A new study has shown that it is possible to turn support cells in the brain into functioning neurons that can repair damaged circuits. Researchers at King’s College London have successfully reprogrammed astroglia – cells that normally support and protect neurons – into a specific type of interneuron that is essential for controlling brain activity. By modifying a key protein, they created cells that fire at high speeds, a property crucial for preventing the runaway brain activity seen in conditions like epilepsy.
This breakthrough suggests that in the future, doctors might be able to treat neurological disorders not just by giving drugs, but by rebuilding the brain’s own wiring using cells that are already there.
How modified Ascl1 turns support cells into neurons
The human brain is made of complex circuits where neurons communicate with each other. When these circuits break down due to injury or disease, the brain struggles to fix them because it cannot easily grow new neurons. For years, scientists have tried to solve this by converting other cell types into neurons, a process called lineage reprogramming.
The challenge of reprogramming brain cells
Astroglia are abundant cells in the brain that perform housekeeping tasks, like maintaining the chemical environment and supporting synapses. Because they are already present in the brain and can divide, they are ideal candidates for conversion. However, previous attempts often failed to produce fully functional neurons that could integrate properly into existing networks.
The breakthrough: mutating the Ascl1 protein
In this new study, the research team focused on a protein called Ascl1, which is known to help neurons develop. In its natural form, Ascl1 has limited power to reprogram cells in the postnatal brain. The researchers discovered that by making specific changes to the protein – mutating six sites where the protein is normally modified by the cell – they could supercharge its activity.
This “phospho-site–deficient” version of Ascl1 acted like a master switch. When introduced into the astroglia of young mice, it efficiently converted them into neurons. Crucially, these were not just generic neurons; they developed into a specific, highly specialized type known as interneurons.
Fast-spiking neurons are key to controlling brain activity
The brain needs a balance between excitation (activity) and inhibition (quieting). If there is too much excitation, the brain can seize up, which is what happens in epilepsy. Interneurons are the brakes of the brain; they release inhibitory signals that keep excitatory neurons in check.
Why parvalbumin-positive interneurons matter
The reprogrammed cells in this study developed the hallmarks of parvalbumin-positive (PV) interneurons. These are a special class of inhibitory cells known as “fast-spiking” neurons because they can fire electrical signals at incredibly high frequencies.
This speed allows them to precisely time and synchronize the activity of large groups of neurons, stabilizing brain circuits. The researchers confirmed that their engineered neurons could fire at these high rates, proving they had acquired the complex machinery needed to function just like the natural cells they were meant to replace.
A new path for treating epilepsy and brain damage
The ability to generate fast-spiking interneurons on demand opens a new door for regenerative medicine. Many neurological conditions, including epilepsy and schizophrenia, are linked specifically to the dysfunction or loss of these PV interneurons.
Restoring balance in the brain
Current treatments for epilepsy mostly rely on drugs that dampen overall brain activity, which can cause side effects like drowsiness or cognitive slowing. This new approach offers a more targeted solution: repairing the circuit itself.
“This landmark study’s success in creating neurons from astroglia breaks new ground in regenerative medicine, offering promise for the restoration of aberrant circuitry and brain function in neurological conditions,” said Dr. Nicolás Marichal, one of the study’s lead authors.
If scientists can refine this technique to work safely in humans, they could potentially treat epilepsy by reprogramming a patient’s own local astroglia into new inhibitory neurons, restoring the balance of the brain circuit from the inside.
What you can do about it
This research is still in the early stages and has so far been conducted in mice. It will likely take years of testing before it is available as a treatment for humans.
- Stay informed: Follow updates on regenerative medicine and neuroscience to track how this technology progresses.
- Support research: Funding for basic science is what makes discoveries like this possible.
- Maintain brain health: While we wait for advanced therapies, protect your current brain circuits through regular exercise, good sleep, and a healthy diet, which are proven to support cognitive resilience.
Sources & related information
Science Advances – Reprogramming astroglia into neurons with hallmarks of fast-spiking parvalbumin-positive interneurons – 2024
Researchers demonstrated that a modified version of the Ascl1 protein can efficiently convert astroglia into functional, fast-spiking interneurons in the mouse brain, offering a potential strategy for repairing damaged neural circuits.
King’s College London – Reprogrammed brain cells could restore damaged circuits – 2024
A press release summarizing the study’s findings, highlighting the potential of lineage reprogramming to treat disorders like epilepsy by restoring specific inhibitory neurons.
JCI Insight – Parvalbumin interneuron impairment causes seizures – 2024
A related study explaining how the failure of parvalbumin-positive interneurons leads to unchecked brain excitation and seizures, underscoring the importance of restoring this specific cell type.
0 Comments