Imagine your brain as a giant system of metro rail lines with trains constantly zipping through. Now imagine an earthquake crumbles many of the lines; obviously we’re talking about some sort of brain damage here such as trauma or Alzheimer’s disease. In the real world, ambulances, fire trucks and eventually construction vehicles appear on the scene to clean up the mess and get the whole system back on track.
Your brain has analogous cells as well called glial cells that appear on the scene to repair damaged neurons. But now imagine that the entire emergency response system of New York shows up for damaged lines in Queens and then refuse to get out of the way once the job is done. Sure, the damage may be somewhat repaired, but the vehicles are blocking the paths.
This is sort of what happens with glial scarring. The glial cells that support healthy neurons build up on a damaged site and don’t let any more trains pass. But researchers at Penn State hope they have found a solution. They have demonstrated the ability to convert ambulances and police cars to rail trains, freeing up the transportation system once more.
The researchers accomplished this feat using genetic engineering techniques, introducing a retrovirus to glial cells to deliver a protein called NeuroD1, which is known to be important in the formation of nerve cells in the hippocampus area of adult brains. They hypothesized that expressing NeuroD1 protein into the reactive glial cells at the injury site might help to generate new neurons — just as it does in the hippocampus.
In one test, the team showed that the retrovirus could coax glial cells into becoming functional neural cells in adult mice. What’s more, they found that two types of glial cells can be converted into both excitatory and inhibitory neurons, which is important for proper brain function. While some neurons in your brain are excitatory, passing signals on to their neighbors, others are inhibitory, telling them to calm the hell down.
In a second test, the team showed that the same could be done in adult mouse models of Alzheimer’s disease, even when the mice were 14 months old, which is 60 in human years. “Therefore, the conversion technology that we have demonstrated in the brains of mice potentially may be used to regenerate functional neurons in people with Alzheimer’s disease,” said Gong Chen, a professor of biology, the Verne M. Willaman Chair in Life Sciences at Penn State, and the leader of the research team.
Finally, Chen and his colleagues showed that the same technique could work for human glial cells in a laboratory experiment. “Within 3 weeks after expression of the NeuroD1 protein, we saw in the microscope that human glial cells were reinventing themselves: they changed their shape from flat sheet-like glial cells into normal-looking neurons with axon and dendritic branches,” Chen said. The scientists further tested the function of these newly converted human neurons and found that, indeed, they were capable of both releasing and responding to neurotransmitters.
“Our dream is to develop this in vivo conversion method into a useful therapy to treat people suffering from neural injury or neurological disorders,” Chen said. “Our passionate motivation for this research is the idea that an Alzheimer’s patient, who for a long time was not able to remember things, could start to have new memories after regenerating new neurons as a result of our in vivo conversion method, and that a stroke victim who could not even move his legs might start to walk again.”
Of course, caveats abound for projects like this. Just because something works in a mouse model does not mean it will work in an actual human brain. And even if it does, the potential side effects are numerous. And even converting excess glial cells into active neural cells likely can’t repair all of the damage done by debilitating diseases.
Can transformed glial cells actually integrate into the existing neural network harmoniously? Can they even be transformed at all? This is just a first step, and most first steps lead to nowhere. But still, it’s a cool and exciting first step nonetheless.
The paper, “In Vivo Direct Reprogramming of Reactive Glial Cells into Functional Neurons after Brain Injury and in an Alzheimer’s Disease Model,” was published in the journal Cell by Chen and his colleagues Ziyuan Guo, Lei Zhang, Zheng Wu, Yuchen Chen, and Fan Wang, all from Penn State.