Adult Neurogenesis in Humans- Common and Unique Traits in Mammals

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Abstract

New neurons generated in the adult brain have been shown in rodents to mediate specific functions, including neural plasticity. This Essay discusses recent work on human adult neurogenesis, examining how it compares to that in other mammals.

Abstract

New neurons are continuously generated in specific regions in the adult brain. Studies in rodents have demonstrated that adult-born neurons have specific functional features and mediate neural plasticity. Data on the extent and dynamics of adult neurogenesis in adult humans are starting to emerge, and there are clear similarities and differences compared to other mammals. Why do these differences arise? And what do they mean?

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Neuronal replacement from endogenous precursors in the adult brain after stroke.

Andreas Arvidsson, Tove Collin, Deniz Kirik … (2002)

In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans.

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Corridors of Migrating Neurons in Human Brain and Their Decline during Infancy

Nader Sanai, Thuhien Nguyen, Rebecca A. Ihrie … (2011)

The subventricular zone (SVZ) of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb (OB) 1–6 . Along the walls of the lateral ventricles, immature neuronal progeny migrate in tangentially-oriented chains that coalesce into a rostral migratory stream (RMS) connecting the SVZ to the OB. The adult human SVZ, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes 7 . Some of these SVZ astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report finds few SVZ proliferating cells and rare migrating immature neurons in the RMS of adult humans 7 . In contrast, a subsequent study indicates robust proliferation and migration in the human SVZ and RMS 8,9 . Here, we find that the infant human SVZ and RMS contain an extensive corridor of migrating immature neurons before 18 months of age, but, contrary to previous reports 8 , this germinal activity subsides in older children and is nearly extinct by adulthood. Surprisingly, during this limited window of neurogenesis, not all new neurons in the human SVZ are destined for the OB – we describe a major migratory pathway that targets the prefrontal cortex in humans. Together, these findings reveal robust streams of tangentially migrating immature neurons in human early postnatal SVZ and cortex. These pathways represent potential targets of neurological injuries affecting neonates.

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A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain.

Shaoyu Ge, Chih-Hao Yang, Kuei-Sen Hsu … (2007)

Active adult neurogenesis occurs in discrete brain regions of all mammals and is widely regarded as a neuronal replacement mechanism. Whether adult-born neurons make unique contributions to brain functions is largely unknown. Here we systematically characterized synaptic plasticity of retrovirally labeled adult-born dentate granule cells at different stages during their neuronal maturation. We identified a critical period between 1 and 1.5 months of the cell age when adult-born neurons exhibit enhanced long-term potentiation with increased potentiation amplitude and decreased induction threshold. Furthermore, such enhanced plasticity in adult-born neurons depends on developmentally regulated synaptic expression of NR2B-containing NMDA receptors. Our study demonstrates that adult-born neurons exhibit the same classic critical period plasticity as neurons in the developing nervous system. The transient nature of such enhanced plasticity may provide a fundamental mechanism allowing adult-born neurons within the critical period to serve as major mediators of experience-induced plasticity while maintaining stability of the mature circuitry.

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Author and article information

Journal

Journal ID (nlm-ta): PLoS Biol

Journal ID (iso-abbrev): PLoS Biol

Journal ID (publisher-id): plos

Journal ID (pmc): plosbiol

Title: PLoS Biology

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Print): 1544-9173

ISSN (Electronic): 1545-7885

Publication date Collection: January 2015

Publication date (Electronic): 26 January 2015

Volume: 13

Issue: 1

Electronic Location Identifier: e1002045

Affiliations

[1 ]Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden

[2 ]Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Author notes

The authors have declared that no competing interests exist.

* E-mail: jonas.frisen@ 123456ki.se

Article

Publisher ID: PBIOLOGY-D-14-02564

DOI: 10.1371/journal.pbio.1002045

PMC ID: 4306487

PubMed ID: 25621867

SO-VID: 4e39333e-2d5f-4cdb-b95f-114cdc3b1aaf

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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Figures: 4, Tables: 0, Pages: 12

Funding

Work in the authors’ laboratory was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Karolinska Institute, Tobias Stiftelsen, AFA Försäkringar, the Swedish Foundation for Strategic Research, the Strategic Research Programme in Stem Cells and Regenerative Medicine at Karolinska Institutet (StratRegen), the ERC, Torsten Söderbergs Stiftelse and Knut och Alice Wallenbergs Stiftelse. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Adult Neurogenesis in Humans- Common and Unique Traits in Mammals

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Most cited references 45

Neuronal replacement from endogenous precursors in the adult brain after stroke.

Corridors of Migrating Neurons in Human Brain and Their Decline during Infancy

A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain.

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