Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults

• Published in: Nature (London) 2018-03, Vol.555 (7696), p.377-381
• Main Authors: Sorrells, Shawn F., Paredes, Mercedes F., Cebrian-Silla, Arantxa, Sandoval, Kadellyn, Qi, Dashi, Kelley, Kevin W., James, David, Mayer, Simone, Chang, Julia, Auguste, Kurtis I., Chang, Edward F., Gutierrez, Antonio J., Kriegstein, Arnold R., Mathern, Gary W., Oldham, Michael C., Huang, Eric J., Garcia-Verdugo, Jose Manuel, Yang, Zhengang, Alvarez-Buylla, Arturo
• Format: Article
• Language: English
• Subjects: 13; 14/1; 14/19; 14/28; 14/32; 14/63; 38/5; 38/61; 631/136/368/2431; 631/378/368/2431; 64; Adolescent; Adult; Adults; Age; Aged; Animals; Animals, Newborn; Brain research; Cell Count; Cell Proliferation; Cells (biology); Child; Child, Preschool; Children; Coalescing; Dentate gyrus; Dentate Gyrus - cytology; Dentate Gyrus - embryology; Epilepsy; Epilepsy - pathology; Female; Fetal Development; Fetuses; Healthy Volunteers; Hippocampus; Hippocampus (Brain); Hippocampus - anatomy & histology; Hippocampus - cytology; Hippocampus - embryology; Humanities and Social Sciences; Humans; Infant; Learning; letter; Macaca mulatta; Male; Memory; Microscopy; Middle Aged; Morphology; multidisciplinary; Neural Stem Cells - cytology; Neurogenesis; Neurons; Neurons - cytology; Observations; Patients; Physiological aspects; Progenitor cells; Rhesus monkey; Science; Stem cells; Young Adult
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature25975

Recruitment of young neurons to the hippocampus decreases rapidly during the first years of life, and neurogenesis does not continue, or is extremely rare, in the adult human brain. No new neurons in adult humans Previous lines of evidence have suggested that neural precursors are present in adult humans and continue to generate new neurons in the hippocampus even after full maturation. Here, Arturo Alvarez-Buylla and colleagues re-visit that concept and come to a different conclusion. Using a more comprehensive and larger set of samples of human hippocampus than those analysed in previous studies, the authors find evidence for the production of new neurons early in life, but note that hippocampal neurogenesis rates decline rapidly within the first few years of childhood. The authors were unable to detect the production of any new neurons in adults. The same patterns of neurogenesis were observed in rhesus macaques. New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus 1 , 2 , 3 , 4 , 5 . This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease 6 , 7 , 8 , 9 , 10 . In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day 11 , whereas other studies find many fewer putative new neurons 12 , 13 , 14 . Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18–77 years; n  = 17 post-mortem samples from controls; n  = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey ( Macaca mulatta ) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does