For the first time, a cocktail of drugs has been used to make new neurons in the brain. If the research, in mice, translates to humans, it could give us ways to repair the brain in Parkinson’s and Alzheimer’s disease, or after a stroke or brain injury.
The brain is notoriously bad at regenerating lost tissue. Although many other tissues and organs renew themselves throughout our lives, adult brains simply do not grow new neurons – or so we used to think. We now know that some brain regions do seem to keep forming a very small number of neurons later in life, but that’s about it. This means that any damaged or destroyed brain tissue is lost for good, leaving us with few options for repair.
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at Peking University Health Science Center in China and his colleagues may finally have changed that. They have developed a mix of drugs that, when injected into the brain, seems to turn support cells into new, active neurons capable of connecting with other cells.
Their cocktail targets astrocytes, star-shaped cells that support neurons and brain function. These are a useful source of potential neurons, says Deng, because they are both resilient and plentiful. “There are 10 times more astrocytes than neurons, and while neurons die in stroke, the astrocytes around them survive,” he says.
The chemicals in the cocktail activate genes that effectively erase a cell’s identity and establish a new one, says Deng. In their latest study, the team tried the cocktail in living mice. Around eight weeks later, when they analysed slices of their brains, they found that between 80 and 90 per cent of the astrocytes at the injection site had started to resemble neurons (bioRxiv, doi.org/cpmm). The cells had changed shape, showed changes in gene activity, and sent electrical signals in the same way as regular neurons, says Deng.
He doesn’t yet know how close to normal neurons these cells are. “They are unlikely to be a 100 per cent match,” he says. But the treatment seemed to be safe – the mice still had a good mix of neuron types, and none of the animals developed health problems, he says.
“If it holds up it’s absolutely amazing, and has a lot of potential applications and exciting consequences,” says at King’s College London. “If you’ve got a degenerating brain, for example in Alzheimer’s disease, and you could get the brain to regrow neurons itself, it would be a huge step forward.”
The researchers are planning to test the cocktail in mice that have had a stroke. They hope that the drugs will allow nearby astrocytes to become neurons and aid recovery.
If it works, then the cocktail offers some hope of replacing the neurons destroyed in Alzheimer’s and other neurodegenerative diseases like Parkinson’s. But it will be difficult to predict the effects the treatment could have in humans, says Grubb. Although it might restore the ability to form new memories, for example, it is unlikely to bring back lost ones.
Another challenge will be the sheer number of cells lost in neurodegenerative diseases, says at the University of Cambridge. “In Parkinson’s, a quarter of a million cells are lost from either side of the brain.” Barker has been trialling implants of brain tissue taken from aborted fetuses as a treatment for Parkinson’s.
Before Deng’s approach can be trialled in humans, we have to be sure we know exactly what types of neurons it is likely to create, says Grubb. For example, making too many neurons of the type that excites their neighbours could trigger epilepsy, he says. What’s more, different types of neurons would be required to treat each brain disorder – Parkinson’s, for example, particularly involves the death of neurons that make the chemical dopamine.
If the treatment can be used to boost grey matter in certain areas of healthy brains, it may also provide a way to improve skills like memory, although this would probably carry risks. “The chance of this being dangerous is greater than the potential benefits,” says Grubb. “You’d have to have extremely good control over what cells you’re programming, where they’re going to go, and which cells they’ll connect to.”
This article appeared in print under the headline “Adult brain coaxed to grow neurons”
