Dynamic Changes in the Neurogenic Potential in the Ventricular–Subventricular Zone of Common Marmoset during Postnatal Brain Development

Abstract

Even after birth, neuronal production continues in the ventricular–subventricular zone (V–SVZ) and hippocampus in many mammals. The immature new neurons (“neuroblasts”) migrate and then mature at their final destination. In humans, neuroblast production and migration toward the neocortex and the olfactory bulb (OB) occur actively only for a few months after birth and then sharply decline with age. However, the precise spatiotemporal profiles and fates of postnatally born neurons remain unclear due to methodological limitations. We previously found that common marmosets, small nonhuman primates, share many features of V–SVZ organization with humans. Here, using marmosets injected with thymidine analogue(s) during various postnatal periods, we demonstrated spatiotemporal changes in neurogenesis during development. V–SVZ progenitor proliferation and neuroblast migration toward the OB and neocortex sharply decreased by 4 months, most strikingly in a V–SVZ subregion from which neuroblasts migrated toward the neocortex. Postnatally born neurons matured within a few months in the OB and hippocampus but remained immature until 6 months in the neocortex. While neurogenic activity was sustained for a month after birth, the distribution and/or differentiation diversity was more restricted in 1-month-born cells than in the neonatal-born population. These findings shed light on distinctive features of postnatal neurogenesis in primates.

Neuroblast migration along cellular substrates in the developing porcine brain

“…In contrast to studies in ferrets, monkeys, and humans that reported a distinct decline of DCX expression, we found that the number of DCX + clusters remained constant from birth through toddlerhood in the piglet SVZ (Fig. 2) (Akter et al, 2020;Ellis et al, 2019;Paredes et al, 2016a;Sanai et al, 2011). These observations are in sharp contrast to previous findings in the piglet where DCX + cells decline with age (birth to 15 wks) and human studies were migrating immature neurons (DCX + cells) decline by 6 to 18 months of age (Morton et al, 2017;Paredes et al, 2016a;Sanai et al, 2011).…”

Positive Controls in Adults and Children Support That Very Few, If Any, New Neurons Are Born in the Adult Human Hippocampus

“…In humans, newborn neurons may take many months to mature and might maintain immature markers, such as DCX and/or PSA-NCAM, for a long time. In support of this, studies performed in sheep (Lévy et al, 2017;Piumatti et al, 2018), marmoset (Sawamoto et al, 2011;Akter et al, 2020), and macaques (Kohler et al, 2011) show that there are species differences in the maturation rate of neurons. Neurons can take up to 3 months to mature in the marmoset, compared with 3-4 weeks for mouse neurons (Petreanu and Alvarez-Buylla, 2002;Carleton et al, 2003;Zhao et al, 2006).…”

Phosphorylation of GAP-43 T172 is a molecular marker of growing axons in a wide range of mammals including primates

“…Common marmosets are currently used as a model primate in the neuroscience field [24,25]. The aforementioned results suggest that GAP-43 in primates is phosphorylated at pT181 (T181 in primates corresponds to T172 in rodents) in their developing brains.…”

“…P1 marmoset brains were fixed and immunostained as described previously [62]. We used common marmosets to which 5-ethynyl-2′-deoxyuridine (EdU) was administered for the purpose of labeling proliferating cells as previously described [24]. Marmosets were deeply anesthetized with isoflurane and transcardially perfused with PBS followed by PFA in 0.1 M PB.…”