Two Irish scientists have received Galen Fellowships to study previously inaccessible parts of the brain that are thought to be crucial to two of the most devastating neurological disorders.
Dr John Waddington, a professor of neuroscience at the Royal College of Surgeons, and Dr Meenakshi Mirakhur, the head of neuropathology at the Royal Victoria Hospital in Belfast, will be working to determine how these areas affect the causes and treatments of schizophrenia and multiple sclerosis.
Schizophrenia is a psychotic illness that affects more than 15,000 people in Ireland. The disorder disturbs a number of psychological processes so that a person's perceptions and beliefs become impaired. This impairment can also cause motivational and social problems.
"A psychotic disorder is usually psychological in nature," said Dr Waddington. "What we're doing is looking for an underlying biological basis."
Dr Waddington will focus on the interaction between brain receptors and the natural brain chemical, dopamine. In the brains of those who suffer from schizophrenia, there is an overactivity of dopamine. Consequently, most medication for schizophrenia concentrates on lessening that activity.
Dopamine is a chemical messenger that allows different brain cells to communicate with each other. Dopamine is released by one cell and then travels to the surface of another. When it lands on the new cell, it is accepted by one of five types of chemical receptors. Currently, scientists do not know which cells hold which receptors, or whether there is more than one receptor on each cell. "Right now, medications for schizophrenia just turn off all five receptors in order to slow down the dopamine activity," Dr Waddington explained. "That leaves people who take the medications feeling lethargic and slow because it affects their motor skills and their emotions. However, if we can determine which of these receptors is critical to schizophrenia and which is not, we can perhaps one day create medications that turn off only the ones we need to."
For their investigation, Dr Waddington's team receives animal brain tissue from North America that has already had the genetic code for one or more of the receptors removed from the cells. His team's goal is to understand the consequences of removing the receptors from a brain cell.
"This knowledge won't just be useful for studying schizophrenia," Dr Waddington said. "There are other neurological disorders, like Parkinson's Disease, that are affected by these receptors as well."
The disruption of the blood-brain barrier, a protective layer around the brain, and its effect on MS, is the subject of Dr Mirkhur's research. Normally, the barrier acts as a filter on substances that enter the brain. However, it is thought that malfunctions in this barrier can allow inappropriate substances into the brain and lead to inflammation and the development, in certain circumstances, of multiple sclerosis.
Multiple sclerosis is a progressive disease of the central nervous system in which parts of the brain and the spinal cord tissues are destroyed. More than 10,000 people in Ireland suffer from the disease. There are a number of varieties of MS and symptoms can range from slight numbness to paralysis. Dr Mirakhur and her team are attempting to determine, by looking at the brain tissue of people who have died at various stages in the disease, when and how the bloodbrain barrier breaks down.
"We will be using new con-focal laser microscopy which will allow us to study the barrier in three dimensions," Dr Mirakhur explained. "Instead of using a light source, we will be able to pass a laser through it to pick up very small discontinuities that cannot be seen with a regular microscope."
Why the tight cells around the barrier are loosening, and when they begin to do so, is the focus of Dr Mirakhur's research. However, because the approach she is using is new and because there has not been a great deal of research done on the barrier before, getting results may take some time.