Researchers have created mice containing half human brains, in an effort to understand and develop new treatments for disorders such as schizophrenia, epilepsy, cerebral palsy, intellectual disability and rare forms of dementia.
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Scientists implanted human brain cells grown in the lab into animals genetically modified to be born without a cerebral cortex or hippocampus, allowing space for human tissue to grow inside the skulls of these rodents.
This process means that scientists can now take cells from patients with brain disorders, turn them into brain tissue in the laboratory, and then implant them into living animals.
These animals can then be studied to find out how the disorder develops in human brain tissue, and how drugs can treat these conditions.
"Despite the great efforts we have made as scientists to find treatments for these diseases, psychiatry and neurology lag behind other branches of medicine, and we have fewer treatments than any other specialty," said Sergio Paschke, professor of psychiatry who led the research at Stanford University. "The reason may be that the human brain is very complex, and perhaps also because it is difficult to access. Our main goal was to make parts of the development and function of the human brain studyable."
In a previous experiment, the Stanford team implanted human nerve cells into rat brains, but the space was too limited for the growth of human tissue. To overcome this problem, the researchers genetically modified the mice to inhibit the growth of key brain regions, the cerebral cortex and hippocampus. Surprisingly, the mice survived because the remaining brain tissue took on new functions. Although the mice appear normal, they are more cautious in their gait and more forgetful.
The newborn mice received several injections of human brain tissue created from reprogrammed donor skin cells, each containing approximately 100,000 human brain cells, into the space where their brain tissue was lacking. Three months after the surgery, the human tissue connected to the mice's blood supply and filled almost the entire cavity, comprising about half the size of the rodent's brain
It is noted that human nerve cells were not organized or connected in the same way as in humans, and brain tissue was immature, equivalent to the middle of a human pregnancy.
Tests on xenocortical mice showed that the animals did not improve as a result of the implantation, but their stumbling gait and cognitive problems improved slightly
To demonstrate how these mice could help in understanding human brain disorders, researchers subjected some of the animals to five hours of oxygen deprivation. This revealed the sensitivity of human neurons to oxygen deprivation, which can cause cerebral palsy during pregnancy and birth. The researchers also discovered that the human brain tissue in the mice contained rare cells known as von Economo neurons, previously only observed in postmortem examinations. These neurons are among the first cells to die in frontotemporal dementia, a rare form of the disease. Pachka now hopes to study these mice
This work comes from the field of "neural organoids," where human brain cells grown in the lab are assembled into small but complex structures that mimic some features of the real brain. While these organoids could be revolutionary in brain medicine, they have also raised a wave of ethical concerns, not least of which are whether these tissue masses could become conscious or feel pain, and the welfare of the animals implanted with them.
Bashka said the work has been subject to intensive ethical oversight from the beginning. Experts have confirmed that this oversight should continue
Emily Jackson, professor of law at the London School of Economics and chair of a recent report on neuroorganisms for the Nuffield Council on Bioethics, notes that "animal welfare is a really important concern, and it will be necessary to monitor these animals closely to assess the impact on them
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