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3 mins read
Researchers at the Karolinska Institutet identified immature neurons and active stem cells in the hippocampus of adult individuals, resolving a decades-long scientific controversy. Thanks to new genetic analysis techniques and computational modeling, the study provides solid evidence that the human brain maintains its regenerative capacity, opening new possibilities for treating neurodegenerative diseases and mental disorders.
Since the 1960s, the scientific community has debated whether the adult human brain is capable of generating new neurons. Although this phenomenon—known as neurogenesis—had been demonstrated in adult brains of other species such as mice, studies in humans failed to provide conclusive evidence. Most of the data were circumstantial or contradictory, partly due to technical challenges in studying the human brain with the same precision as in animal models. However, a new study published in the journal Science appears to finally settle this controversy.
The study, led by Jonas Frisén and a team of researchers from the Karolinska Institutet in Sweden, combined advanced molecular biology techniques and computational analysis to identify both immature neurons and their precursor cells in human brains ranging from infancy to 78 years of age. This finding provides the first solid evidence that the full process of neurogenesis—from stem cells to newly born neurons—remains active throughout life in the human hippocampus.
The key to the study was the use of single-nucleus RNA sequencing, a technique that allows researchers to analyze the genetic activity of individual cell nuclei. The team isolated over 100,000 nuclei from hippocampal tissue of children aged 0 to 5, and more than 200,000 from adolescents and adults aged 13 to 78. Thanks to these RNA sequences, they were able to identify molecular markers that define neural stem cells and immature neurons.
Unlike previous studies that relied on unreliable or poorly adapted markers from animal models, this approach provided a more robust and detailed profile of cells at different stages of neuronal development. The team also used machine learning algorithms trained on data from infant brains to detect the same cellular signatures in adult brains. This strategy enabled the identification not only of neural progenitor cells but also of a continuous neurogenic process over time. These cells were located in the dentate gyrus of the hippocampus, a subregion involved in memory, learning, and cognitive flexibility. Additional tools such as RNAscope and Xenium helped pinpoint the spatial location of these cells in brain tissue.
Although adult neurogenesis was confirmed, researchers also observed significant variability among individuals. In a sample of 14 adults, two showed a high number of precursor cells and immature neurons, while five showed no clear evidence of neurogenesis. These differences have not yet been definitively attributed to biological or technical causes, but they raise important questions about the factors that influence each brain’s ability to generate new neurons. For example, one adult with a high presence of precursor cells had lived with epilepsy. In animal models, increased neurogenic activity has been associated with epileptic seizures, although this relationship remains uncertain in humans.
The study also confirms that human neuronal progenitors share similarities with those observed in species such as mice, pigs, and monkeys, though with some differences in the genes activated during the process. It also refutes one of the most persistent hypotheses in the field: that immature neurons found in adults were merely remnants from early development, stored since childhood. Instead, the data show that these neurons are continuously generated from precursor cells that actively divide in adulthood.
Until now, one of the main obstacles to demonstrating adult neurogenesis in humans was the scarcity of precursor cells compared to other neuronal populations, making them difficult to detect. Moreover, molecular markers used in previous studies did not translate well from animal models to humans. The integration of transcriptomics (the study of the complete set of RNA molecules, or transcriptome, present in a cell or tissue at a specific time), spatial analysis, and computational modeling finally overcame these barriers.
Beyond settling a long-standing scientific controversy, these findings could have significant clinical implications. Since many neurological and psychiatric disorders—such as Alzheimer’s and depression—affect neuronal viability, understanding how neurogenesis occurs in humans could open new avenues for developing regenerative therapies. Stimulating this process in a controlled way could become a future strategy to restore brain functions impaired by age or disease. This provides a fundamental piece for understanding how the human brain works and changes throughout life. The question of whether the adult brain generates new neurons now seems finally resolved. Science can now focus on understanding how these neurons contribute to brain function and what conditions modulate their production.
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