MultiPark- Multidisciplinary neuroscience research at Lund University’s Post

Transcript

I believe that this will be a future therapy for neurological disorders. A new way to cure neurological diseases like Alzheimer's, schizophrenia and epilepsy may just be the result from something that started out as a failure, because being able and daring enough to think in new ways and rethink things is extremely important for researchers like Daniella Rylander Ottosson. I went on joining a team that was focused on generating new dopaminergic neurons that are implicated in Parkinson's disease, and we used reprogramming strategies for that. But that experiment did not end up as I planned. In order to produce a specific new cell, Danielle targeted what are known as support cells. In this case, she used glial cells, which are plentiful in the brain. The plan was to reprogram the cells with a new genetic code, with the help of a benign virus. The new genes were introduced into the brain of a mouse. The idea was then that the rest would take care of itself in a chain reaction. But it was at this moment that something completely unexpected happened. The cell that Daniella intended to transform in the mouse's brain didn't. Instead, it was a completely different cell, an interneuron called parvalbumin. I was very surprised by these results. And I told my student that we had to redo the experiment and try a different gene combination. But whatever gene combination we tried, we never ended up with the dopaminergic neurons. And instead we got these parvalbumin interneurons. So the glial cells seem to have a tendency to be reprogrammed into interneurons. Daniella couldn't quite let go of this discovery, so now she's letting the cell lead her forward. This opened up a completely new field of research for me that I was not aware of before I started. But when I read up on the literature, I understood that this little cell was really a hot topic. Other researchers had recently discovered that the cell appeared to be linked to several neurological diseases. So Daniella actually changed her field of research and assembled a completely new team that would solely focus on the parvalbumin interneuron. Thus began the hunt to find a treatment method for Alzheimer's, epilepsy, and schizophrenia. Our brains are full of different nerve cells with different functions. The parvalbumin cells, that Daniella discovered in her research, are a type of interneuron, which adjust and balance signals between the cells in the brain. This little parvalbumin can be likened to a conductor who makes sure that everyone is coordinated, that the flow of information takes place at the right pace. Without a conductor, that is if the parvalbumin cells are damaged or dead, the timing goes wrong and signals end up out of sync. There is much evidence pointing to this possibly being one of the causes of such diseases as epilepsy, schizophrenia and Alzheimer's. When comparing the brain of a healthy mouse and one with Alzheimer's, one can clearly see that the parvalbumin interneurons are fewer in the diseased brain. And when the brain loses nerve cells, it cannot regenerate new, healthy ones, like skin cells when we get injured. Instead, the body needs help from an external source. And this is where Daniella's research comes in. The work is moving quickly forward. They have now succeeded in reprogramming human glial cells become parvalbumin. With this electrode, you can record the function of the neuron, so you can see how the neuron is working. And this is a key property for the parvalbumin interneuron, because they are so important for the signaling and the function in the brain. Here we have a very nice firing of this. This is not really fast spiking, but it's still quite a lot of action potentials. Ongoing studies are now trying to put these interneurons into the mouse brain and see if the neurons can survive and function and also make contact with the other surrounding neurons. If the reprogrammed cells successfully establish themselves and start signaling in the mouse's brain, Daniella will be one step closer to treat patients. This might not lead to a therapy within the coming years, but the research field is advancing very fast. In the future, doctors will hopefully be able to program glial cells in the brain to replace broken or dead parvalbumin interneurons. And in this way, treat patients with these neurological diseases. All thanks to an experiment that didn't go as planned and ended up so much better than anyone could have imagined.