To the Editors:
How do Shawn Sorrells, Arturo Alvarez-Buylla, and Mercedes Paredes (“No Evidence for New Adult Neurons,” May–June, Perspective), explain the contradictory findings recently published in the journal Cell Stem Cell in which another group of researchers argued that neurogenesis occurs in the human hippocampus across the life span? Are the methods employed by Sorrells and his coauthors better than those used by the authors of the paper in Cell Stem Cell? Is there still some doubt about the findings?
Henry A. Buchtel
University of Michigan
Ann Arbor, MI
Drs. Sorrells, Alvarez-Buylla, and Paredes respond:
Although the new study in Cell Stem Cell by Maura Boldrini and her colleagues offers interesting evidence of declining blood vessel growth in the adult hippocampus, we dispute the interpretation of their cellular staining experiments as evidence of new neurons in the adult brain.
Identifying new neurons is technically challenging—in our recent study we made similar observations to those reported by Boldrini and her colleagues. After performing extensive additional analyses, including evaluating the shape and appearance of the cells in question with light and electron microscopy and studying gene expression patterns, we determined that these cells were not young neurons or neural progenitors but rather were different types of cells altogether, such as nonneuronal glial cells.
For now, we do not think this new study challenges what we have concluded from our recently published observations: If neurogenesis continues in the adult human hippocampus, it is an extremely rare phenomenon.
In our view, the new study’s exclusive reliance on labeling cellular proteins associated with new neurons is not sufficient evidence to conclude that the cells observed are new neurons. Based on the representative images the authors present, the cells they deem as new neurons in the adult hippocampus are very different in shape and appearance from what would be considered a young neuron in other species or what we have observed in young children.
We also have technical concerns about some of the key protein labeling performed in this study. Based on the images presented in the paper, some of these labels appear to be nonspecific (for example, markers of glial cells and dividing cells appear to label large, fully mature neurons), further calling into question the results overall.
We also question the assertion by Boldrini and her coauthors that the subgranular zone (SGZ), the key site of adult neurogenesis in the rodent brain, is present in their adult human brain samples. None of their histology shows this layer of small, frequently proliferating cells, and their blood vessel staining fails to show the dense plexus of blood vessels that characterizes the SGZ in rodents.
Given the unclear nature of the cells presented, the lack of a clear SGZ, and the developmental trajectory that we describe in our study, with new neurons clearly present in children but not in adults, we think that the simplest interpretation is that neurogenesis in the adult human dentate gyrus is absent or extremely rare. It boils down to interpretation of equivocal cells, which we took extra steps to characterize and which we found were not new neurons as they first appeared.