Healthy brain function requires metal ions such as copper for energy production. If the brain does not have enough copper, brain damage occurs. Researchers have observed that feeding laboratory models a compound called cuprizone induces damage to the brain that is similar to MS. Most researchers believe that cuprizone binds strongly to copper, preventing it from reaching the brain. Unfortunately, definitive proof that cuprizone causes deficiency of copper in the brain is lacking, hindering research on the role copper may play in MS. One reason for this is that metal ions are “invisible” to many analytical techniques, making it difficult to directly prove that copper deficiency is occurring in regions of tissue damage.
To solve this analytical problem, Associate Professor Mark Hackett has been developing new imaging tools that enable neuroscientists to visualise metal ions in brain tissue. While metal ions are invisible to the human eye, they are not invisible to X-rays. In this project, Associate Professor Hackett’s research team will use their recently developed microscopy tools to image copper distribution in the brain of laboratory models of MS.
The results of the study are expected to reveal the specific location and cell types in the brain that exhibit copper deficiency. These discoveries will enable Associate Professor Hackett and his team to focus on particular pathways in the brain that may be influenced by copper in the context of MS.
In this project, Associate Professor Hackett and his team used cutting-edge brain imaging tools in a commonly used laboratory model for studying MS to directly visualise where copper and copper-containing proteins are found in the brain when cuprizone is administered. They discovered that brain tissue becomes deficient in copper when cuprizone is administered and the pattern of copper deficiency in the brain mirrors the pattern of demyelination.
This research provides greater understanding of this commonly used MS laboratory model. It also highlights the need for future research to investigate how a range of genetic or environmental factors could cause brain-copper deficiency in a similar fashion to the cuprizone diet. Additionally, it highlights the need to investigate therapies that target restoration of brain copper for demyelinating diseases such as MS.
Associate Professor Hackett and his team have submitted a paper to a peer reviewed journal and are preparing another two papers for publication.
Updated 31 March 2025
Professor Melinda Fitzgerald
Dr Brittney Lins
Dr Gaewyn Ellison
$25,000
2024
1 year
Current project
