As powerful as the human brain is, once it's damaged it can't really recover completely. Now researchers at Penn State may have found a way to boost the brain's regenerative abilities, using certain molecules to convert neighboring cells into new neurons. The technique could eventually lead to pills that treat brain injuries, stroke or Alzheimer's disease.
Most cells in the body can patch up damage by dividing to create new versions of themselves. But neurons lack this ability, so once they're damaged through illness or injury, there's not much that can be done. Worse still, in an overzealous attempt to protect the injured site, glial cells form scar tissue around damaged brain regions, which can reduce what little neuron growth there might be and prevent neurons from effectively communicating with each other.
With the new work, the Penn State team found that these glial cells could be put to work rebuilding the damage, rather than just getting in the way.
"The biggest problem for brain repair is that neurons don't regenerate after brain damage, because they don't divide," says Gong Chen, lead researcher on the study. "In contrast, glial cells, which gather around damaged brain tissue, can proliferate after brain injury. I believe turning glial cells that are the neighbors of dead neurons into new neurons is the best way to restore lost neuronal functions."
In past work, the researchers had found that a cocktail of nine molecules could convert glial cells into new neurons. Although it was promising, the treatment was too complicated to be very practical. So the team set out to trim the number of molecules down to a more manageable amount. In the new work, they got it down to just four.
"We identified the most efficient chemical formula among the hundreds of drug combinations that we tested," says Jiu-Chao Yin, co-first author of the study. "By using four molecules that modulate four critical signaling pathways in human astrocytes, we can efficiently turn human astrocytes (glial cells) – as many as 70 percent – into functional neurons."
In their tests on human neurons grown in culture in the lab, the researchers found that the converted neurons functioned as normal neurons would in the brain, forming networks and communicating effectively with each other. They survived for over seven months.
To see if the process could be simplified even further, the researchers also tried using just three molecules, and it also worked, albeit with a 20-percent drop in the conversion rate. Using just one molecule, however, wasn't enough to convert cells.
According to the researchers, the beauty of this work is that the molecules could potentially be packaged into a pill. Of course, it's still very early days and there's plenty of work to do to make the treatment practical and safe, but the possibility of popping a pill to repair brain damage from Alzheimer's or strokes is an enticing future.
The research was published in the journal Stem Cell Reports.
Source: Pennsylvania State University
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