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The brain regenerates even as adults: a 'reservoir' of new neurons discovered

Thanks to artificial intelligence and cutting-edge techniques, researchers have finally dispelled a decades-old doubt: the human brain retains the capacity for neurogenesis well into old age

by Health Review

3' min read

3' min read

For decades, it was taken for granted that, once the human brain reached adulthood, it could no longer produce new neurons. Now, a team at Karolinska Institutet led by Jonas Frisén challenges this dogma with solid data. Using single-core RNA sequencing and an artificial intelligence algorithm, the researchers have shown that progenitor cells and immature neurons exist in the hippocampus from early infancy to 78 years of age. The discovery, published in Science, opens up new avenues for understanding memory, mood and potential regenerative therapies in neurodegenerative and psychiatric diseases.

This new neuronal growth, also called neurogenesis, takes place in the dentate gyrus of the hippocampus, a fundamental part of the brain involved in learning, memory and emotions. It is here that incoming information from the cortex is processed, transformed into mnemonic traces.

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Demolishing a decades-old dogma

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Since the 1960s, however, a growing number of studies in animal models have shown not only that in adults the hippocampus continues to generate new neurons, but also that these newly born cells actively integrate into existing circuits, influencing memory, learning and emotional regulation. In humans, this dogma has been harder to shake, as contradictory evidence has fuelled a decades-long controversy over the existence and mode of formation of new neurons in the adult human brain.

The differences between the human studies stem essentially from three technical variables: the time between the death and preservation of the tissue can alter its structure; the molecular markers used to mark the cells are not always the same and bind with different efficiencies; and the methods for extracting the RNA, which reveals which genes are active, have variable sensitivity, so that some protocols detect many more signals than others. These discrepancies can make us lose sight of progenitor cells, which are very rare, or confuse them with the more common support cells of the brain, thus leading to apparently contradictory results.

'We used transcriptomics, i.e. the analysis of all the RNAs produced by a cell at a given time, to understand which genes are active, and artificial intelligence to show that neural progenitor cells and their successors, the immature new-born neurons, are present from infancy to old age in humans,' comments Marta Paterlini, who participated in the study.

Frisén and his team studied almost half a million nuclei from the human hippocampus to check the persistence of neurogenesis: starting from the nuclei of children (0-5 years old) they identified markers of neural progenitors and immature neurons, then applied a machine learning algorithm trained on these data to the nuclei of adults (13-78 years old), recognising the same molecular signatures; finally, they showed that the adult brain retains, with some variability between individuals, a small reservoir of cells capable of generating new neurons.

The researchers also used a technology called Xenium, which allows them to mark and visualise up to 300 different markers within each cell. Thanks to these markers, they were able to precisely locate the neuronal progenitors in the hippocampus and verify that they did not express the hallmarks of other cell types, such as microglia or astrocytes. This unequivocally confirms that these are true precursors destined to become neurons. With these results, the dogma of a static adult brain gives way to a new horizon of plasticity and regeneration.

The revolutionary perspectives of neurogenesis

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The challenge now is to understand why and how neurogenesis occurs in humans. "Neurogenesis in adults offers hope for brain repair. When trauma or disease damages neural circuits, the ability to generate new neurons opens up the prospect of natural regeneration, replacing lost cells or restoring broken pathways. Studies in rodents show that lifestyle factors such as exercise, enriched environments, and certain drugs (antidepressants) can increase the rate of new cell production in animal models, suggesting that we could harness this process to support resilience against age-related decline or mood disorders,' Paterlini comments.

Although precise therapeutic strategies for humans are still the subject of research, the mere fact that our adult brain can generate new neurons radically changes the way we view lifelong learning, recovery from injury and the untapped potential of neuronal plasticity.

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