Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inflammatory subtypes of T cells, particularly Th17 cells, are deleterious in diseases such as multiple sclerosis.
“inflammatory subtypes of T cells, particularly Th17 cells, are clearly deleterious in diseases such as multiple sclerosis (9–11, 24)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [24]
Immune deficiency in mice causes cognitive impairments that are reversed by replenishment of CD4+ T cells.
“immune deficiency in mice causes cognitive impairments that are reversed by replenishment of CD4+ T cells (23–27)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [24]
CD4+ T cells are necessary for hippocampal neurogenesis in adult rodents.
“CD4+ T cells are necessary for hippocampal neurogenesis in adult rodents”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [24]
Th17 cells are deleterious to the CNS.
“Th17 cells are deleterious to the CNS”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [24]
Immune-deficient mice have impaired adult neurogenesis even when housed in environmentally enriched conditions, suggesting that immune molecules, potentially originating from microglia, are necessary for adult neurogenesis.
“Immune-deficient mice have impaired adult neurogenesis, even when housed in environmentally enriched conditions which typically increase stem cell proliferation, suggesting that immune molecules, potentially originating from microglia, are necessary for adult neurogenesis (Ziv et al., 2006).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Ziv et al., 2006
Cites
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827 · see citing works
More hippocampal neurons in adult mice living in an enriched environment
Kempermann, G., Kuhn, H. G., & Gage, F. H. (1997) · Nature · doi:10.1038/386493a0 · Cited by 3,513 · see citing works
Running enhances neurogenesis, learning, and long-term potentiation in mice
van Praag, H., Christie, B. R., Sejnowski, T. J., & Gage, F. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.23.13427 · Cited by 2,904 · see citing works
Synaptic Plasticity and Memory: An Evaluation of the Hypothesis
Martin, S. J., Grimwood, P. D., & Morris, R. G. M. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.649 · Cited by 2,794 · see citing works
Inflammatory Blockade Restores Adult Hippocampal Neurogenesis
Monje, M. L., Toda, H., & Palmer, T. D. (2003) · Science · doi:10.1126/science.1088417 · Cited by 2,426 · see citing works
Learning enhances adult neurogenesis in the hippocampal formation
Gould, E., Beylin, A., Tanapat, P., Reeves, A., & Shors, T. J. (1999) · Nature Neuroscience · doi:10.1038/6365 · Cited by 2,157 · see citing works
Neurogenesis in the adult is involved in the formation of trace memories
Shors, T. J., Miesegaes, G. R., Beylin, A. V., Zhao, M., Rydel, T. A., & Gould, E. (2001) · Nature · doi:10.1038/35066584 · Cited by 2,014 · see citing works
Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus
Cameron, H. A., & Mckay, R. D. G. (2001) · Journal of Comparative Neurology · doi:10.1002/cne.1040 · Cited by 1,585 · see citing works
Inflammation is detrimental for neurogenesis in adult brain
Ekdahl, C. T., Claasen, J.-H., Bonde, S., Kokaia, Z., & Lindvall, O. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2234031100 · Cited by 1,559 · see citing works
Álvarez-Buylla, A., & Lim, D. A. (2004) · Neuron · doi:10.1016/s0896-6273(04)00111-4 · Cited by 1,320 · see citing works
Age-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,180 · see citing works
T‐lymphocyte entry into the central nervous system
Hickey, W. F., Hsu, B. L., & Kimura, H. (1991) · Journal of Neuroscience Research · doi:10.1002/jnr.490280213 · Cited by 1,176 · see citing works
Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis
Pluchino, S., Quattrini, A., Brambilla, E., Gritti, A., Salani, G., Dina, G., Galli, R., Carro, U. D., Amadio, S., Bergami, A., et al. (2003) · Nature · doi:10.1038/nature01552 · Cited by 1,071 · see citing works
Kerschensteiner, M., Gallmeier, E., Behrens, L., Vargas-Leal, V., Misgeld, T., Klinkert, W. E. F., Kolbeck, R., Hoppe, E., Oropeza-Wekerle, R. L., Bartke, I., et al. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.5.865 · Cited by 1,019 · see citing works
Trejo, J. L., Carro, E., & Torres-Alemán, I. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01628.2001 · Cited by 1,017 · see citing works
Butovsky, O., Ziv, Y., Schwartz, A., Landa, G., Talpalar, A. E., Pluchino, S., Martino, G., & Schwartz, M. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.10.006 · Cited by 923 · see citing works
Self-citationAutoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy
Moalem‐Taylor, G., Leibowitz‐Amit, R., Yoles, E., Mor, F., Cohen, I. R., & Schwartz, M. (1999) · Nature Medicine · doi:10.1038/4734 · Cited by 882 · see citing works
Self-citationBlunt, T., Finnie, N., Taccioli, G. E., Smith, G. C. M., Demengeot, J., Gottlieb, T. M., Mizuta, R., Varghese, A. J., Alt, F. W., Jeggo, P. A., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90360-7 · Cited by 865 · see citing works
A role for adult neurogenesis in spatial long-term memory
Snyder, J. S., Hong, N. S., McDonald, R. J., & Wojtowicz, J. M. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.10.009 · Cited by 854 · see citing works
Neurogenesis may relate to some but not all types of hippocampal‐dependent learning
Shors, T. J., Townsend, D. A., Zhao, M., Kozorovitskiy, Y., & Gould, E. (2002) · Hippocampus · doi:10.1002/hipo.10103 · Cited by 853 · see citing works
Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis
Brown, J., Cooper‐Kuhn, C. M., Kempermann, G., Van Praag, H., Winkler, J., Gage, F. H., & Kuhn, H. G. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02647.x · Cited by 809 · see citing works
Scharfman, H., Goodman, J., Macleod, A., Phani, S., Antonelli, C., & Croll, S. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2004.11.016 · Cited by 719 · see citing works
The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms
Engelhardt, B., & Ransohoff, R. M. (2005) · Trends in Immunology · doi:10.1016/j.it.2005.07.004 · Cited by 676 · see citing works
Early life experience alters response of adult neurogenesis to stress
Mirescu, C., Peters, J. D., & Gould, E. (2004) · Nature Neuroscience · doi:10.1038/nn1290 · Cited by 625 · see citing works
Pull, S. L., Doherty, J. M., Mills, J. C., Gordon, J. I., & Stappenbeck, T. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405979102 · Cited by 605 · see citing works
Carro, E., Trejo, J. L., Busiguina, S., & Torres-Aleman, I. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-15-05678.2001 · Cited by 601 · see citing works
Mizuno, M., Yamada, K., Olariu, A., Nawa, H., & NABESHIMA, T. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-18-07116.2000 · Cited by 549 · see citing works
Kipnis, J., Cohen, H., Cardon, M., Ziv, Y., & Schwartz, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402268101 · Cited by 510 · see citing works
Self-citationMigration and differentiation of neural precursor cells can be directed by microglia
Aarum, J., Sandberg, K., Haeberlein, S. L. B., & Persson, M. A. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2237050100 · Cited by 450 · see citing works
Adult neurogenesis and repair of the adult CNS with neural progenitors, precursors, and stem cells
Emsley, J. G., Mitchell, B. D., Kempermann, G., & Macklis, J. D. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.04.002 · Cited by 398 · see citing works
Butovsky, O., Talpalar, A. E., Ben‐Yaakov, K., & Schwartz, M. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.03.005 · Cited by 368 · see citing works
Self-citationProtective Autoimmunity Is a Physiological Response to CNS Trauma
Yoles, E., Hauben, E., Palgi, O., Agranov, E., Gothilf, A., Cohen, A., Kuchroo, V. K., Cohen, I. R., Weiner, H. L., & Schwartz, M. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-11-03740.2001 · Cited by 344 · see citing works
Self-citationProduction of Neurotrophins by Activated T Cells: Implications for Neuroprotective Autoimmunity
Moalem‐Taylor, G., Gdalyahu, A., Shani, Y., Otten, U., Lazarovici, P., Cohen, I. R., & Schwartz, M. (2000) · Journal of Autoimmunity · doi:10.1006/jaut.2000.0441 · Cited by 337 · see citing works
Self-citationImmune signalling in neural development, synaptic plasticity and disease
Boulanger, L. M., & Shatz, C. J. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1428 · Cited by 334 · see citing works
Ehninger, D. (2003) · Cerebral Cortex · doi:10.1093/cercor/13.8.845 · Cited by 314 · see citing works
Olivares–Villagómez, D., Wang, Y., & Lafaille, J. J. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.10.1883 · Cited by 294 · see citing works
Chun, J. J. M., Schatz, D. G., Oettinger, M. A., Jaenisch, R., & Baltimore, D. (1991) · Cell · doi:10.1016/0092-8674(91)90220-s · Cited by 285 · see citing works
Kipnis, J., Mizrahi, T., Hauben, E., Shaked, I., Shevach, E. M., & Schwartz, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.232565399 · Cited by 265 · see citing works
Self-citationShaked, I., Tchoresh, D., Gersner, R., Meiri, G., Mordechai, S., Xiao, X., Hart, R. P., & Schwartz, M. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02954.x · Cited by 210 · see citing works
Self-citationHauben, E., Agranov, E., Gothilf, A., Nevo, U., Cohen, A., Smirnov, I., Steinman, L., & Schwartz, M. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12837 · Cited by 208 · see citing works
Self-citationCohen, H., Ziv, Y., Cardon, M., Kaplan, Z., Matar, M. A., Gidron, Y., Schwartz, M., & Kipnis, J. (2006) · Journal of Neurobiology · doi:10.1002/neu.20249 · Cited by 173 · see citing works
Self-citationSchwartz, M., & Kipnis, J. (2001) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(01)01993-1 · Cited by 167 · see citing works
Self-citationButovsky, O., Hauben, E., & Schwartz, M. (2001) · The FASEB Journal · doi:10.1096/fj.00-0550fje · Cited by 110 · see citing works
Self-citationSchwartz, M., & Kipnis, J. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02322-0 · Cited by 98 · see citing works
Self-citationMuhallab, S., Lundberg, C., Gielen, A. W., Lidman, O., Svenningsson, A., Piehl, F., & Olsson, T. P. (2002) · Scandinavian Journal of Immunology · doi:10.1046/j.0300-9475.2002.01038.x · Cited by 62 · see citing works
HIV-1-associated dementia: a basic science and clinical perspective.
Diesing, T. S., Swindells, S., Gelbard, H. A., & Gendelman, H. E. (2002) · PubMed · Cited by 54 · see citing works
Planting and pruning in the brain: MHC antigens involved in synaptic plasticity?
Wekerle, H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408495101 · Cited by 29 · see citing works
Gaillard, R.-C., Daneva, T., Hadid, R., et al. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09586.x · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493 · see citing works
Self-citationMicroglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110 · see citing works
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676 · see citing works
Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions
Ming, G.-L., & Song, H. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.001 · Cited by 2,651 · see citing works
Enriched environments, experience-dependent plasticity and disorders of the nervous system
Nithianantharajah, J., & Hannan, A. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1970 · Cited by 1,771 · see citing works
Microglia Shape Adult Hippocampal Neurogenesis through Apoptosis-Coupled Phagocytosis
Sierra, A., Encinas, J. M., Deudero, J. J. P., Chancey, J. H., Enikolopov, G., Overstreet-Wadiche, L. S., Tsirka, S. E., & Maletic-Savatic, M. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.014 · Cited by 1,622 · see citing works
Neuroinflammation: The Devil Is in the Details
DiSabato, D. J., Quan, N., & Godbout, J. P. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13607 · Cited by 1,640 · see citing works
Immune modulation of learning, memory, neural plasticity and neurogenesis
Yirmiya, R., & Goshen, I. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.10.015 · Cited by 1,483 · see citing works
Microglia development follows a stepwise program to regulate brain homeostasis
Matcovitch-Natan, O., Winter, D. R., Giladi, A., Vargas Aguilar, S., Spinrad, A., Sarrazin, S., Ben-Yehuda, H., David, E., Zelada González, F., Perrin, P., et al. (2016) · Science · doi:10.1126/science.aad8670 · Cited by 1,180 · see citing works
Self-citationMicroglial signatures and their role in health and disease
Butovsky, O., & Weiner, H. L. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0057-5 · Cited by 1,046 · see citing works
Self-citationMicroglia: new roles for the synaptic stripper
Kettenmann, H., Kirchhoff, F., & Verkhratsky, A. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.023 · Cited by 1,173 · see citing works
Bridging animal and human models of exercise-induced brain plasticity
Voss, M. W., Vivar, C., Kramer, A. F., & van Praag, H. (2013) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.08.001 · Cited by 1,030 · see citing works
Microglia Regulate the Number of Neural Precursor Cells in the Developing Cerebral Cortex
Cunningham, C. L., Martínez-Cerdeño, V., & Noctor, S. C. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3441-12.2013 · Cited by 976 · see citing works
Haroon, E., Raison, C. L., & Miller, A. H. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.205 · Cited by 1,000 · see citing works
Depression as a Microglial Disease
Yirmiya, R., Rimmerman, N., & Reshef, R. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.001 · Cited by 944 · see citing works
Regulation of learning and memory by meningeal immunity: a key role for IL-4
Derecki, N. C., Cardani, A. N., Yang, C. H., Quinnies, K. M., Crihfield, A., Lynch, K. R., & Kipnis, J. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091419 · Cited by 800 · see citing works
Self-citationBrain inflammation and adult neurogenesis: The dual role of microglia
Ekdahl, C. T., Kokaia, Z., & Lindvall, O. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2008.06.052 · Cited by 801 · see citing works
Kreisel, T., Frank, M. G., Licht, T., Reshef, R., Ben-Menachem-Zidon, O., Baratta, M. V., Maier, S. F., & Yirmiya, R. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.155 · Cited by 663 · see citing works
The role of immune dysfunction in the pathophysiology of autism
Onore, C., Careaga, M., & Ashwood, P. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.08.007 · Cited by 635 · see citing works
Aging-induced type I interferon response at the choroid plexus negatively affects brain function
Baruch, K., Deczkowska, A., David, E., Castellano, J. M., Miller, O., Kertser, A., Berkutzki, T., Barnett-Itzhaki, Z., Bezalel, D., Wyss-Coray, T., et al. (2014) · Science · doi:10.1126/science.1252945 · Cited by 615 · see citing works
Self-citationDhabhar, F. S., Malarkey, W. B., Neri, E., & McEwen, B. S. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.05.008 · Cited by 589 · see citing works
“We suggest that the brain, which is also a site for immune cell traffic (Gottfried-Blackmore et al., 2009; Miller, 2010; Silver et al., 1996; Ziv et al., 2006), and where immune cells are now thought to play a role in facilitating homeostasis, neurogenesis, and function (Ziv et al., 2006), may also…”
BackgroundInfluentialIL-4 in the brain: a cytokine to remember
Gadani, S. P., Cronk, J. C., Norris, G. T., & Kipnis, J. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1202246 · Cited by 549 · see citing works
Self-citationMöhle, L., Mattei, D., Heimesaat, M. M., Bereswill, S., Fischer, A., Alutis, M., French, T., Hambardzumyan, D., Matzinger, P., Dunay, I. R., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.074 · Cited by 470 · see citing works
Microglia: actively surveying and shaping neuronal circuit structure and function
Wake, H., Moorhouse, A. J., Miyamoto, A., & Nabekura, J. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2012.11.007 · Cited by 448 · see citing works
Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma?
Danese, A., & J Lewis, S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.198 · Cited by 393 · see citing works
Cardiovascular fitness is associated with cognition in young adulthood
Åberg, M. A. I., Pedersen, N. L., Torén, K., Svartengren, M., Bäckstrand, B., Johnsson, T., Cooper-Kuhn, C. M., Åberg, N. D., Nilsson, M., & Kuhn, H. G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905307106 · Cited by 382 · see citing works
Thored, P., Heldmann, U., Gomes‐Leal, W., Gisler, R., Darsalia, V., Taneera, J., Nygren, J. M., Jacobsen, S. W., Ekdahl, C. T., Kokaia, Z., et al. (2009) · Glia · doi:10.1002/glia.20810 · Cited by 378 · see citing works
Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition
Pasciuto, E., Burton, O. T., Roca, C. P., Lagou, V., Rajan, W. D., Theys, T., Mancuso, R., Tito, R. Y., Kouser, L., Callaerts-Vegh, Z., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.026 · Cited by 368 · see citing works
González, H., Elgueta, D., Montoya, A., & Pacheco, R. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.07.012 · Cited by 352 · see citing works
Schwartz, M., & Baruch, K. (2014) · The EMBO Journal · doi:10.1002/embj.201386609 · Cited by 349 · see citing works
Self-citationAlves de Lima, K., Rustenhoven, J., & Kipnis, J. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-102319-103410 · Cited by 348 · see citing works
Self-citationWolf, S. A., Steiner, B., Akpinarli, A., Kammertoens, T., Nassenstein, C., Braun, A., Blankenstein, T., & Kempermann, G. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0801218 · Cited by 329 · see citing works
Neuroplastic changes in depression: A role for the immune system
Eyre, H., & Baune, B. T. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.03.019 · Cited by 319 · see citing works
Hidden wounds? inflammatory links between childhood trauma and psychopathology
Danese, A., & Baldwin, J. R. (2017) · Annual Review of Psychology · doi:10.1146/annurev-psych-010416-044208 · Cited by 286 · see citing works
Altered T cell responses in children with autism
Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Pessah, I. N., & Van de Water, J. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.09.002 · Cited by 281 · see citing works
Arcuri, C., Mecca, C., Bianchi, R., Giambanco, I., & Donato, R. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00191 · Cited by 279 · see citing works
Butovsky, O. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26836 · Cited by 261 · see citing works
Self-citationInflammatory T helper 17 cells promote depression-like behavior in mice
Beurel, E., Harrington, L. E., & Jope, R. S. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.09.021 · Cited by 254 · see citing works
Hertz‐Picciotto, I., Park, H., Dostal, M., Kocan, A., Trnovec, T., & Sram, R. (2008) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2007.00190.x · Cited by 253 · see citing works
Pro-cognitive properties of T cells
Kipnis, J., Gadani, S., & Derecki, N. C. (2012) · Nature Reviews Immunology · doi:10.1038/nri3280 · Cited by 246 · see citing works
Self-citationAging and Rejuvenation of Neural Stem Cells and Their Niches
Navarro Negredo, P., Yeo, R. W., & Brunet, A. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.07.002 · Cited by 246 · see citing works
Systemic inflammatory cells fight off neurodegenerative disease
Schwartz, M., & Shechter, R. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.71 · Cited by 240 · see citing works
Self-citationMicroglia Modulate Hippocampal Neural Precursor Activity in Response to Exercise and Aging
Vukovic, J., Colditz, M. J., Blackmore, D. G., Ruitenberg, M. J., & Bartlett, P. F. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5925-11.2012 · Cited by 241 · see citing works
Adult neurogenesis, glia, and the extracellular matrix
Cope, E. C., & Gould, E. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.03.023 · Cited by 236 · see citing works
Peripheral immune system in aging and Alzheimer’s disease
Cao, W., & Zheng, H. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0284-2 · Cited by 214 · see citing works
Sexually divergent induction of microglial-associated neuroinflammation with hippocampal aging
Mangold, C. A., Wronowski, B., Du, M., Masser, D. R., Hadad, N., Bixler, G. V., Brucklacher, R. M., Ford, M. M., Sonntag, W. E., & Freeman, W. M. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0920-8 · Cited by 203 · see citing works
Adaptive immunity affects learning behavior in mice
Brynskikh, A., Warren, T., Zhu, J., & Kipnis, J. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.12.008 · Cited by 221 · see citing works
Self-citationTranscriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease
Chapuis, J., Hot, D., Hansmannel, F., Kerdraon, O., Ferreira, S., Hubans, C., Maurage, C. A., Huot, L., Bensemain, F., Laumet, G., et al. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.10 · Cited by 201 · see citing works
Fenn, A. M., Henry, C. J., Huang, Y., Dugan, A., & Godbout, J. P. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.10.003 · Cited by 198 · see citing works
Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms
Heuer, L., Ashwood, P., Schauer, J., Goines, P., Krakowiak, P., Hertz‐Picciotto, I., Hansen, R., Croen, L. A., Pessah, I. N., & Van de Water, J. (2008) · Autism Research · doi:10.1002/aur.42 · Cited by 190 · see citing works
Effects of Microglia on Neurogenesis
Sato, K. (2015) · Glia · doi:10.1002/glia.22858 · Cited by 187 · see citing works
Jin, W.-N., Shi, K., He, W., Sun, J.-H., Van Kaer, L., Shi, F.-D., & Liu, Q. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00745-w · Cited by 179 · see citing works
The benefits of neuroinflammation for the repair of the injured central nervous system
Yong, H. Y. F., Rawji, K. S., Ghorbani, S., Xue, M., & Yong, V. W. (2019) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0223-3 · Cited by 190 · see citing works
Speisman, R. B., Kumar, A., Rani, A., Foster, T. C., & Ormerod, B. K. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.09.013 · Cited by 187 · see citing works
Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10
Xie, L., Choudhury, G. R., Winters, A., Yang, S., & Jin, K. (2015) · European Journal of Immunology · doi:10.1002/eji.201444823 · Cited by 185 · see citing works
Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment
Singhal, G., Jaehne, E. J., Corrigan, F., & Baune, B. T. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00097 · Cited by 186 · see citing works
Kohman, R. A., DeYoung, E. K., Bhattacharya, T. K., Peterson, L. N., & Rhodes, J. S. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.10.006 · Cited by 176 · see citing works
Haslund‐Vinding, J., McBean, G., Jaquet, V, & Vilhardt, F. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13425 · Cited by 169 · see citing works
The Choroid Plexus in Healthy and Diseased Brain
Kaur, C., Rathnasamy, G., & Ling, E.-A. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlv030 · Cited by 176 · see citing works
Zeng, J., Bao, T., Yang, K., Zhu, X., Wang, S., Xiang, W., Ge, A., Zeng, L., & Ge, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1047550 · Cited by 175 · see citing works
Graphene quantum dots conjugated neuroprotective peptide improve learning and memory capability
Xiao, S., Zhou, D., Luan, P., Gu, B., Feng, L., Fan, S., Liao, W., Fang, W., Yang, L., Tao, E., et al. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.08.021 · Cited by 169 · see citing works
Learning and memory … and the immune system
Marin, I., & Kipnis, J. (2013) · Learning & Memory · doi:10.1101/lm.028357.112 · Cited by 166 · see citing works
Self-citationMyocardial aging as a T-cell–mediated phenomenon
Ramos, G. C., van den Berg, A., Nunes-Silva, V., Weirather, J., Peters, L., Burkard, M., Friedrich, M., Pinnecker, J., Abeßer, M., Heinze, K. G., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621047114 · Cited by 168 · see citing works
Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?
Mayne, K., White, J. A., McMurran, C. E., Rivera, F. J., & de la Fuente, A. G. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.572090 · Cited by 167 · see citing works
Functions of microglia in the central nervous system—beyond the immune response
Wake, H., Moorhouse, A. J., & Nabekura, J. (2011) · Neuron Glia Biology · doi:10.1017/s1740925x12000063 · Cited by 167 · see citing works
Biscaro, B., Lindvall, O., Tesco, G., Ekdahl, C. T., & Nitsch, R. M. (2012) · Neurodegenerative Diseases · doi:10.1159/000330363 · Cited by 164 · see citing works
Understanding the Role of T Cells in CNS Homeostasis
Ellwardt, E., Walsh, J. T., Kipnis, J., & Zipp, F. (2016) · Trends in Immunology · doi:10.1016/j.it.2015.12.008 · Cited by 156 · see citing works
Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation
Miller, A. H., Haroon, E., & Felger, J. C. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.167 · Cited by 152 · see citing works
Maggi, L. (2011) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2011.00022 · Cited by 149 · see citing works
Expression of Toll-Like Receptors in the Developing Brain
Kaul, D., Habbel, P., Derkow, K., Krüger, C., Franzoni, E., Wulczyn, F. G., Bereswill, S., Nitsch, R., Schott, E., Veh, R., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037767 · Cited by 141 · see citing works
Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice
Brachman, R. A., Lehmann, M. L., Maric, D., & Herkenham, M. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2278-14.2015 · Cited by 130 · see citing works
Immune-Based Therapy for Spinal Cord Repair: Autologous Macrophages and Beyond
Schwartz, M., & Yoles, E. (2006) · Journal of Neurotrauma · doi:10.1089/neu.2006.23.360 · Cited by 131 · see citing works
Self-citationInteraction Between Sleep and the Immune Response in Drosophila: A Role for the NFκB Relish
Williams, J. A., Sathyanarayanan, S., Hendricks, J. C., & Sehgal, A. (2007) · Sleep · doi:10.1093/sleep/30.4.389 · Cited by 126 · see citing works
Béland, L.-C., Markovinovic, A., Jakovac, H., De Marchi, F., Bilic, E., Mazzini, L., Kriz, J., & Munitic, I. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa124 · Cited by 125 · see citing works
Reducing post-traumatic anxiety by immunization
Lewitus, G. M., Cohen, H., & Schwartz, M. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.05.002 · Cited by 123 · see citing works
Self-citationXu, H., Gelyana, E., Rajsombath, M., Yang, T., Li, S., & Selkoe, D. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1023-16.2016 · Cited by 109 · see citing works
Vaccination as a Novel Approach for Treating Depressive Behavior
Lewitus, G. M., Wilf-Yarkoni, A., Ziv, Y., Shabat-Simon, M., Gersner, R., Zangen, A., & Schwartz, M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.07.014 · Cited by 109 · see citing works
Self-citationMicroglia regulate hippocampal neurogenesis during chronic neurodegeneration
De Lucia, C., Rinchon, A., Olmos-Alonso, A., Riecken, K., Fehse, B., Boche, D., Perry, V. H., & Gomez-Nicola, D. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.11.001 · Cited by 110 · see citing works
The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?
Doty, K. R., Guillot-Sestier, M.-V., & Town, T. (2015) · Brain Research · doi:10.1016/j.brainres.2014.09.008 · Cited by 104 · see citing works
Gebara, E., Sultan, S., Kocher-Braissant, J., & Toni, N. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00145 · Cited by 102 · see citing works
Glial cell activation in response to electroconvulsive seizures
Jansson, L., Wennström, M., Johanson, A., & Tingström, A. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.06.007 · Cited by 99 · see citing works
Immunity and cognition: what do age-related dementia, HIV-dementia and ‘chemo-brain’ have in common?
Kipnis, J., Derecki, N. C., Yang, C., & Scrable, H. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.07.007 · Cited by 90 · see citing works
Self-citationRegulation of the neurodegenerative process associated to Parkinson's disease by CD4+ T-cells
González, H., Contreras, F., & Pacheco, R. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9618-9 · Cited by 70 · see citing works
Social Defeat Modulates T Helper Cell Percentages in Stress Susceptible and Resilient Mice
Ambrée, O., Ruland, C., Zwanzger, P., Klotz, L., Baune, B. T., Arolt, V., Scheu, S., & Alferink, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143512 · Cited by 54 · see citing works
Detection of IL-17 and IL-23 in Plasma Samples of Children with Autism
Enstrom, A., Onore, C., Hertz-Picc, I., Hansen, R., Croen, L., Water, J. V. D., & Ashwood, P. (2008) · American Journal of Biochemistry and Biotechnology · doi:10.3844/ajbbsp.2008.114.120 · Cited by 51 · see citing works
Nelson, P. A., Sage, J. R., Wood, S. C., Davenport, C. M., Anagnostaras, S. G., & Boulanger, L. M. (2013) · Learning & Memory · doi:10.1101/lm.031351.113 · Cited by 49 · see citing works
Learning from the nexus of autoimmunity and cancer
Mangani, D., Yang, D., & Anderson, A. C. (2023) · Immunity · doi:10.1016/j.immuni.2023.01.022 · Cited by 33 · see citing works
Microglia express functional 11β‐hydroxysteroid dehydrogenase type 1
Gottfried‐Blackmore, A., Sierra, A., Mcewen, B. S., Ge, R., & Bulloch, K. (2010) · Glia · doi:10.1002/glia.21007 · Cited by 27 · see citing works
Muth, C., Schröck, K., Madore, C., Hartmann, K., Fanek, Z., Butovsky, O., Glatzel, M., & Krasemann, S. (2017) · Brain Pathology · doi:10.1111/bpa.12441 · Cited by 23 · see citing works
Self-citationPathogenesis, Animal Models, and Drug Discovery of Alzheimer’s Disease
Xia, Z.-D., Ma, R.-X., Wen, J.-F., Zhai, Y.-F., Wang, Y.-Q., Wang, F.-Y., Liu, D., Zhao, X.-L., Sun, B., Jia, P., et al. (2023) · Journal of Alzheimer's Disease · doi:10.3233/jad-230326 · Cited by 19 · see citing works
Leardini-Tristao, M., Charles, A.-L., Lejay, A., Pizzimenti, M., Meyer, A., Estato, V., Tibiriçá, E., Andres, E., & Geny, B. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8050653 · Cited by 17 · see citing works
“after 6 weeks of environmental enrichment [87].”
Xin, J., Mesnard, N. A., Beahrs, T., Wainwright, D. A., Serpe, C. J., Alexander, T. D., Sanders, V. M., & Jones, K. J. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.02.011 · Cited by 17 · see citing works
Neurotherapeutic Implications of Brain-Immune Interactions
Felger, J. C., & Miller, A. H. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.213 · Cited by 11 · see citing works
TREM2-dependent senescent microglia conserved in aging and Alzheimer’s disease
Rachmian, N., Medina, S., Cherqui, U., Akiva, H., Deitch, D., Edilbi, D., Croese, T., Salame, T., Peralta Ramos, J., Cahalon, L., et al. (2023) · doi:10.1101/2023.03.20.533401 · Cited by 6 · see citing works
Self-citation
- Authors
- Ziv, Y., Ron, N., Butovsky, O., Landa, G., Sudai, E., Greenberg, N., Cohen, H., Kipnis, J., & Schwartz, M.
- Affiliations
- Weizmann Institute of Science (IL)
- Ben-Gurion University of the Negev (IL)
- Corresponding author
- Kipnis, Jonathan
- Schwartz, Michal
- Venue
- Nature Neuroscience
- Published
- 2006-01-15
- Volume
- 9
- Issue
- 2
- Pages
- 268-275
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2108398194
- Cited by
- 1,209
- References
- 48
- Citations by year
- 2026: 22 · 2025: 46 · 2024: 44 · 2023: 40 · 2022: 62 · 2021: 70 · 2020: 55 · 2019: 63 · 2018: 50 · 2017: 59 · 2016: 83 · 2015: 57 · 2014: 71 · 2013: 63 · 2012: 73
- FWCI
- 21.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- adult neurogenesis, hippocampus, T cells, microglia, spatial learning, memory, environmental enrichment, immunodeficient mice, brain-derived neurotrophic factor, dentate gyrus, hippocampal plasticity
- MeSH terms
- Animals, Cell Division, Hippocampus, Immunohistochemistry, Male, Memory, Neuronal Plasticity, Spatial Behavior, Stem Cells, T-Lymphocytes, Rats, Sprague-Dawley, Microglia, Maze Learning, Brain-Derived Neurotrophic Factor, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
