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Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood

Nature Neuroscience volume 9, pages 268–275 (2006)Cite this article

Abstract

Neurogenesis is known to take place in the adult brain. This work identifies T lymphocytes and microglia as being important to the maintenance of hippocampal neurogenesis and spatial learning abilities in adulthood. Hippocampal neurogenesis induced by an enriched environment was associated with the recruitment of T cells and the activation of microglia. In immune-deficient mice, hippocampal neurogenesis was markedly impaired and could not be enhanced by environmental enrichment, but was restored and boosted by T cells recognizing a specific CNS antigen. CNS-specific T cells were also found to be required for spatial learning and memory and for the expression of brain-derived neurotrophic factor in the dentate gyrus, implying that a common immune-associated mechanism underlies different aspects of hippocampal plasticity and cell renewal in the adult brain.

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Figure 1: Effects of an enriched environment on newly generated neurons and microglia in the dentate gyrus of adult rats.
Figure 2: Neurogenesis is impaired in mice with severe combined immune deficiency.
Figure 3: An enriched environment stimulates neurogenesis in Balb/c wild-type mice, but not in Balb/c SCID mice.
Figure 4: Impaired neurogenesis in T cell-deficient mice.
Figure 5: Neurogenesis is maintained by T cells specific to MBP but not by those specific to ovalbumin.
Figure 6: Spatial learning and memory are maintained by T cells specific to MBP but not by those specific to ovalbumin.
Figure 7: Expression of BDNF in the hippocampus correlates with hippocampal neurogenesis and spatial learning and memory.

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Acknowledgements

We thank S.R. Smith for editing the manuscript, A. Shapira for animal maintenance, H. Avital for graphics and O. Tchernichovsky and Y. Edelshtein for technical assistance. M.S. is the incumbent of the Maurice and Ilse Katz Professorial Chair in Neuroimmunology. This work was supported by Proneuron Biotechnologies, Weizmann Science Park, Ness-Ziona, Israel.

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Author notes

  1. Jonathan Kipnis

    Present address: Departments of Pharmacology and Ophthalmology, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska, 68198-5800, USA

  2. Yaniv Ziv and Noga Ron: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurobiology, Weizmann Institute of Science, Rehovot, 76100, Israel

    Yaniv Ziv, Noga Ron, Oleg Butovsky, Gennady Landa, Einav Sudai, Nadav Greenberg, Jonathan Kipnis & Michal Schwartz

  2. Ministry of Health, Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 84105, Israel

    Hagit Cohen

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Supplementary information

Supplementary Fig. 1

Enriched environmental housing, consisting of a specially designed cage (150 × 60 × 60 cm) containing a variety of objects, toys, a set of tunnels, and running wheels. (PDF 1956 kb)

Supplementary Fig. 2

Analyses of T-cell populations in SCID mice before and after splenocyte replenishment. (PDF 188 kb)

Supplementary Methods (PDF 77 kb)

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Ziv, Y., Ron, N., Butovsky, O. et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 9, 268–275 (2006). https://doi.org/10.1038/nn1629

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