is studying those effects across a lifespan.

Ambeskovic (BA '12, MSc '14), a University of Lethbridge doctoral student studying under neuroscientist Dr. Gerlinde Metz, became interested in studying the effects of prenatal stress because of the influence it had on her and her family when they lived in Bosnia. Ambeskovic’s grandmother experienced prenatal stress in the aftermath of the Second World War, when shelter and food were scarce, as did her mother a generation later.

Mirela Ambeskovic is seeking to determine how prenatal stress programs the brain and behaviour across generations.

“I was a prenatally stressed baby, too. When my mom was pregnant with me, my dad went into the army. So she was home alone and had to deal with lots,” says Ambeskovic. “In a way, I feel like it maybe benefited me, building the same kind of resilience I see in the subjects we test.”

She came to Canada in 1998 after her family, including her mother and two siblings, was displaced in the Bosnian war that lasted from 1992 to 1995. She attended Winston Churchill High School and started studying biology and psychology at the University of Lethbridge a year after graduating. Two years later, she made the switch to neuroscience and got some experience working in the laboratory under Dr. Deborah Saucier, a former U of L professor of neuroscience. After she took a class on stress with Dr. Metz, she knew she’d found the field she wanted to explore further. Ambeskovic asked if Metz would take her on as a master’s student and a few days later she was in the lab.

“Everything fell into place. I stuck with it and now I’m doing my PhD. I love coming to work every day,” says Ambeskovic.

Her own stress level recently received a little reprieve when she was awarded a $5,000 scholarship through the Parkland Institute. With the financial pressure alleviated, she’ll be able to focus solely on her research.

“The main goal of my research is to determine how prenatal stress programs the brain and behaviour across generations,” she says. “I am interested in possible prenatal stress and aging interactions. I assess for cognitive and motor functions, depression and anxiety levels and brain plasticity in rats from young adulthood to middle-aged and aged.”

She studies rats over an 18-month period, equivalent to a human lifespan of 60 to 70 years. Every six months she evaluates brain and behavioural changes in the animals. Ambeskovic looks specifically at the prefrontal cortex, the area of the brain that integrates learning, memory and emotion and helps in decision-making. She also compares the effects of prenatal stress on males and females to see if any sex differences exist and whether the rats’ lifespans and susceptibility to diseases like Alzheimer’s, Parkinson’s, diabetes, kidney failure and heart failure, are affected.

In addition to a control group of non-stressed rats, Ambeskovic studies a group of rats where only the great-grandmother was prenatally stressed and not subsequent generations, and another group where all four generations experienced prenatal stress. While her research isn’t yet completed, she’s already found some results that point to the effects of prenatal stress.

“Prenatally stressed animals have a shorter lifespan and are more prone to diseases earlier in life than non-stressed individuals,” she says. “Prenatally stressed animals age faster with earlier onset of motor and cognitive deficits. Interestingly, the males are more affected than females. Females deal much better with prenatal stress than males do. Their behaviour is not as affected, nor is their brain. It actually appears that the prenatally stressed females build resilience to stress and show enhanced cognitive and motor functions.”

Not all prenatal stress is bad. Some stress is good as it prepares individuals for the environment they are born into. For instance, an animal pre-programmed to survive in a stressful environment will cope better and go on to reproduce, ensuring survival of the species, and this may have evolutionary purposes.

“It catches up to them as they get older. The organism kind of gets run down,” says Ambeskovic. “Maybe that’s why we see the difference between males and females. Males are OK when they are younger to the stage that reproduction can happen. As they get older, their bodies run down and they start giving up faster. They age faster than the females. But why females are so resilient all the time I’m not quite sure.”

In a separate study, Ambeskovic looked at the effects of prenatal stress on the emotional or mental states in young and middle-aged male rats. She found increased levels of depression and anxiety, enhanced hyperactivity and stress hormone levels in middle-aged rats. She called this cluster of behaviours exhibited by her male rats a ‘middle-age crisis’ as it resonated with similar behaviours in humans.

Ambeskovic is also looking at the epigenetic effects of prenatal stress. Certain genes, or parts of genes, may be turned on or off, depending on the environment and the rat’s experiences. For example, putting animals in an enriched environment has been shown to reverse some of the effects of prenatal stress.

“In our multi-generationally stressed animals, a lot of genes seem to be either up or down regulated and these seem to be involved in aging and immune functions, along with diabetes and depression. We need to look further into specific genes and micro-RNAs (small sequences of specific DNA) that might be changing,” she says of future studies.