Developmental profile of neurogenesis in prenatal human hippocampus: An immunohistochemical study

Abstract

Hippocampus has attracted the attention of the neuroscientists for its involvement in a wide spectrum of higher-order brain functions and pathological conditions, especially its persistent neurogenesis in subgranular zone (SGZ). The development of hippocampus was intensively investigated on animals such as rodents. However, in prenatal human hippocampus, little information on the distribution of neural stem/progenitor cells, newly generated neurons and mature neurons is available and the timetable of a series of neurogenesis event is even more obscure. So in the present study, we aim at immunohistochemically providing more information on neurogenesis in prenatal human hippocampus from 9 weeks to 32 weeks of gestation. We found that the ki67-positive cells were always detected in hippocampus from 9 weeks to 32 weeks, with a peak at 9 weeks in cornu ammonis (CA) or 14 weeks in dentate gyrus (DG). At 9 weeks the nestin-expressing cells were distributed throughout the hippocampus, with concentrated immunoreactivity in intermediate zone (IZ), marginal zone (MZ), fimbria, and relatively sparse immunoreactivity in the ventricular zone (VZ) and hippocampal plate (HP). With development, the optical density (OD) and the number of nestin-positive cells decreased gradually. At 32 weeks, there were relatively more nestin-positive cells in DG than that in CA. About DCX-positive cells, they displayed a similar distribution as nestin-positive cells (immunoreactivity concentrated in IZ, MZ, fimbria and HP) and a dramatic decrease of OD or cell number density from 9 weeks on. NeuN-positive cells, with small nuclei, were firstly found in MZ and subplate of hippocampus at 9 weeks. After 14 weeks, many NeuN-positive cells extended from subplate into HP and the density of NeuN-positive cells peaked at 22 weeks. That the immunoreactivity for NeuN was the strongest and the nuclei were the biggest at 32 weeks suggests that the neurons reach maturity gradually. Therefore this study provides an important timetable of neurogenesis in prenatal human hippocampus for the clinicians in neuroscience or pediatrics.

What Is the Relationship Between Hippocampal Neurogenesis Across Different Stages of the Lifespan?

“…In contrast, peak neurogenesis occurs prenatally in species with longer gestation periods, such as spiny mice, guinea pigs, and non-human primates, so that most DG neurons are instead generated prenatally ( Rakic and Nowakowski, 1981 ; Brunjes, 1984 ; Guidi et al, 2005 ). This shift in timing is further accentuated in humans where hippocampal neurogenesis begins in early gestation and peaks between the first and second trimester ( Yang et al, 2014 ; Cipriani et al, 2017 ; Sorrells et al, 2018 ). As a result, the protracted period of relatively low-level neurogenesis begins much earlier in the lifespan of species with longer gestation times ( Angevine, 1965 ; Schlessinger et al, 1975 ; Bayer, 1980a , b ; Rakic and Nowakowski, 1981 ; Jabès et al, 2010 ; Sorrells et al, 2018 ).…”

Nestin‐expressing cell types in the temporal lobe and hippocampus: Morphology, differentiation, and proliferative capacity

“…Nestin is a marker of progenitor cells of both neuronal and glial lineage in the developing brain and has been widely used to distinguish undifferentiated from differentiated cell types (Kawaguchi et al, 2001;von Bohlen und Halbach, 2011). Previous studies have described bipolar cells with parallel processes extending from the SVZ inward into the developing hippocampus, declining in number between 14 and 22 weeks post-conception (Yang et al, 2014). In five fetuses of up to 13 weeks gestation, we demonstrated NEC forming chains of cells and radial fibers, extending not only from the ventricular surface but also along the fimbria, the subpial surface of the hippocampus and developing hippocampal sulcus.…”

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

“…We used 59 postmortem and intraoperative samples of the human hippocampus ( Supplementary Table 1 ) to investigate the presence of progenitor cells and young neurons from fetal to adulthood stages. At 14 gestational weeks, at the peak of proliferation in the fetal dentate gyrus (DG) 15 , many dividing (Ki-67+) neural progenitors (SOX1+ (ref. 16 ) and SOX2+ (ref.…”