New neurons detected forming in adult human brains

This work corroborates the results obtained previously in the so-called “bomb study”. It took advantage of the radioactivity incorporated into the environment slightly contaminated by experimental nuclear explosions carried out in the Nevada desert (United States) to demonstrate that, in the hippocampus, specifically in the dentate gyrus, there was postnatal neuronal proliferation. The result broke the dogma that there was no appreciable neuronal enrichment after birth.

This work denies the existence of a time barrier beyond which our brain cannot induce the proliferation of neurons. Even Ramón y Cajal firmly believed in this dogma, which stated that we were all born with a number of neurons that could only decrease, but never increase after birth.

However, this study indicates that, at least until the age of 78, our brain is capable of replacing neurons in order to maintain the most important function of our hippocampus, namely memory. This fact, coupled with the fact that the hippocampus is of particular interest because of its leading role in Alzheimer's disease, highlights the scale and importance of these discoveries.

The article contributes significantly to knowledge about the process of adult hippocampal neurogenesis in humans. It has used sophisticated methodologies that provide unprecedented spatial resolution in this field and has helped identify a special type of cell, proliferative stem cells, using transcriptomic techniques.

The study uses two novel techniques, called single-nucleus RNA sequencing (snRNA-seq) and single-cell resolution spatial transcriptomics, together with machine learning. The application of these methodologies has allowed the identification of proliferative progenitor cells in the human hippocampus. These cells are very rare and very similar to glial cells, so the application of these techniques has been key to identifying them, something that previous studies had not been able to do.

[Regarding possible limitations] Any research based on the study of post mortem human samples has certain inherent technical limitations, but this study is a tour de force in the field.

The work presented here comes from Jonas Frisén's research group. This group is a leader in the study of hippocampal development and, in particular, neurogenesis in the brain. The author of the paper is Ionut Dumitru, a postdoctoral researcher whose publications always focus on neurogenesis in adults. The study is very good because of its use of cutting-edge technologies, such as artificial intelligence and single-cell RNA sequencing databases. In addition, multiplex platforms were used to determine the exact position of each cell studied within the tissue.

The authors had already been studying neurogenesis in adults for years, both in laboratory animals and in the human brain. In fact, they had already published the existence of stem cells in both animals and humans.

There are several regions in the brain with neurogenic capacity in adults. These areas, which were first discovered in animals, include the subventricular zone (Alvarez-Buylla et al., 2000) and the hippocampus (Cameron & McKay, 2001). The subventricular zone is a region that lines the lateral ventricles, where the ependymal cells, which produce cerebrospinal fluid, are also located. The other region with neurogenic activity in adults is found in the hippocampus, in a very specific area called the dentate gyrus. Animal experiments have shown that the subventricular zone gives rise to a type of neuron called interneurons that migrate rostral to the olfactory bulbs for cell replacement. Today, it is even known that each subdivision of this region gives rise to a specific type of interneuron. Recent studies from Dr Alvarez Buylla's laboratory have shown that this migration and neuronal replacement also occurs in humans, but unlike rodents, where it occurs throughout their lives, in humans it only occurs up to the age of two (Paredes et al., 2016). The other neuron-producing niche, as we have said, is located in a region of the hippocampus called the dentate gyrus. The hippocampus is a region of the brain that is heavily involved in memory and learning. In addition, it has been found to be one of the first regions affected in various neurological and neurodegenerative diseases such as Alzheimer's and Parkinson's. In fact, it is known that in Alzheimer's there is an alteration of the populations of stem cells and immature neurons in this area (Terreros-Roncal et al., 2021).

Although many studies confirm the existence of stem cell populations in the dentate gyrus in both animals and humans, until now there had always been the possibility that this was not the case. This study by Jonas's laboratory puts an end to this doubt. The group behind the study conducted a bioinformatic analysis of the genetic profile of the cells that make up the dentate gyrus, confirming the existence of progenitor cells in humans at both juvenile and adult stages. To do this, they first analysed and characterised the cells of the dentate gyrus in rodents (where the existence of stem cells has been proven). With this information, they trained the AI to distinguish between stem cells or immature progenitor cells and adult neurons. Once they verified that the system was able to distinguish all cell types, they fed it data from adult brains. The AI verified the existence, albeit scarce, of cells with the capacity for division in the dentate gyrus, corroborating what other authors had already pointed out.