Researchers at the Yaksi team at the Norwegian University of Science and Technology's Kavli System Neuroscience Institute study the anatomy and function of the brain by observing the brains of zebrafish.
Cells growing along the ventricles are provided with tiny hairy projections called cilia. Little is known about cilia, but we know what happens if they stop working.
People with cilia defects may develop neurological diseases such as hydrocephalus and scoliosis.
New research from the Yaski team at the Norwegian University of Science and Technology's Kavli Institute of Neuroscience shows that cilia are essential for normal brain development.
The human brain has four fluid-filled cavities called the ventricles, all of which are interconnected. The brain is produced and filled with cerebrospinal fluid, which is continuously moving, but the specific movements are different because of what we are doing.
"There are several theories, but over the years, this fluid cycle has been thought to provide nutrients to the brain while also removing waste," said Nathalie Jurisch-Yaksi, a senior researcher at the Kavli Institute at NTNU.
"The flow of cerebrospinal fluid helps to transmit molecular signals throughout the brain," said Emre Yaksi, a professor at the Kavli Institute. It is impossible to conduct such research on humans for moral and practical reasons. Therefore, the research team chose to study zebrafish juveniles.
Zebrafish juveniles are ideal for this type of research. They are vertebrates like humans and can tell us how the human brain develops and works. In fact, zebrafish are transparent at an early age. This means that researchers can study the brain development and function of zebrafish in great detail without any intervention and without causing any pain.
“We can even investigate every cell and every cilia,” says researcher Christa Ringers.
Researchers at the Yaksi team found that cell populations with cilia are distributed in different regions of the ventricle, which together form a stable fluid and directional flow.
Heartbeat pulsation and body movement also affect the circulation of cerebrospinal fluid, but the movement of cilia seems to guarantee a stable fluid flow in a single ventricle. This flow is local, so it is mainly limited to each ventricle. But at the same time, it seems that it is necessary to separate the flow to keep the pipes open between different ventricles.
"If we stop the movement of the cilia, the catheter that connects the ventricles will close," Jurisch-Yaksi said. Fluid flow in each ventricle and fluid exchange between different ventricles depends on whether we are stationary or moving.
"As long as the fish is at rest, we find that there is very little fluid exchange between the ventricles, even if the heart beats, causing some flow between them," said researcher Emilie Willoch Olstad.
But when we move, it all changes. Exercise results in a large degree of fluid exchange between different ventricles. There are two main types of cilia, sports or non-sports, also known as primary cilia. The Yaksi team examined the movement of cilia.
Unlike most other cilia that cause fluid transfer in the human body—for example, the brush-like respiratory cilia that protects the lungs, Kavli researchers found that the cilia around the developing zebrafish's ventricles have a propeller-like form of motion, much like sperm. tail.
At the same time, cilia can also help the brain stay young and healthy. New nerve cells grow near the wall of the ventricle filled with fluid. From here, they migrate to different parts of the brain.
The differentiation of these nascent cells is thought to be influenced by nutrients and molecular signals that are transmitted through the cerebrospinal fluid near the ventricular wall.
In zebrafish, the birth of new neurons, also known as neurogenesis, occurs not only in the developing brain but also in adult fish. Recent research has shown that this happens to humans as well.
The dynamic motion of the study fluid is very complex and requires a multidisciplinary approach. Mathematicians, engineers, and physicists can help understand how ciliary movement occurs and produces flow.
The Yaksi team at the Kavli Institute is eager to work with engineers because engineers can help develop better analytical tools and computer models to study the fluid circulation in the brain. They are actively looking for people and collaborators with the right skills. Their research is far from over. The next step is to manipulate the cilia to see if it is possible to affect the brain function of the zebrafish.
For example, when cilia-mediated flow is disturbed, how will neural activity and even circadian rhythms change? Zebrafish are usually much more active during the day than at night. Does changing cerebrospinal fluid flow change the way fish perceive and react to the environment at different times of the day? These will be the next issue that the researchers plan to address.
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