When I was a child, my grandma used to tell me that I shouldn’t hit my head when playing because I would kill my neurons and, she would add, we are born with all the neurons that we need. No more neurons are produced as we get older.
Fifteen years later, in my introductory neuroscience course, we learned about the concept of neurogenesis. Neurogenesis is the process of generating new neurons. We learned about the research that challenged the major dogma in neuroscience: no new neurons are produced in the adult brain. This dogma was held by three main factors:
- Clinical evidence: adult patients suffering from brain injury do not easily recover.
- Networks: how can newborn neurons integrate into the already existing networks of the brain? How can neurons integrate without disturbing the already established information in our brain?
- Stem-cells: the importance of pluripotent cells (cells that can differentiate into many other types of cells) had not been recognized yet.
Fernando Nottebohm, an Argentinian neuroscientist working at Rockefeller University, is considered as the first one who provided definitive evidence that there are newborn neurons in the adult vertebrate brain. Since then, scientists have used similar methods to study neurogenesis. The basic principle is that, because all cells come from other cells and any cell going through division needs to make a copy of its DNA, we can use an analog of thymidine to identify newborn cells. You can think of thymidine as a lego piece that is incorporated into the DNA of replicating cells. Cells can’t differentiate between real thymidine and thymidine analogs (e.g., BrdU), so they incorporate this thymidine analog, which we can later visualize using antibodies. An important note is that BrdU and any other thymidine analogs allow us to make conclusions about newborn cells, but they do not say anything about the type of cell they are.
In order to identify newborn neurons, scientists add a second type of labeling for neural markers. Mature neurons express proteins that make them neurons instead of, for example, skin cells or glial cells (also found in the brain). Some of these markers are NeuN and calbindin. Therefore, if we find neurons in brain tissue labeled for both BrdU and a neural marker, we can conclude that these are newborn neurons!
Neurogenesis in the adult human hippocampus was first reported by Eriksson and colleagues back in 1998. In their experiment, they studied brain samples from patients who died from cancer and who were previously injected with BrdU (to keep track of their tumor growth). They found newborn cells that expressed neural markers in the hippocampus, a brain region involved in learning and memory.
Last week, however, Sorrells and colleagues reported that “Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults”. In the NPR, they released a podcast called “Sorry, Adults, No New Neurons For Your Aging Brains”. Apparently, we are back to adopting my grandma’s thinking, but after reading the paper, I ended up believing Professor Beltz’s explanation. She studies neurogenesis in crayfish and they discovered that the immune system provides the neural precursors needed to have neurogenesis. In Sorells and colleagues’ paper, they were actually looking at the neural precursors, not at the newborn neurons (at least in the experiment with humans). They couldn’t find a “defined population of progenitor cells […] in the subgranular zone [a region in the hippocampus] during human fetal or postnatal development”. Therefore, they concluded that neurogenesis is not happening in the adult brain because there are not neural precursors in the brain.
However, as Professor Beltz proposes, there might be an extrinsic source of neural precursors: the immune system. Some experiments studying women who received a bone marrow transplant from men support this hypothesis because Y-chromosome-containing neurons were found in their brain! Of course, there are people who think that these results might come from a problem with a leaky brain blood barrier of patients (the brain blood barrier protects the brain and does not let in many extrinsic cells/molecules). Others believe that the neural proteins found in these cells are the product of fusion instead of being produced by transdifferentiation (going from a type of cell to another one). Transdifferentiation is a conflictive idea because neural tissue emerges from a type of tissue (ectoderm) that is different from the tissue that produces cells from the immune system (mesoderm).
I am starting to get very technical and it’s 1:28 am, so I just want to finish this by saying that we might still live in dogma. There are tons of papers out there showing that neurogenesis occurs and that we might be looking at the wrong place looking for the wrong thing because we won’t change the dogma in science. Cells from the immune system might be the precursors of neurons in our brain!