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

Abstract

New neurons continue to be born in the subgranular zone (SGZ) in the dentate gyrus (DG) of the adult mammalian hippocampus1–5. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease6–10. In humans, some studies suggest that hundreds of new neurons are added to the adult DG every day11, while other studies find many fewer putative new neurons12–14. 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 SGZ during human fetal or postnatal development. We also find that proliferating progenitors and young neurons in the DG sharply decline in the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult normal and epileptic patients(18–77 years; n=17 postmortem; n=12 epilepsy), young neurons were not detected in the DG. In the monkey (M. mulatta) hippocampus, a proliferative SGZ was present in early postnatal life, but diminished during juvenile development as neurogenesis declined. We conclude that recruitment of young neurons to the primate hippocampus declines rapidly during the first years of life, and that DG neurogenesis does not continue, or is extremely rare, in the adult human. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved.

Human-specific features of spatial gene expression and regulation in eight brain regions

“…Both neurons and astrocytes, as well as their interactions, were implicated in learning and memory processes localized in the hippocampus (Henneberger et al 2010;Suzuki et al 2011;Ota et al 2013;Hassanpoor et al 2014;Tadi et al 2015;Gao et al 2016;Pabst et al 2016). Astrocytes were further shown to contribute to the integration of adult-born neurons in the hippocampus, although adult hippocampal neurogenesis in humans remains controversial (Krzisch et al 2015;Sultan et al 2015;Sorrells et al 2018). Moreover, the involvement of hippocampal astrocytes and astrocyte-neuron interactions in Huntington's disease, major depressive disorder, and schizophrenia have been reported (Kolomeets and Uranova 2010;Cobb et al 2016;L'Episcopo et al 2016).…”

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…Age‐related decline of cognitive function is associated with decreased numbers of neural stem cells (Fan, Wheatley, & Villeda, 2017). However, recent two researches (Boldrini et al, 2018; Sorrells et al, 2018) are contradictory to each other on whether endogenous neurogenesis exists in adult human hippocampus and new techniques need to be developed to track the newly generated neurons. Stem cell‐based therapeutics, both exogenous (transplantation) and endogenous (via factors such as growth factors that stimulate stem cells), could have important implications for both aging and AD (Limke & Rao, 2002).…”

Principles of inflammasome priming and inhibition: Implications for psychiatric disorders

“…Furthermore, by activating non-apoptotic inflammatory pathways, the NLRP3 inflammasome may support proper immune function without permanently altering neuronal structures. This feature would be evolutionary advantageous for the development of stable neural circuits in the human adult cortex and hippocampus, as their neuronal components have a limited or no potential for replacement via adult neurogenesis (Rakic, 1985; Sorrells et al, 2018). Within this context, future studies should investigate the regulatory dynamics and activity of the NLRP3 in these neurons.…”