How Transplanting Microglia Could Fight Age-Related Disease
Post by Anastasia Sares
The takeaway
Microglia are an important type of support cell in the brain. While mice brains without microglia can develop normally, they become severely compromised in old age. Restoring microglia can help prevent these age-related diseases in mice, paving the way for similar therapies in humans.
What's the science?
When it comes to neuroscience research, neurons are often the stars of the show. However, the brain has essential supporting actors. Cells like microglia and oligodendrocytes have a variety of roles, like aiding neuronal growth and signaling. Without the aid of these cells, neurons couldn’t do what they do. For example, microglia prune and sometimes devour other cells if they’re not pulling their weight, while oligodendrocytes wrap around the axons of neurons like the plastic around a power cord, insulating them and making the signal travel faster. They are important to the integrity of the white matter in the brain, where information is transported across long distances between different parts of the cortex. However, we still don’t fully understand the importance of these supporting cells. For example, even without the genes needed for functional microglia, some mice seem to grow and develop normally. So, what’s going on here?
This week in Neuron, Munro and colleagues showed that while mice can develop normally without microglia, their brain health takes a sharp turn for the worse in old age. However, these effects can be reversed by transplanting microglia into the brains of mice without them.
How did they do it?
This study focused on genetically modified mice that lacked a specific portion of a gene (Csf1r) that is important for microglia to form. These mice have fairly normal development, with normal levels of most other brain cells and normal performance on behavioral tests. The authors used a technique called RNA sequencing to understand how cells acted differently without microglia present. RNA is a messenger molecule carrying instructions from a cell’s DNA, a crucial step in determining which genes get made into proteins in a given cell. Different cells need different kinds of proteins depending on their function, and the cells' needs can change over time. By seeing what kinds of RNA are around in a cell, researchers can tell if the cell is functioning normally or not.
The authors collected cells from the brains of these mice and tracked RNA expression in young, adult, and elderly mice with and without their microglia to see how this expression changed as the mice were aging. They also performed other tests on the mouse brains, including scanning them with high-resolution magnetic resonance imaging (MRI), so they could detect overall changes in brain structure.
Finally, the researchers tried an intervention: they transplanted microglia into the brains of the mice who couldn’t produce them. They tracked these mice in the same way as the other two groups.
What did they find?
In young mice who were missing their microglia, the RNA profiles of most other brain cells looked normal. One exception was the oligodendrocytes, which had subtle signs of abnormal activity.
As the mice lacking microglia aged, they had increasing neurological health problems. The oligodendrocyte’s RNA profiles became even more abnormal, and other cells started showing signs of stress, producing RNA related to injury, infection, and disease. The decline could also be seen in MRI, with white matter degrading faster over time in the mice without microglia. MRI measures showed that blood flow to the thalamus was particularly affected, and the authors discovered large calcium deposits in the thalamic brain regions of these aged mice. This means that microglia play an important role in maintaining the brain’s white matter and blood flow in old age, especially in the thalamus. Interestingly, when mice without microglia received transplanted ones, they aged normally.
What's the impact?
This study shows that while microglia might not be crucial for brain development (at least in mice), they are important for helping maintain continued functioning in old age. The recovery of mice who received microglia transplants is exciting because similar therapies could be developed for humans with microglial abnormalities, potentially preventing age-related degeneration and increasing longevity and quality of life.