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Similar Microglial Cell Densities across Brain Structures and Mammalian Species: Implications for Brain Tissue Function.

  • Dos Santos, Sandra E1
  • Medeiros, Marcelle2
  • Porfirio, Jairo2
  • Tavares, William3
  • Pessôa, Leila3
  • Grinberg, Lea4, 5
  • Leite, Renata E P5
  • Ferretti-Rebustini, Renata E L5, 6
  • Suemoto, Claudia K5
  • Filho, Wilson Jacob5
  • Noctor, Stephen C7
  • Sherwood, Chet C8, 9
  • Kaas, Jon H1
  • Manger, Paul R10
  • Herculano-Houzel, Suzana11, 12, 13
  • 1 Department of Psychology, Vanderbilt University, Nashville, Tennessee 37240.
  • 2 Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil. , (Brazil)
  • 3 Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil. , (Brazil)
  • 4 Memory and Aging Center, University of California San Francisco, San Francisco, California 94158.
  • 5 Biobank for Aging Studies, Universidade de São Paulo, São Paulo, SP 01246-903, Brazil. , (Brazil)
  • 6 Escola de Enfermagem da Universidade de São Paulo, São Paulo, SP 01246-903, Brazil. , (Brazil)
  • 7 School of Medicine, University of California at Davis, Davis, California 95817.
  • 8 Department of Anthropology, George Washington University, Washington, DC 20052.
  • 9 Center for the Advanced Study of Human Paleobiology, George Washington University, Washington, DC 20052.
  • 10 School of Anatomical Sciences, University of the Witwatersrand, Braamfontein, 2000, South Africa, Johannesburg. , (South Africa)
  • 11 Department of Psychology, Vanderbilt University, Nashville, Tennessee 37240 [email protected]
  • 12 Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37212.
  • 13 Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee 37232.
Published Article
Journal of Neuroscience
Society for Neuroscience
Publication Date
Jun 10, 2020
DOI: 10.1523/JNEUROSCI.2339-19.2020
PMID: 32253358


Microglial cells play essential volume-related actions in the brain that contribute to the maturation and plasticity of neural circuits that ultimately shape behavior. Microglia can thus be expected to have similar cell sizes and even distribution both across brain structures and across species with different brain sizes. To test this hypothesis, we determined microglial cell densities (the inverse of cell size) using immunocytochemistry to Iba1 in samples of free cell nuclei prepared with the isotropic fractionator from brain structures of 33 mammalian species belonging to males and females of five different clades. We found that microglial cells constitute ∼7% of non-neuronal cells in different brain structures as well as in the whole brain of all mammalian species examined. Further, they vary little in cell density compared with neuronal cell densities within the cerebral cortex, across brain structures, across species within the same clade, and across mammalian clades. As a consequence, we find that one microglial cell services as few as one and as many as 100 neurons in different brain regions and species, depending on the local neuronal density. We thus conclude that the addition of microglial cells to mammalian brains is governed by mechanisms that constrain the size of these cells and have remained conserved over 200 million years of mammalian evolution. We discuss the probable consequences of such constrained size for brain function in health and disease.SIGNIFICANCE STATEMENT Microglial cells are resident macrophages of the CNS, with key functions in recycling synapses and maintaining the local environment in health and disease. We find that microglial cells occur in similar densities in the brains of different species and in the different structures of each individual brain, which indicates that these cells maintain a similar average size in mammalian evolution, suggesting in turn that the volume monitored by each microglial cell remains constant across mammals. Because the density of neurons is highly variable across the same brain structures and species, our finding implies that microglia-dependent functional recovery may be particularly difficult in those brain structures and species with high neuronal densities and therefore fewer microglial cells per neuron. Copyright © 2020 the authors.

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