Elsevier

Neuroscience Research

Volume 167, June 2021, Pages 64-69
Neuroscience Research

Review article
Neurogenesis and neuronal migration in the postnatal ventricular-subventricular zone: Similarities and dissimilarities between rodents and primates

https://doi.org/10.1016/j.neures.2020.06.001Get rights and content

Highlights

  • Postnatal neurogenesis is more limited in primates than in rodents.

  • Migrating immature neurons follow different paths by different mechanisms.

  • Brain repair by manipulating neurogenesis is harder in primates than in rodents.

Abstract

The ventricular-subventricular zone (V-SVZ) is located in the walls of the lateral ventricles and produces new neurons in the postnatal brain of mammals, including humans. Immature new neurons called “neuroblasts” generated by neural stem cells in the V-SVZ migrate toward their final destinations and contribute to brain development and plasticity. In this review, we describe recent progress in understanding the similarities and dissimilarities in postnatal neurogenesis and neuronal migration between rodents and primates. In rodents, most new V-SVZ-derived neurons migrate along the rostral migratory stream towards the olfactory bulb, where they differentiate into interneurons. In contrast, in humans, the extensive migration of new neurons towards the neocortex continues for several months after birth and might be involved in the development of the expanded neocortex. The mode of migration and the fate of neuroblasts seem to change depending on their environment, destination, and roles in the brain. A better understanding of these similarities and differences between rodents and primates will help translate important findings from animal models and may contribute to the development of clinical strategies for brain repair.

Introduction

In the 1960s, Altman and colleagues suggested that new neurons can be born in the adult mammalian brain (Altman, 2011). Following these pioneering studies, the mechanisms of adult neurogenesis have been extensively studied over the decades. It is now well-accepted that new neurons are produced after birth in two brain regions: the ventricular-subventricular zone (V-SVZ), located in the walls of the lateral ventricles, and the subgranular zone (SGZ) in the dentate gyrus of the hippocampus, with other regions of the central nervous system losing their neurogenic capacity after birth. In these two neurogenic niches, new neurons are produced from progenitors, or neural stem cells (NSCs). Although the basis of adult neurogenesis is similar among different mammalian species, the extent of neurogenesis and directions of neuroblast migration vary from rodents to primates as the brain becomes relatively larger and more complex (Akter et al., 2020; Dennis et al., 2016; Doetsch et al., 1997; Gil-Perotin et al., 2009; Kornack and Rakic, 2001; Lois et al., 1996; Lois and Alvarez-Buylla, 1994; Paredes et al., 2016a; Pencea et al., 2001; Sanai et al., 2011; Sawamoto et al., 2011; Wang et al., 2011).

Most of our knowledge regarding adult neurogenesis comes from studies using rodents owing to the expanded possibilities of their experimental use. Our understanding of adult neurogenesis in humans and non-human primates is gradually increasing. Consequently, we now know that some of the features of adult neurogenesis are not shared among rodents, humans, and non-human primates. In rodents and non-human primates, SGZ NSCs in the postnatal dentate gyrus continuously produce new neurons; however, the extent of postnatal neurogenesis in the human hippocampal dentate gyrus is under debate (Spalding et al., 2013; Sorrells et al., 2018; Boldrini et al., 2018). To solve the unanswered questions regarding adult neurogenesis in humans, new methodologies to study the generation of new neurons in adult human are needed as discussed in recent reviews (Kempermann et al., 2018; Snyder, 2018).

In contrast to the new neurons that are locally generated and differentiated within the hippocampus, those generated in the V-SVZ have greater potential to migrate long distances to other brain regions. Recent studies suggest mechanisms for neurogenesis and neuronal migration are also different among rodents, humans, and non-human primates. Therefore, in this review, we focus on the similarities and differences of postnatal V-SVZ neurogenesis between rodents and primates and its involvement in the endogenous repair processes.

Section snippets

V-SVZ organization

The V-SVZ is composed of ependymal cells, neuroblasts, astrocytes, and transit-amplifying cells in both rodents and primates (Doetsch et al., 1997; Gil- Perotin et al., 2009; Sawamoto et al., 2011). Ependymal cells form an epithelial layer that lines the ventricles. The V-SVZ astrocytes have been identified as the primary neural progenitors, i.e., NSCs in the adult brain (Doetsch et al., 1999). NSCs proliferate slowly and give rise to rapidly-dividing intermediate progenitors, which produce

Spatiotemporal patterns of V-SVZ neurogenesis

V-SVZ neuroblasts differentiate into interneurons in distinct layers of the OB. The majority of these interneurons are granule cells (GCs) in the granular cell layer, while the rest are periglomerular cells (PGCs) in the glomerular layer. GCs can be subdivided into three subtypes based on the location of their cell bodies: intermediate, deep, and superficial GCs (Price and Powell, 1970). PGCs can also be subdivided into three subtypes based on the expression of calretinin (CR), calbindin (CB),

Migration of V-SVZ-derived neuroblasts in the postnatal brain

In rodents, a large number of migrating neuroblasts are produced from NSCs and migrate through the rostral migratory stream (RMS) as an elongated, chain-like aggregate to reach their final destination, the olfactory bulb (OB), where they differentiate into interneurons (Doetsch et al., 1997,1999; Lois et al., 1996; Lois and Alvarez-Buylla, 1994). Conversely, there are very few migrating neuroblasts in the human RMS, which appear as singlets or in pairs, but do not form a chain, after 2 years of

Limits and challenges for endogenous repair in the primate brain

Neurogenesis in the adult V-SVZ is a potential target for regenerative therapies of the injured brain. After brain injury to areas such as the striatum and cortex, various chemokines and growth factors are upregulated, which stimulate the proliferation of NSCs and transit-amplifying cells in the V-SVZ and migration of neuroblasts (Fujioka et al., 2019; Sawada and Sawamoto, 2013). A successful approach for regenerating neuronal circuits for functional recovery after an injury has been reported

Conclusion

Neuroscientists show deep interest in how the human brain works and how it differs from those of other species. However, there are various technical limitations in studying the development of the human brain. Non-human primates can, therefore, be useful as model animals because they are more similar to humans than rodents. Considering the recent technical advances in generating transgenic primates (Sasaki et al., 2009; Park and Silva, 2019), modern genetic techniques, currently only applicable

Acknowledgments

We apologize to all whose work we could not cite because of space limitations. We are grateful to Jose Manuel Garcia-Verdugo, Chikako Nakajima, Mercedes Paredes, Masato Sawada, and Vicente Herranz Perez for their valuable comments, and Trent Rogers (Edanz Group) for editing drafts of this manuscript. This study was supported by research grants from the Japan Society for the Promotion of Science KAKENHI (17H01392, 17H05750, 19H04757, 19H04785, 18KK0213 [to K.S.], 17K07114[to N.K.]), the

References (59)

  • M. Akter et al.

    Dynamic changes in the neurogenic potential in the ventricular-subventricular zone of common marmoset during postnatal brain development

    Cereb. Cortex

    (2020)
  • J. Altman

    The Discovery of adult mammalian neurogenesis

  • K. Azim et al.

    Early decline in progenitor diversity in the marmoset lateral ventricle

    Cereb. Cortex

    (2013)
  • R. Batista-Brito et al.

    The distinct temporal origins of olfactory bulb interneuron subtypes

    J. Neurosci.

    (2008)
  • M. Boldrini et al.

    Human hippocampal neurogenesis persists throughout aging

    Cell Stem Cell

    (2018)
  • L. Bonfanti et al.

    Adult neurogenesis in mammals – a theme with many variations

    Eur. J. Neurosci.

    (2011)
  • S. Bragado Alonso et al.

    An increase in neural stem cells and olfactory bulb adult neurogenesis improves discrimination of highly similar odorants

    EMBO J.

    (2019)
  • M.S. Brill et al.

    A dlx2- and pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb

    J. Neurosci.

    (2008)
  • M.S. Brill et al.

    Adult generation of glutamatergic olfactory bulb interneurons

    Nat. Neurosci.

    (2009)
  • E.C. Bunk et al.

    Cellular organization of adult neurogenesis in the Common Marmoset

    Aging Cell

    (2011)
  • S. De Marchis et al.

    Generation of distinct types of periglomerular olfactory bulb interneurons during development and in adult mice: implication for intrinsic properties of the subventricular zone progenitor population

    J. Neurosci.

    (2007)
  • C.V. Dennis et al.

    Human adult neurogenesis across the ages: an immunohistochemical study

    Neuropathol. Appl. Neurobiol.

    (2016)
  • F. Doetsch et al.

    Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain

    J. Neurosci.

    (1997)
  • R. Fiorelli et al.

    Adding a spatial dimension to postnatal ventricular-subventricular zone neurogenesis

    Development

    (2015)
  • S. Gil-Perotin et al.

    Ultrastructure of the subventricular zone in Macaca fascicularis and evidence of a mouse-like migratory stream

    J. Comp. Neurol.

    (2009)
  • M.A. Hack et al.

    Neuronal fate determinants of adult olfactory bulb neurogenesis

    Nat. Neurosci.

    (2005)
  • N. Horie et al.

    Transplanted stem cell-secreted vascular endothelial growth factor effects poststroke recovery, inflammation, and vascular repair

    Stem Cells

    (2011)
  • D. Inta et al.

    Neurogenesis and widespread forebrain migration of distinct GABAergic neurons from the postnatal subventricular zone

    Proc. Natl. Acad. Sci. U. S. A.

    (2008)
  • K. Jin et al.

    Evidence for stroke-induced neurogenesis in the human brain

    Proc. Natl. Acad. Sci. U. S. A.

    (2006)
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