Watering the strawberry fields of the mind
As a runner-up in our 2017 Max Perutz Science Writing Award, PhD student Sophie Quick, of the MRC Centre for Regenerative Medicine at the University of Edinburgh, explains why her research – focused on a condition called small vessel disease which can cause dementia – matters.
Strawberry picking might not seem like the place for scientific inspiration, but on a warm summers day just weeks into my PhD, I returned not just with a punnet of Scotland’s finest fruits but a new take on my research. Sheltered by a gently flapping plastic roof I bent to pluck a handful of ripe berries, spotted fine tubes running along the soil and was struck by an idea.
Our brain is just like the inside of a greenhouse, an isolated space protecting living things inside it. To keep the strawberry plants growing and maturing, the greenhouse had an irrigation system, just like the brains intricate network of tiny blood vessels that carry oxygen and nutrients to the brain cells.
Careful control of the brains irrigation system is essential as these oxygen-supplying blood vessels, or arterioles, can also carry other things that might interfere with the delicate chemical balance within the brain. Like strawberry-growers might use filtering pipes to spray water onto plants, the vessels are made of endothelial cells that only allow through water and certain molecules.
These tiny pipes threading their way around the brain can start to malfunction, and this is where my research comes in. I am interested in cerebral small vessel disease, a condition of these arterioles, the smallest of all the blood-carrying pipes. Though you might not have heard of it before, it’s surprisingly common, with a third of people over 80 showing signs. With easy-to-miss symptoms of unstable walking and forgetfulness it can only be diagnosed with MRI scans, where doctors look for a loss of brain tissue. Looking even closer, there’s narrowing and weakening of the vessels, leakage from the blood into the tissue and ultimately long-lasting damage to the brain cells. Back in the greenhouse, the irrigation pipes aren’t filtering as they should, meaning that the plants are now unable to grow any strawberries.
These damaged brain cells can lead to dementia, with small vessel disease thought to be responsible for nearly half of all dementia cases. Weakened vessels also triple your risk of stroke, which can have other serious consequences. So, tackling this disease could really improve the lives of our ever increasing aging population, the ultimate goal of my research. Specifically, I’d like to explore the sequence of events that happens as it progresses, and whether we’re able to reverse them.
Understanding the condition has already come a long way, with a new view on small vessel disease being slowly uncovered. We now think the endothelial cells lining the walls of our blood vessels might be malfunctioning. Imagine that, rather than a faulty filter, the actual plastic tubes of our irrigation system were releasing chemicals stopping the plants from producing strawberries. Well, the endothelial cells in small vessel disease look like they’re releasing molecules preventing brain cells from maturing.
To study these effects more in detail, we need to have these cells in the lab and not in the brains of patients. To do this we can use animals that mirror the condition – for small vessel disease, we use a type of rat showing the same risk of stroke, the same loss of brain tissue and even similar changes in behaviour.
One of the things we have learnt from this disease replica is that the cells have slightly different genetics to those from normal, healthy animals. Genes act as instructions and tell the cell what proteins to make, but small vessel diseased cells in these rats have a faulty instruction that means one of the proteins never gets made at all. When endothelial cells don’t make this protein, they start to fail, causing a release of chemicals that stop neighbouring brain cells from maturing.
Growing these cells in a dish lets us study what makes them malfunction and exactly what chemicals are released. It’s also possible to treat the rats with drugs we think might reverse the disease and monitor their improvement.
While it isn’t a perfect representation, one day we should be able to apply the same principles and understanding to humans. It’s like building your own mini greenhouse to practice with before making any changes to the strawberry farm.
Changing pipes in the greenhouse irrigation system would be a huge job, and replacing the brains blood vessels is simply impossible. So we need to find a way to repair the vessels inside to give brain cells the best chance of maturing. As I filled my basket with perfectly ripe berries on that uncharacteristically sunny day, I couldn’t help but wonder about the carefully controlled balance of nutrients that had guided their growth. If we can repair the pipes in the brain, we can ensure a fine crop of mature brain cells to keep our brains fruitful for longer