In The Spotlight
We read an interesting paper! Here is what it says…about Adult Hippocampal Neurogenesis.
Written by Chiara
One month ago, Nature published the latest paper from the lab of Arturo Alvarez-Buylla, one of the most eminent scientists in the field of adult neurogenesis. In this work entitled Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults, Sorrels & Paredes and colleagues report their investigation on the possibility of producing newborn neurons in humans after birth.
Several studies have challenged the dogma of the lack of adult human neurogenesis in adulthood, by means of different techniques. Most notably, a study from Spalding & Bergman and colleagues from 2013 detected the levels of post-atomic-bomb-test-derived 14C in genomic DNA of hippocampal neuronal cells to determine whether they had been produced after birth. Their research led to the conclusion that about 700 new neurons are produced each day in the human hippocampus! This was in clear contrast to the previous reports of a sharp decline of the production of neurons after childhood.
In this new exciting paper, Sorrels, Paredes and colleagues analysed different tissue samples from subjects spanning the ages of 14 gestational weeks to 77 years. The immunohistochemical analyses determined that, contrary to what happens in rodents, humans do not have a subgranular zone (SGZ), the thin layer of cells where adult neural stem cells reside and adult neurogenesis occurs. Our dentate gyrus (DG) seems in fact, to not harbor many proliferating (Ki67-positive or Sox2-positive) cells. By the first year of life, their number is reduced to few, sparse cells present around the hilus.
The reduction in the number of proliferating progenitors is accompanied by a reduction in the number of newborn neurons, detected by the markers doublecortin (DCX) and PSA-NCAM. Very few cells are present in the DG of a 1-year old subject and the number drops to an average of 12 cells/mm2 in tissue from a 7 year old child. Interestingly, a similar decay was found when analysing the DG from individuals of the species M. mulatta (rhesus macaque), despite the fact that they have a postnatal SGZ. Normalising the developmental stages of macaques with the developmental stages of humans shows the same result: the production of newborn neurons drastically drops after birth, and eventually becomes very rare after childhood.
These results suggest that humans generate very rare newborn neurons in the hippocampus, with a neurogenic outcome similar to the one obtained by former immunohistochemical studies. While such studies identified newborn neurons almost exclusively by their DCX expression, it is important to note that Sorrels, Paredes and colleagues determined that DCX alone could lead to an error in the estimate due to the fact that even some glial cells – namely microglia and oligodendroglia can express it. In fact, they coupled DCX to PSA-NCAM, a neuronal lineage marker, in order to define newborn neurons. Moreover, by electron microscopy imaging, they show how such cells mature and undergo morphological changes through different life-stages.
Despite the fact that, due to the limited number of samples analysed, this study doesn’t take into account inter-individual variations, it does confirm previous studies using a more thorough and solid experimental setup.
Do we produce new hippocampal neurons throughout our lives? Do we need them at all? Further investigations will definitely reveal a clearer picture. The fact that we do not generate huge number of neuronal progeny after birth shouldn’t be seen as a problem, though. Numerous mammals have indeed so far been found to lack adult hippocampal neurogenesis, which might hint at a different mechanism for processing hippocampal information throughout life.
Written by Chiara Galante; Edited by Radhika Menon. Featured image: confocal picture of mouse adult hippocampus with DCX-positive newborn neurons, courtesy of Chiara Galante (acquired at the Microscopy facility/IMB Mainz).