Research conducted at the Joint Center Neuroscience Institute (IN) of the Advanced Scientific Research Council (CISC) and Miguel Hernández University (UMH) in Elche has shown for the first time that it is possible to obtain specific neurons. A specific brain area derived from astrocytes, a type of astrocyte in the nervous system, which plays a very important role in the function of the brain. This study in rodents has been published in the journal “Science Advances”.
These astrocytes have been reprogrammed with a major gene called Neurogenin2, which has reached its destination in the mouse brain from the hands of the virus. The researchers also observed how they express the genes of their sister neurons (from a common progenitor cell) in each specific brain region, which makes it possible to reprogram them into specific types of sensory neurons.
The classic genes of neurons are also expressed by astrocytes. Astrocytes and neurons share the code for each brain region. This is important because it provides the possibility to restore lost neural circuits in congenital blindness or deafness in the future.
Guillemina Lopez Bendito
“We found that the classic genes in neurons are also expressed by astrocytes, albeit at a lower level. Astrocytes and neurons and possibly other nerve cells share the code for each brain region. This is very important, Because it opens up the possibility of restoring lost neural circuits in congenital deafness or blindness in the future.
Restore lost senses
The two brain structures involved in this process are the thalamus and the cerebral cortex. The thalamus receives information from the outside and the cerebral cortex processes it. When the uptake of sensory stimuli decreases, some neurons and circuits in these two areas of the brain are lost or greatly reduced.
Astrocytes may be the key to recovering those lost circuits. Until recently, these glial cells were still considered “secondary roles” in the brain and spinal cord, and their role was to provide nutrients and structural support for neurons.
However, the function of astrocytes goes even further: they also participate in tasks previously thought to be exclusive to neurons, such as information processing, transmission, and storage. The ability to transform into neurons after induction further proves their important role.
Another finding of this work is that cells produced in specific areas of the brain, whether neurons or other types of nerve cells, have molecular characteristics. It is the specific gene expression in each region shared with neurons that gives astrocytes the ability to become specific types of neurons under certain conditions.
Astrocytes may be the key to recovering those lost circuits. Until recently, these glial cells were considered “secondary roles” in the brain and spinal cord, and their role was to provide food and structural support for neurons.
“Now, we are trying to find out whether astrocytes can spontaneously become neurons under certain conditions. For example, when we cause an increase in reactive astrocytes,” López-Bendito explained. Reactive astrocytes are responsible for protecting neurons when damage occurs, although sometimes their action can damage them if their response is very strong.
The increase in reactive astrocytes or astrocytosis makes these cells more malleable or compliant. “In this case, we believe that without introducing a major gene to guide reprogramming, we can spontaneously observe the ability of astrocytes to become neurons,” Lopez Bendito said.
“The process of reprogramming astrocytes into neurons is feasible. We have achieved this goal in in vivo and in vitro studies in control mice. Now, our immediate challenge is to make congenital blind mice models It is possible. The researchers concluded: “We will use the same technology to reprogram sensory astrocytes and turn them into visual neurons to replace those lost neurons. “
Herrero-Navarro et al. Astrocytes and neurons share regional-specific transcriptional features, giving neurons reprogramming with regional identity.Scientific progress
This project was funded by Generalitat Valenciana (Generalitat Valenciana) of 400,000 euros. It is the seed of a new project initiated by the La Caixa Foundation through the CaixaResearch Health Research Call. The amount is 499,000 euros.