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In MS, immune cells attack the brain and strip the insulation (myelin) away from nerve cells. While we know a lot of how disease progresses from this point, we know very little about what causes MS to start and why the immune cells specifically attack the brain and spinal cord. A tight barrier exists between the blood and the brain called the blood-brain-barrier, or BBB. The BBB acts to keep infections as well as immune cells out of the brain. So what directs the immune cells to push through the BBB in MS?
A number of studies have shown that smoking or being overweight can increase a person's chance of developing MS, and both smoking and obesity are bad for the heart and blood vessels. This project will explore the possibility that a loss of function or loss of key cells at the BBB leading it to become leaky can result in damage to myelin inside the brain and contribute to MS initiation. In particular, Associate Professor Sutherland will examine the interaction between two cell types known as pericytes (cells found in blood vessels) and oligodendrocyte progenitor cells (found inside the brain) and explore what role these cells in combination have at the very start of MS.
The first year of this project has been mostly related to the development of the key laboratory models to complete the proposed experiments. However, there have been two key findings which may lead to some exciting discoveries. The first is a novel population of cells located on blood vessels in specific regions of the brain, that express a sensor molecule for a specific growth factor (called platelet-derived growth factor receptor-alpha). This has never been described previously and the team will conduct further studies to understand their identity, function and structure in comparison to the blood vessels of regions where they are not present.
The second finding is that loss of pericytes leads to acute and dramatic changes to the brain. This highlights the extreme importance of pericytes in the maintenance of brain function. Â Associate Professor Sutherland proposes that when this loss is coupled with an immune boost, this may give rise to MS-like pathology. Given the dramatic effects of pericyte loss on brain structure, the team proposes that pericyte loss could be important for not only MS but a number of neurological conditions.
Updated 31 March 2022
Updated: 19 January, 2021
$240,000
3 years
