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The Humane Research Trust is funding a research project to advance understanding of the causes of neurological conditions. Researchers at the University of Aberdeen are using cutting-edge technologies to test how genes affect how the human brain develops. This research will help us understand how brain development works in humans and the genetic component of conditions that affect the brain.
Neurological conditions are those which affect the brain and central nervous system. There are many types of neurological condition, including neurodevelopmental and neurodegenerative conditions.
Neurodevelopmental conditions manifest in childhood and consist of variations in brain development and functioning. This group includes autism spectrum conditions, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Contrastingly, neurodegenerative disorders cause a decline in previously-held cognitive abilities. This group includes conditions like Alzheimer’s disease and Parkinson’s disease.
To understand the conditions that can impact our brains and nervous systems, we must understand the role of the cortex. The cortex is the part of the brain involved in higher-order brain functions, including sensory, motor, and cognitive processes. As humans evolved, our cortexes got bigger, resulting in our species having an increased cognitive and intellectual ability.
Research suggests a link between structural abnormalities on the cortex and the development of such neurological conditions. However, to further understand what causes these conditions, we need to uncover the mechanisms responsible for cortical development in humans.
Neurological research often involves animals such as mice. However, the developing human cortex uses specific neural stem cells which are not present in other animals, including rodents. These cells, called outer radial glial cells (oRGCs), play a key role in cortical development. They are responsible for the expansion of our brains, as they generate neurons in the upper layers of the cortex. As a result, animal models are of limited use in research about human-specific neurological disorders.
The Humane Research Trust is currently funding a project at the University of Aberdeen which uses a human model to advance neurological research. The research is being led by Dr Eunchai Kang, who believes that animal models are insufficient in this area of research. “To study human cortical development, it is essential to use a human brain model system. Rodent models do not mimic the cellular structure and developmental process of the expanded human cortex,” said Dr Kang.
Instead, Dr Kang and her research group are using cell culture systems to grow human brain organoids in a lab. These organoids contain the key neural stem cells found in a real human cortex. Researchers can then replicate the process of cortical development, using these lab-made organoids. In particular, the research group is using a technique known as CRISPR gene editing to delete genes within the organoid. This is helping them understand how the presence or absence of specific genes affects the behaviour of human brain cells.
“Identifying molecular mechanisms that control neural stem cell behaviours will help us understand human brain development,” said Dr Kang. “In addition, the research will generate insights into potential interventions and therapeutics for neurodevelopmental disorders.”
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