(ORDO NEWS) — Scientists at Stanford University have for the first time integrated human neurons into the brains of newborn rats, producing fully viable adults with chimeric brains.
Such animals could facilitate the search for new methods for diagnosing and treating neurodegenerative diseases and neuropsychiatric disorders that are usually characteristic only of humans.
The development of the human brain is a non-trivial, self-organizing process as cells divide, differentiate, migrate, and connect to form vast neural networks. Subsequently, these networks are modified, improving on the basis of individual sensory experience.
The main problem on the way to a full understanding of the development of the human brain, especially in the case of the development of diseases, is the inability to work with the brain tissue of a living person.
Numerous biological models that imitate our brains in some way allow us to move in this direction. However, all of them have limited functionality, which does not allow achieving full compliance of the model with the real brain. One of the most advanced types of models is the brain organelles.
They are obtained from human skin cells converted into pluripotent stem cells, which then reverse differentiate and become various human brain cells (neurons, astrocytes, and so on).
By growing three-dimensional structures in this way, it is possible to create, for example, the organelles of the human cerebral cortex.
However, growing organoids outside the characteristic microenvironment of the real brain reduces their usefulness in modeling genetically complex and behaviorally determined neuropsychiatric disorders.
Therefore, scientists from Stanford University (USA) decided to go further and transplanted human brain organelles into the brains of newborn rats (in the first week after birth, when neural networks are still being formed).
As a result, human neurons were fully integrated into the rodent brain, forming working connections and stretching their axons (long processes) throughout the animal’s brain, and their activation could control reward-seeking behavior.
In the vast majority of animals, two months after transplantation, human organelles, fully integrated into networks of neurons, occupied about a third of the cerebral hemisphere.
A year later, 74% of the chimeric-brained rats were still alive (the typical lifespan for laboratory rats is three to four years), with no noticeable motor or memory impairments or any abnormalities at all.
At the same time, the neurons of the organoids built into the brain were much larger and had much more longer dendrites (small processes) than the standard organoid.
Scientists also noticed another important feature of these chimeric rats. In the second phase of the study, they used organoids obtained from cells from patients with Timothy syndrome, a rare genetic disease characterized by neurological defects and physical malformations, including heart problems, for transplantation.
After about six months, rats with such transplants showed characteristic signs of the disease associated with neuronal activity.
According to the authors of the work, similar experiments can be carried out using organoids obtained from the cells of people with disorders like autism or schizophrenia, and perhaps learn something new about how these conditions arise and affect the brain.
In addition, this practice will be useful for testing new treatments for neuropsychiatric disorders and neurodegenerative diseases – the main cause of disability in the world.
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