Astrocytes, the unsung stars of Parkinson’s research
In Parkinson’s research, we’re used to hearing about the dopamine-producing neurons that are lost over time. Today, on International women’s day, we look at a different type of cell, and the women researching them.
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Astrocytes are star-shaped cells found in the brain and spinal cord. They are a part of a larger group of cells known as glia. Previously glia, which means glue, were thought to simply stick and hold the all-important neurons together. We now know they have a much more expansive and important role, and researchers are exploring how they might be important in Parkinson’s.
Research has suggested that we have approximately 86 billion neurons in our brains, and anywhere from one to ten times the glia.
Astrocytes have many functions and work hard to regulate nerve cells and their environment. They provide nutrients, growth factors and chemicals to keep neurons healthy, clean up excess neurotransmitters and help repair damage in the brain and spinal cord.
Astrocytes were first linked to brain health back in the early 1900's. When studying autopsies, Ladislas von Meduna, a Hungarian neuroscientist and psychiatrist, found that people with schizophrenia or depression had less astrocytes in the outer layer of their brains.
How are astrocytes involved in Parkinson’s?
Various studies have pointed towards a role of astrocytes in the development of Parkinson’s.
Research in California showed that in the brains of people with Parkinson’s, there seem to be more astrocytes in a state of senescence — a state in which a cell can no longer divide. The researchers also found that exposure to a herbicide, paraquat, turns healthy astrocytes into senescent ones.
In a mouse model of Parkinson’s, removing these senescent cells alleviated the nerve damage and prevented the symptoms of Parkinson’s developing, which suggests that senescent astrocytes may be contributing to the development of Parkinson’s.
Researchers at Stanford University found that astrocytes can also turn into dangerous astrocytes, that can no longer protect nerve cells, and may damage them. Certain conditions can switch astrocytes into ‘reactive’ ones, which are no longer able to complete the essential jobs to keep the neurons happy. The researchers analysed brain tissue from people with Parkinson’s and other neurodegenerative conditions. They found large clusters of these reactive astrocytes in the areas most affected by the various conditions, suggesting that their formation contributes to the loss of neurons in Parkinson’s.
Women in STEM
Women are under-represented in the majority of Science, Technology, Engineering and Maths (STEM) workplaces, making up only 23% of those in core STEM occupations in the UK. Although the gap seems to be slowly closing, there is still some way to go. Women in these industries may face certain barriers, such as isolation, lack of flexible working and lack of female role models.
At Parkinson’s UK, we’re not short of role models. Here we look at two inspiring researchers exploring astrocytes in Parkinson’s.
Screening drugs to improve astrocyte function
Laura Ferraiuolo, a researcher at the Sheffield Institute for Translational Neuroscience (SITraN), exploring if the mitochondria, the energy-producing power stations of the cells, of the astrocytes might be aletered in Parkinson’s.
Mitochondria were linked to Parkinson’s back in 1989, when Parkinson’s UK funded research demonstrated that the mitochondria in the brain region affected by Parkinson’s were not functioning as they should be. Since then, researchers have been trying to figure out what causes the mitochondria to stop working and how to get them up and running again.
Laura and her team took skin biopsies from people with and without Parkinson’s. They then re-programmed these skin cells into neurons and astrocytes. They found that, compared to people without the condition, the astrocytes generated from people with Parkinson’s had more mitochondria, but that these mitochondria didn’t function as well. And without a reliable energy source, the astrocytes didn’t function well either.
Heather Mortiboys is a Parkinson’s UK Research Fellow at SITraN. Heather has screened and rated thousands of existing drugs to see if any of them might have untapped potential for Parkinson’s. She then took the top 224 ranked drugs and tested them on skin cells from people with an early onset form of inherited Parkinson’s, people with a late onset inherited form of Parkinson’s, and people with the condition who do not carry any genes known to increase risk.
On analysing the vast amount of data produced, Heather has found three groups of drugs which have beneficial effects on both the mitochondria and the lysosomes (responsible for disposing of the waste that cells produce) in skin cells from people with Parkinson’s.
Heather next wanted to investigate how these groups of drugs were protecting the mitochondria and lysosomes and find out if they have real promise as treatments. To do this she made brain cells by reprogramming the skin cells.
They have found that the drugs can increase a process where damaged mitochondria are broken down (known as mitophagy), back to normal levels in the brain cells they made. They have also investigated which mitophagy pathway the drugs could be activating.
Laura is now testing the drugs identified by Heather to see if they can also help the mitochondria in astrocytes to function better. In order to protect the neurons in Parkinson’s, it may be necessary to treat the astrocytes too.
