Fluke Discovery Finds Mature Mouse Neurons Can Be Reprogrammed, Researchers Report

While attempting to transform a type of brain cell into neurons, researchers instead discovered they can turn mature neurons — which were previously believed to be unchangeable — into neurons that produce dopamine, the neurotransmitter that is lost in Parkinson’s disease.

The incidental discovery has therapeutic implications for Parkinson’s and other neurological conditions, according to the team at the  University of Texas Southwestern Medical Center that made the finding.

“To find that we could manipulate neurons to change their identity in adulthood was truly unexpected,” Chun-Li Zhang, PhD, a professor of molecular biology at UT Southwestern, said in a press release.

Zhang and his team published their study, “Phenotypic Reprogramming of Striatal Neurons into Dopaminergic Neuron-like Cells in the Adult Mouse Brain,” in Stem Cell Reports. 

The brain is made up of different types of cells. The most abundant of these are glial cells, which support and protect neuronal cells. They are more reactive and proliferative than neurons.

Research has shown that glial cells can be turned into neurons and form synaptic connections — specialized neuronal structures that allow neurons to communicate with each other.

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So the UT Southwestern researchers set out to transform glial cells into neurons that could produce dopamine — the substance that is lost in Parkinson’s patients and that is involved in reward behavior — by using a mix of genetic factors and a chemical compound directly injected into mouse brains.

Using a viral vector, they injected the genetic factors into the striatum, a region rich in GABA-producing neurons that helps control motor skills. Dopaminergic neurons aren’t usually located in this region, but have long extensions that control neurons in the striatum, according to the researchers.

What they found, however, was that instead of converting glial cells, they converted the mature GABA-producing neurons into dopaminergic neurons.

“We got the new cells we wanted. But, they did not originate from glial cells,” Zhang said. “Rather than originating from glia, the new dopamine cells came from local, existing mature neurons without passing through a stem cell state. This is a mature cell-to-mature cell transformation.”

The new cells retained some of the characteristics of the original cells but resemble dopaminergic neurons more closely than inhibitory neurons. The researchers now aim to fully characterize these cells in future studies.

“We were amazed. To our knowledge, changing the identity of resident and mature neurons had never been accomplished,” Zhang said.

Reprogramming adult neurons from one type into another without going through a stem cell fate was previously not thought possible. Knowing now that it can be done provides a possible therapeutic strategy for neurological diseases.