The long-standing debate over whether the adult human brain continues to produce new neurons has taken a significant turn. A study from researchers at Karolinska Institutet, Sweden, confirms that neurogenesis persists throughout life in the hippocampus – a region crucial for memory and learning. The findings offer the most comprehensive evidence to date of ongoing neuronal formation in adult brains and provide tools for tracking its cellular origins.
The study focused on identifying neural progenitor cells, the precursors to mature neurons, which have remained elusive in human tissue. “We have now been able to identify these cells of origin, which confirms that there is an ongoing formation of neurons in the hippocampus of the adult brain,” said Jonas Frisén, senior author and professor of stem cell research at Karolinska, in a press release.
To trace the full developmental path of new neurons, the team examined post-mortem hippocampal tissue from 35 individuals aged 0 to 78 years. Using single-nucleus RNA sequencing (snRNA-seq), they profiled transcriptional activity in individual cells, identifying a continuum from quiescent stem cells through proliferating progenitors to immature neurons.
These findings were validated through flow cytometry, which quantified the abundance of cells at each stage, and spatial transcriptomic techniques, including RNAscope and Xenium In Situ, to localize gene expression within the dentate gyrus – a subregion of the hippocampus known to support neurogenesis. Across all ages, the authors detected active mitotic cells expressing hallmark genes such as MKI67 and DCX, consistent with ongoing neuronal development.
While the study confirmed consistent presence of neural progenitors into old age, it also highlighted individual variability. Some adults retained a high number of progenitor cells, while others showed few, suggesting biological and perhaps environmental factors influence adult neurogenesis.
Interestingly, the developmental trajectory of these human hippocampal neurons closely resembled that seen in mice, pigs, and nonhuman primates, though with notable differences in gene activity. The discovery that human adult brains retain neurogenic potential raises new possibilities for treating cognitive decline and psychiatric conditions.
“Our research may also have implications for the development of regenerative treatments that stimulate neurogenesis in neurodegenerative and psychiatric disorders,” Frisén said.
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