Does the brain produce neurons throughout life and if so why? Some answers with Nathalie Corré-Polleau, a researcher at the National Center for Scientific Research (CNRS).
The image above shows neurons in the olfactory bulb region in a young mouse brain slice. Different colors allow us to better understand the development of neurons in the mouse brain after birth.
The concomitant presence of green fluorescence and red or orange fluorescence in the cell makes it possible to determine whether the newly formed neuron (in green) is a dopamine (red) or a calretinin (orange) neuron. Blue indicates only the nuclei of all cells present in the image.
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Does the brain produce neurons throughout life and why?
Until the middle of the 20th centuryE century, one of the main tenets of neuroscience is that neurons are produced before birth, during the development of the nervous system. Since then, an adult’s brain may lose some as it ages. However, in the 1990s, this dogma was overturned by studies proving the existence of stem cells in the brains of many organisms such as birds, fish and mammals.
Stem cells are “mother” cells capable of giving rise to all cell types in an organism. They can remain into adulthood in different tissues or organs before finally differentiating, that is, forming cells specialized for the organ in question—in this case, the brain.
It is now well established that specific types of neurons continue to be generated from these stem cells throughout life. In mammals, two specific regions are affected by a constant supply of new neurons: the hippocampus, the seat of memory control and learning, and the olfactory bulb, which is needed to decode olfactory sensory information from the environment. out.
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Key role of genes
This cellular renewal will allow adaptation (or “plasticity”) of neuronal circuits to new information. What’s more, stem cells will also form a cellular reservoir capable of reactivation in a pathological context during brain injury, to precisely redirect the production of neural cells (neurons and glia) to the damaged region.
Behind the general term neuron hides in fact a wide variety of cell types with different morphologies and functions. One of the puzzles of neurogenesis is therefore to understand how similar-looking stem cells can generate such a diversity of neurons. Genes play an important role in this process and therefore it is important to determine which genes are required to produce one neuronal type rather than another.
This knowledge is particularly crucial for developing therapeutic approaches in which stem cells will be forced to deviate from their normal function to force them to replace neurons altered by pathology, for example in the case of neurodegenerative disease.
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How to identify the function of a gene in the formation of neurons?
By altering the activity of this gene in stem cells, either eliminating it or increasing it, and observing the effect of the change on the fate of the stem cells: what types of neurons are they able to produce?
In mice, it is possible to directly and precisely insert a gene or molecule that inactivates this gene into specific brain stem cells of living animals, which give rise to the neurons of the olfactory bulb. And to be able to identify cells modified in this way, in the case of this image “GFP” (green), the gene coding for the fluorescent protein is simultaneously represented in the same cells. It is then sufficient to follow the fate of green cells in the olfactory bulb and identify the type of new neurons.
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For this study, the tissue was treated with two fluorescent antibodies (red and orange) to reveal the presence of specific proteins in the cells, each antibody interacting with a specific protein. The red and orange cells respectively correspond to the two subtypes of neurons present in the olfactory bulb: dopamine neurons (neuromediators) and calretinin neurons (calcium-binding proteins). Green cells correspond to new neurons produced on the first day after birth from modified stem cells, into which the fluorescent protein GFP has been introduced by genetic manipulation. Green and orange neurons indicate that this new neuron is a calretinin neuron, and green and red neurons are dopamine neurons.
The original version of this article was published in conversation.
