Dr Yvonne Nolan is looking at how neurons grow in adult brains, and how we might be able to target them to improve health or address disease. Claire O’Connell found out more.
As you read this article, brain cells called neurons are firing bits of electrical information around inside your head so that you can read the words and make sense of them. Neurons are like information highways and they are important mediators of memory, movement and mood – and if they die in key areas of the brain in degenerative diseases, the effects can be devastating.
It used to be thought that as adults we didn’t ‘grow’ new neurons, but that view has changed, explains Nolan, who is a senior lecturer at the Department of Anatomy and Neuroscience at University College Cork (UCC).
“Up until around 20 years ago, people thought that that when neurons die they die, but now we know that as adults we can produce new neurons from stem cells in some regions of the brain, including one called the hippocampus, which is involved in memory and mood,” she says. “It’s a very new field and it’s a long way from the clinic, but the research is exploding worldwide and the potential to harness these cells to improve health or to manipulate them for neurodegenerative diseases where neurons are dying is huge.”
That’s why Nolan is co-leading a new project funded by Science Foundation Ireland with co-investigator Prof John Cryan at UCC – they hope to get a better handle on potential new drug targets and also how lifestyle interventions could prolong brain health in older age and disease.
“We are investigating the negative influences of inflammation and stress on these new neurons but also we are looking at what positive external influences, such as exercise, could possibly promote in the production of these new neurons,” says Nolan.
From molecules to behaviour
The four-year project will look at neuron growth from the perspective of molecular events happening in cells growing in the lab through to studies of a preclinical model to see how freshly minted neurons are integrated into circuits in the brain. And by exposing the developing neurons to factors associated with stress, inflammation and exercise, the UCC scientists hope to build up a bigger picture.
One of their main interests is a receptor in the nucleus of the cells called TLX, which is involved in the production of new neurons, explains Nolan. “As a group of molecules, nuclear receptors are very targetable and ‘druggable’ and we are hoping that some of our bioinformatics data that might emerge from this would be interesting to a company,” she says.
Lifestyle factors, too, are going under the microscope, including the effects of physical exercise, which is generally linked with better brain function in humans. “It’s known that physical exercise – and particularly running – increases the production of and survival of new neurons,” says Nolan. “And we also know from studies carried out in elderly populations that exercise can promote cognitive benefits. We’re interested in how exercise during early life may have positive effects on the brain in later life.”
The bigger picture of ageing in the EU
By figuring out whether and how lifestyle and potential drug interventions could be affecting the growth of new neurons, the project is tying in with a more general drive in the European Union to promote healthy ageing, according to Nolan. A recent report estimated the direct costs of brain disorders to the EU is in the region of €800bn per year, and in the context of an ageing population that figure is set to rise.
“The European Commission is putting a lot of emphasis and funding now into prevention and early intervention in brain disease and on prolonging the healthy years because of the huge costs of caring for the elderly population,” says Nolan.
She sees this as an opportunity for Irish researchers to work together in the burgeoning area of immunity and the brain. UCC was recently host to the Neuroscience Ireland conference and in May the EU conference in Dublin on Healthy Brain Healthy Europe offered a chance to see the wider picture and make connections.
“Research is better when we collaborate and see how it is going to feed into what Europe is looking at and how ultimately it is going to benefit the population as a whole,” she says.
Nolan herself has been involved in brain research for most of her scientific career, which started with a degree in biochemistry at NUI Galway, followed by a PhD in neuropharmacology between there and McGill University on how stress and inflammation affects the brain. She moved briefly to industry but quickly realised she was better suited to a career in research, so she worked with Prof Marina Lynch at Trinity College Dublin on how neurons survive during disease. From there she moved to UCC, where she has developed her research interest in how both the developing and adult brain can produce new neurons, their function in cognition, mood and movement, and how they become impaired in disease.
The new project, which kicked off last month, is in its early stages, but Nolan is excited about the prospect of answering key questions about new neurons and brain health. “We hope to work from the molecular right through to the behaviour level and to identify target genes that may have a commercial interest for developing as a drug target.”
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