Researchers led by the University of California have found important neurological differences between human and mouse brains that could have implications for future neurological research.
While mouse models are used in research for treatments for neurological disorders, over 90% of drug candidates that pass mouse models fail in humans. One reason this happens is due to our lack of knowledge on the differences between astrocytes and other brain cells in both species.
Astrocytes are critical for brain development and function. The most numerous cell type in the central nervous system, they perform many tasks including supporting other neurons and controlling the blood-brain barrier and blood flow. While injury or infection can cause astrocytes to aid in the repair of the brain, they can also increase rates of inflammation, leading to neurological damage.
For the study, the researchers examined developing cells from mouse and human brain tissue, alongside cells grown in serum-free cultures from astrocytes selected using an antibody-based method.
The researchers chose to grow cells in a serum-free culture as often, serums, containing a mixture of proteins, hormones, fats and minerals, can put astrocytes in a reactive state similar to that caused by infection or injury. Being able to grow the cells without serum thus allowed the researchers to study them in a healthy state and better control for oxidative stress, oxygen levels and inflammation.
From experiments with the cells, the researchers found that mouse astrocytes are more resilient to oxidative stress than human versions. Unlike in human astrocytes, a lack of oxygen triggers molecular repair mechanisms in those of mice.
The researchers say that their findings mean that lab models using mice for neurodegeneration could be engineered to reduce astrocytes’ natural resistance to oxidative stress, thus making them more reflective of human tissues. They also said that the mouse astrocytes' ability to repair following restricted oxygen may inform new avenues for stroke research.