Scientists at Kyushu University report that turning brain immune cells into neurons restores brain function after stroke-like injury in mice. Their findings suggest that replenishing neurons from immune cells could be a potential avenue for treating stroke in humans.
The findings are published in PNAS in an article titled, “Direct neuronal conversion of microglia/macrophages reinstates neurological function after stroke.”
“Although generating new neurons in the ischemic injured brain would be an ideal approach to replenish the lost neurons for repairing the damage, the adult mammalian brain retains only limited neurogenic capability,” wrote the scientists. “Here, we show that direct conversion of microglia/macrophages into neurons in the brain has great potential as a therapeutic strategy for ischemic brain injury.”
“When we get a cut or break a bone, our skin and bone cells can replicate to heal our body. But the neurons in our brain cannot easily regenerate, so the damage is often permanent,” explained Kinichi Nakashima, PhD, a professor at Kyushu University’s Graduate School of Medical Sciences. “We therefore need to find new ways to replace lost neurons.”
One possible strategy is to convert other cells in the brain into neurons. The researchers focused on microglia.
“Microglia are abundant and exactly in the place we need them, so they are an ideal target for conversion,” said first author, Takashi Irie, PhD, from Kyushu University Hospital.
In prior research, the scientists demonstrated that they could induce microglia to develop into neurons in the brains of healthy mice. In the current study, the scientists showed that this strategy of replacing neurons also works in injured brains and contributes to brain recovery.
The scientists caused a stroke-like injury in mice by temporarily blocking the right middle cerebral artery. A week later, the researchers examined the mice and found that they had difficulties in motor function and had a marked loss of neurons in a brain region known as the striatum.
The researchers then used a lentivirus to insert DNA into microglial cells at the site of the injury. The DNA held instructions for producing NeuroD1, a protein that induces neuronal conversion. By eight weeks, the new induced neurons had successfully integrated into the brain’s circuits.
At only three weeks post-infection, the mice showed improved motor function in behavioral tests. These improvements were lost when the researchers removed the new induced neurons.
“These results are very promising. The next step is to test whether NeuroD1 is also effective at converting human microglia into neurons and confirm that our method of inserting genes into the microglial cells is safe,” said Nakashima.
Furthermore, the treatment was conducted in mice in the acute phase after stroke, when microglia were migrating to and replicating at the site of injury. The scientists also plan to see if recovery is also possible in mice at a later, chronic phase.
