Researcher Highlights
An objective analysis of the impact of stress

A fascination with human biology and the desire to understand how the body works led Dr Lin Kooi Ong to biomedical science – and now neuroscience where he’s exploring the impact of stress on our health.

As Lin was concluding his undergraduate degree in biomedical science he connected with Professor Peter Dunkley who was the inspiration who honed Lin’s interest in the workings of the brain. Working with Peter first on his Honours year, and then his PhD, Lin’s fascination with the way that the brain works has driven him to specialise in neuroscience research.

“A lot of the basic science about the brain is still unexplored and unknown. We know it’s there, but what’s really happening in the brain with its network and cells all the way to the molecular level?” Lin asks.

With his research, Lin is focused on an increasingly common 21^st century health problem – persistent stress. “A lot of people will say ‘Oh, I’m so stressed!’ but, as a neuroscientist with a biochemistry background, I’m really interested in defining what stress is and how it impacts on our health and wellbeing.”

Lin explains that the concept of stress can be confusing as the term is often used interchangeably with distress. “Stress, in a biological way, is the destruction of homeostasis – it impacts on our cell balance. Whereas distress is more of an emotionally unpleasant feeling.”

“As a scientist, I like things to be objective,” Lin says. “We need to be able to classify something such as a physical stressor: which is any threat which has a direct effect on your body or your cells.”

Lin’s research is exploring the parts of the brain which are activated during stress: primarily the catecholaminergic systems such as the locus coeruleus, the ventral tegmental area and the substantia nigra. These neurons transmit dopamine, noradrenaline and adrenaline as chemical messengers or neurotransmitters. “When you are stressed different parts of the brain region get fired up and stimulated. In the short term there are benefits to this, it keeps us alert and prepared for any danger,” Lin explains.

However, when stress is prolonged the effects on the body can be detrimental. During a period of stress the heart rate and blood pressure can be elevated and we get an adrenaline rush. “A small amount of stress is positive, it can improve our resilience and make us adapt to the next stressful event. But if the stress or distress load is high and it remains so for a long time, then it starts to shut down our body system.”

The potential health outcomes associated long-term stress are bleak, with stroke, heart disease and even Parkinson’s disease linked to long-term stress.

Could stress be a risk factor for Parkinson’s disease?

In late 2016 Lin and his team published results from a study linking stress to the development of Parkinson’s disease. With many neurodegenerative diseases, around five – ten per cent of the risk is due to genetic factors, but the remaining 90 per cent is due to idiopathic or unknown factors. “What’s causing the neurodegeneration is still unexplored and researchers are still trying to tease out what are the main components that really cause the brain to slowly die off.”

Taking literature from military doctors who documented Parkinson’s-like symptoms in soldiers after the war, Lin and the team recreated this in the lab through inducing mild stress in mouse modelling. The results showed that after six weeks parts of the brain starts to die off. “This part of the brain controls the motor functions so it’s an important discovery,” Lin adds.

“We think that chronic stress would be a potential risk factor for the development of Parkinson’s disease. It’s not surprising, because while 20 or 30 years ago a lot of neurodegenerative diseases only occurred in people aged over 60, but now it’s getting pushed earlier to around 40-years-old.”

“Age is always a risk factor for neurodegenerative diseases and many other diseases. As you age your body replenishes itself more slowly and all the biological systems get slower. But when you chronically stress the body for long enough the ageing process gets shifted to a younger age,” Lin explains. “So it’s not surprising to see younger people getting stroke, developing hypertension, Parkinson’s and dementia.”

Stress and stroke

The impact of stress on stroke is another area that Lin’s working on because not only does stress have an effect on increasing the risk of stroke, but it can also play a role in making rehabilitation even more difficult.

“One of the things that our lab is doing is using two-way Translational Research to use basic science to investigate what happens in the clinical population, fit it back into basic scientific modelling to investigate potential therapeutic responses, then move it forward to the human population,” Lin says. “So basically moving from bench, to bedside, and bedside to bench. Back and forward.”

Over the course of last few years, Lin and his team used preclinical models to replicate ongoing stress in brain repair after stroke in humans. “We have published many critical preclinical studies (Sage 2016, Sage 2017, Neuroscience 2017) providing evidence that chronic stress is bad for stroke recovery.”

“Excitingly, we are also working on a number of potential therapeutic interventions for stroke recovery. While in their early phases, these interventions, appear to promote neuroplasticity and ameliorate post-stroke cognitive decline.”

It’s hoped that this work will allow the team to develop enough evidence-based research to allow them to move forwards in the public health sphere. One option is through the development of public health campaigns for stress reduction, something Lin feels could be very useful.

Collaborations and ‘hair-brained’ ideas

The NHMRC Centre for Research Excellence in Stroke Recovery and Rehabilitation and the John Hunter Hospital Charitable Trust support Lin in developing and validating a way to measure stress load in an objective and very non-invasive manner – through hair! “One of the things about the stress hormone, cortisol is that it’s deposited in hair, we can extract and measure its levels,” Lin says. “If we take the average hair growing speed, which is around a centimetre a month, this allows us to look at stress periods in a retrospective way.”

“This is a more objective way of measuring stress than asking volunteers in a questionnaire – and also removes limitations around memory and recall,” Lin explains.

We are now working with the Hunter New England Area Health service, in collaboration with researchers at the Florey Institute, to implement the first longitudinal study of stress levels in stroke survivors using an objective biometric evaluation. This work aligns well with the new HMRI Stroke Register where the leading stroke researchers in the Hunter can work with volunteers who are prepared to collaborate with our researchers who are looking to understand stroke.

Lin is collaborating with a range of leading researchers in the Hunter such as Professor Michael Nilsson, Associate Professor Rohan Walker, Associate Professor Coralie English, Associate Professor Phillip Dickson and Professor Deb Hodgson on a wide array of projects around stroke and neuroscience. “We are so lucky to have all these inspiring leaders in our university,” Lin says. “We need to think big and collaboration for leading change in medical research.”

As an early career researcher, Lin’s passionate about ensuring promoting the work that our ECRs do, particularly in the community. Lin is Early Career Researcher Representative for the School of Biomedical Science and Pharmacy Research Committee and was previously the Deputy Newcastle Convenor of the Australian Society for Medical Research (ASMR). “This group of researchers need to be promoted so that government, the public and institutions can see the valuable work they’re doing and keep that work in Australia.”

“I’m a big fan of this quote from the Australian of the year, Professor Alan Mackay-Sim, ‘We must invest in young scientists,’” says Lin.

Also passionate about funding, Lin can see the evidence of public donations from the community in the work our researchers do at HMRI. “Sometimes even a small donation can spark a breakthrough and lead to real changes in health and wellbeing,” Lin concludes.