Transform astrocytes into neurons for the first time to repair visual circuits

Research carried out at the Institute of Neurosciences (IN), a joint center of the Higher Council for Scientific Research (CISC) and the Miguel Hernández University in Elche (UMH), has shown for the first time that it is possible to obtain specific neurons from a specific brain region made from astrocytes, a type of star-shaped cells of the nervous system that carry out very important functions for the functioning of the brain. The study, conducted in rodents, has been published in the journal Science Advances.

These astrocytes have been reprogrammed by a master gene, called Neurogenin2, which reaches its destination in the brain of mice from the hand of a virus. Researchers have also observed how they express genes of their sister neurons (coming from a common progenitor cell) in each specific brain region, which has made it possible to reprogram them in a specific type of sensory neuron.

Classic genes of neurons are also expressed by astrocytes. And there is a code of each brain region that astrocytes and neurons share. This is important because it opens the possibility of recovering lost neural circuits in the future in the congenitally blind or deaf.

Guillermina López-Bendito

“We have discovered that classical genes in neurons are also expressed by astrocytes, albeit at a lower level. And that there is a code of each brain region that is shared by astrocytes and neurons, and probably other nerve cells as well. This is important because it opens up the possibility of recovering lost neural circuits in the future in the congenitally deaf or blind ”, explains Guillermina López-Bendito, director of the Developmental Neurobiology Unit of the Institute of Neurosciences, who has led the research.

Restore lost senses

The two brain structures involved in this process are the thalamus, which receives information from outside, and the cerebral cortex, which processes it. When there is a loss in the uptake of sensory stimuli, part of the neurons and the circuits of these two regions of the brain are lost or considerably reduced.

Astrocytes could be crucial in restoring those lost circuits. Until recently, these glial cells were considered ‘secondary actresses’ in the brain and spinal cord whose role was to provide nourishment and structural support to neurons.

However, the function of astrocytes goes further: they also participate in tasks that were previously believed exclusive to neurons, such as information processing, transfer and storage. The ability to transform into neurons after induction is further proof of their important role.

Spontaneous repair

Another finding of this work is that the cells that are generated in a specific area of ​​the brain, be they neurons or other types of nerve cells, share a molecular signature. It is precisely the specific gene expression of each region shared with neurons that gives astrocytes the ability to become neurons of a specific type under certain conditions.

Astrocytes could be crucial in restoring those lost circuits. Until recently, these glial cells were considered ‘secondary actresses’ in the brain and spinal cord whose role was to provide nourishment and structural support to neurons.

“Now we are trying to find out if, spontaneously, astrocytes can become neurons in specific situations. For example, when we cause an increase in reactive astrocytes ”, explains López-Bendito. Reactive astrocytes are responsible for protecting neurons when damage occurs, although sometimes their action can also harm them if their reaction is very powerful.

The increase in the number of reactive astrocytes, or astrogliosis, favors these cells to become more malleable or more docile. “In these circumstances, we think that, without the need to introduce a master gene to guide reprogramming, we could spontaneously observe the ability of astrocytes to become neurons,” says López-Bendito.

“The process of reprogramming astrocytes to neurons is feasible. And we have achieved this in both in vitro and in vivo studies in control mice. Now our immediate challenge is to make it possible in congenitally blind mouse models. We will use this same technique to reprogram sensory astrocytes and turn them into visual neurons that replace those that had been lost ”, concludes the researcher.

Reference:

Herrero-Navarro et al. ‘Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming’. Science Advances

This project has been financed by the Generalitat Valenciana with 400,000 euros and is the seed for a new project promoted by the La Caixa Foundation with 499,000 euros, through the CaixaResearch Call for Health Research.

Source: IN-CSIC-UMH / CSIC

Rights: Creative Commons.