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Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells

Nature Neuroscience volume 13, pages 173–179 (2010)Cite this article

Abstract

Adult mammalian neurogenesis occurs in the hippocampus and the olfactory bulb, whereas neocortical adult neurogenesis remains controversial. Several occurrences of neocortical adult neurogenesis in injured neocortex were recently reported, suggesting that neural stem cells (NSCs) or neuronal progenitor cells (NPCs) that can be activated by injury are maintained in the adult brain. However, it is not clear whether or where neocortical NSCs/NPCs exist in the brain. We found NPCs in the neocortical layer 1 of adult rats and observed that their proliferation was highly activated by global forebrain ischemia. Using retrovirus-mediated labeling of layer 1 proliferating cells with membrane-targeted green fluorescent protein, we found that the newly generated neurons were GABAergic and that the neurons were functionally integrated into the neuronal circuitry. Our results suggest that layer 1 NPCs are a source of adult neurogenesis under ischemic conditions.

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Figure 1: Characterization of layer 1 proliferating cells.
Figure 2: Distribution of layer 1 proliferating cells in the control and ischemic brains.
Figure 3: Retrovirus-mediated GFP labeling of layer 1 proliferating cells.
Figure 4: Double-staining of layer 2–6 GFP-positive cells with cell markers.
Figure 5: Characterization of layer 2–6 GFP-positive cells with neurochemical markers.
Figure 6: Time course of the estimated number of layer 2–6 GFP-positive cells after ischemia.
Figure 7: Integration of new neurons into the neuronal circuitry after ischemia.

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Acknowledgements

We would like to thank T.J. Hope for a kindly gift of WPRE, and K. Takumi, M. Itoh, T. Kunieda and H. Kameda for their experimental support. This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (K.O., T.F., H.H., K.C.N., T.M., T.K. and S.N.) and the Organization for Pharmaceutical Safety and Research (S.N.), by the Cooperation Research Program of Primate Research Institute of Kyoto University (K.O.) and by the Core Research for Evolutional Science and Technology of Japan Science and Technology Agency (K.O., K.C.N., T.M., T.K. and S.N.).

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Author notes

  1. Kouichi C Nakamura

    Present address: Present address: Medical Research Council Anatomical Neuropharmacology Unit, University of Oxford, Oxford, UK, and Human Frontier Science Program, Strasbourg Cedex, France.,

Authors and Affiliations

  1. Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.,

    Koji Ohira & Tsuyoshi Miyakawa

  2. Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Koji Ohira, Takahiro Furuta, Hiroyuki Hioki, Kouichi C Nakamura, Eriko Kuramoto, Yasuyo Tanaka & Takeshi Kaneko

  3. Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan

    Koji Ohira, Nobuo Funatsu & Shun Nakamura

  4. Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Kawaguchi, Saitama, Japan.,

    Koji Ohira, Kouichi C Nakamura, Tsuyoshi Miyakawa, Takeshi Kaneko & Shun Nakamura

  5. Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan.,

    Keiko Shimizu, Takao Oishi & Motoharu Hayashi

  6. Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Myodaiji, Okazaki, Aichi, Japan.,

    Tsuyoshi Miyakawa

  7. Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo, Japan

    Shun Nakamura

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Contributions

K.O. designed and performed most of the experiments and co-wrote the paper. T.F. and H.H. made the pBS-CMV-Fyn-GFP-WPRE and pENT-Synapsin I-Fyn-GFP-WPRE plasmids. K.C.N. made guinea pig and rabbit antibodies to GFP. E.K., Y.T., N.F., K.S., T.O., M.H. and T.M. supported the experiments. T.K. and S.N. co-wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Koji Ohira or Takeshi Kaneko.

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Ohira, K., Furuta, T., Hioki, H. et al. Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells. Nat Neurosci 13, 173–179 (2010). https://doi.org/10.1038/nn.2473

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