This week I’m re-visiting adult human neurogenesis: the seminal neuroscience finding that new neuronal cells are born in adult human brains after the normal developmental period in which neurons are generated. This remarkable discovery was made by Peter Eriksson and colleagues in the lab of Fred Gage at The Salk Institute for Biological Studies. Prior consensus in the field was that once neurons died (a hallmark of neurodegenerative diseases such as Alzheimer’s and Parkinson’s) there was no regeneration of neurons. The view was that brains generated a finite number of neurons for the life of the organism, and these neurons networked to handle all learning of new knowledge and the making of new memories and associations—quite an incredible feat! However, the Gage group questioned the current model and found that there was neurogenesis in specific areas of rodent brains, a huge finding in and of itself. But this generated some controversy-- another group published that neurogenesis was not taking place in marmosets (a higher mammal than rodents) and therefore it was likely not happening in other primates, i.e., humans. Therefore, the publication of “Neurogenesis in the Adult Human Hippocampus” in Nature (Eriksson et al., 1998) helped to resolve what had become a contentious issue and definitively showed that indeed, new neurons are being born and incorporated into the hippocampal region of adult brains.
Interestingly, this research was only possible because of the drug BrdU, which is commonly used in cancer patients for diagnostic purposes. Because BrdU is a thymidine analog (one of the four nucleotides that make up our DNA), the drug incorporates into replicating DNA. Replicating DNA is a sure sign of a dividing, or proliferating, cell. Scientists can go into a piece of tissue and use a technique called immunohistochemistry to locate the cells in which BrdU has incorporated into the DNA. This method essentially provides a snapshot of which cells were newly generated at a specific point in time (the point at which BrdU was introduced). Looking in the postmortem brain tissue of the BrdU injected cancer patients aged 58 years and older, Eriksson and colleagues found BrdU positive cells within the brain, and found these cells up to 781 days post injection. The morphological appearance of these cells, their localization to specific areas of the brain tissue, and the fact that they expressed salient neuronal markers indicated that these cells were not an isolated population of replicating cells, but were indeed neurons that incorporated into the hippocampus, the region of the brain most intimately involved in learning and memory.
The observation that neurogenesis occurs within the human hippocampus throughout life teaches us two lessons. The first, is that the brain is more plastic than earlier dogma had us believe, and an entire neuroscience field of how and where new neurons become incorporated into existing circuitry has made interesting discoveries since 1998. Ideally, neuroscientists will be able to gain insight into how we may aid in the generation of new neurons in disease states. The second lesson we can take from this story is that there indeed is a place in science for rigor and for re-examination of the status quo, which may lead us to incredible new findings.
Eriksson, P.S., Perfilieva, E., Bjork-Eriksson, T., Alborn, A.M., Nordborg, C., Peterson, D.A., and Gage, F.H. (1998). Neurogenesis in the adult human hippocampus. Nat Med 4, 1313-1317.