Understanding how certain brain cells respond to damage

Research project: Variation in astrocyte responses to different molecular pathologies and the effect on neuroprotection

Lead Investigator: Professor Stephen Wharton
Institution: University of Sheffield
Grant type: PhD studentship
Duration: 3 years
Amount: £84,953.00

Why did we fund this research project?

Comments from member of our Research Network:

‘The unknowns in this area need to be better understood. What better than a PhD studentship that also serves to prepare another researcher to join the effort to understand the diseases of the brain.’

What do we know already?

Our brain is made up of many different cells including nerve cells, astrocytes and microglia. Although Alzheimer’s disease is characterised by the loss of nerve cells, recent evidence has shown that other brain cells, such as astrocytes (support cells of the brain) also change their behaviour and may play an important role in the earliest stages of the condition.

We know that astrocytes play a part in disposing of amyloid-beta, a protein that builds up to form toxic plaques in the brain, a key hallmark of in Alzheimer’s disease. Interestingly, astrocytes can also react negatively to the build-up of amyloid-beta – losing their ability to respond to their surroundings and producing substances that can damage the brain.

Though it is clear that astrocytes behave in a complex way in Alzheimer’s, we still have a very limited understanding of their role.

This project aims to shed further light on this under-researched area.

What does this project involve?

To understand which processes astrocytes are involved in during the development of Alzheimer’s the researchers will study how astrocytes react when they are exposed to different toxic agents. 

They will be studying three different toxic agents, including different forms of amyloid beta and oxidative stress (a process that increases with ageing and can cause damage to the brain).

To do this, the researchers will take skin cells from people with Alzheimer’s and chemically reprogramme them to form astrocytes and nerve cells. These astrocytes, grown together with nerve cells, will be exposed to the toxic agents. The researchers will compare if there are differences in the astrocyte’s behaviour and in the level of support they provide to nerve cells. 

How will this project help people with dementia? 

By identifying the different pathways astrocytes are involved in after being exposed to toxic agents and how these affect nerve cells, the researchers will have a better understanding of the processes that can protect or damage the brain.
This knowledge will ultimately help us identify the pathways that can be targeted with specific drugs, encouraging astrocytes to protect nerve cells more effectively – potentially providing a new treatment for those affected by Alzheimer’s disease.