Understanding how the Brain
19 July, 2018
* New research from MS Research Australia funded researchers has looked at mechanisms underlying nerve fibre damage and repair in MS.
* Dr Steven Petratos and his team have identified two molecules which are important in this process and have discovered that they are controlling immune cells in the brain in MS.
* These findings could be used to develop new therapies aimed at encouraging the brain to repair itself after an MS attack.
The human body is an intricate machine with all of its processes carefully regulated. This includes the number of axons a nerve cell generates, the amount of myelin on those axons and pretty much everything the body does.
Axons are the thin nerve fibres that come out of nerve cells which conduct the electrical nerve impulses around the body. Each nerve cell needs enough nerve fibres to communicate efficiently but not too many that there is confusion and chaos. In MS, after myelin is lost, nerve fibres are also damaged and this contributes to the accumulation of disability seen in progressive forms of MS.
Within the body, there are mechanisms that encourage the growth of nerve fibres and also mechanisms which block their growth. During the development and normal maintenance of the brain, these opposing mechanisms work in harmony to ensure the correct number of nerve fibres and nerve connections are made. Researchers are working out how they might be able to harness this knowledge to promote growth, and remove the blocks to growth, in order to encourage repair following damage such as that seen in MS.
Among these researchers is Dr Steven Petratos and his team from Monash University who have been funded by MS Research Australia and our partner The Trish MS Research Foundation. They have just published a study in the journal Neural Regeneration Research that sheds new light on how we might trick the body’s normal maintenance processes to enhance repair to the nervous system following an MS attack.
Dr Petratos and his team are interested in a gene in the human body called Ngr1, which has been shown to block axon growth. In this study, they used a laboratory model of an MS-like illness to investigate whether the gene was also involved in directing the activity of some of the immune and support cells, known as microglia, that are resident in the brain and are known to be important in MS.
Earlier research has shown that when the Ngr1 gene is blocked in laboratory models of MS, the disease is not so severe. In the new study, Dr Petratos discovered that this gene and another very similar gene called Ngr3 are active in the microglia cells and that both these genes are particularly active during the chronic stages of an MS-like disease.
It is known that microglia are important in helping to clear up the debris following damage in the brain. If debris is not cleared away then this can block the brain’s attempts to repair itself. This new work from Dr Petratos and his team suggests that the Ngr1 and Ngr3 genes are key players in controlling the activity of microglia. The presence of myelin debris can block the growth of nerve fibres and if the microglia don’t clear it away it could block the body’s ability to repair nerve cells.
While it has been known for a while that blocking the activity of the Ngr1 gene can prevent severe symptoms in an MS like disease, this study also implicates Ngr3 as an important gene which controls how the body cleans up the debris and helps with the repair process.
By understanding these underlying mechanisms scientists may be able to develop therapies to target the activity of these genes and encourage the body to repair nerve fibres. In turn this could prevent the accumulation of disability in people with progressive disease.
Article adapted from MS Research Australia