TY - JOUR
T1 - Similar Microglial Cell Densities across Brain Structures and Mammalian Species
T2 - Implications for Brain Tissue Function
AU - Dos Santos, Sandra E.
AU - Medeiros, Marcelle
AU - Porfirio, Jairo
AU - Tavares, William
AU - Pessôa, Leila
AU - Grinberg, Lea
AU - Leite, Renata E.P.
AU - Ferretti-Rebustini, Renata E.L.
AU - Suemoto, Claudia K.
AU - Filho, Wilson Jacob
AU - Noctor, Stephen C.
AU - Sherwood, Chet C.
AU - Kaas, Jon H.
AU - Manger, Paul R.
AU - Herculano-Houzel, Suzana
PY - 2020/6/10
Y1 - 2020/6/10
N2 - 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.
AB - 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.
KW - cell density
KW - cell numbers
KW - comparative
KW - evolution
KW - microglia
UR - http://www.scopus.com/inward/record.url?scp=85086346785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086346785&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2339-19.2020
DO - 10.1523/JNEUROSCI.2339-19.2020
M3 - Article
C2 - 32253358
AN - SCOPUS:85086346785
VL - 40
SP - 4622
EP - 4643
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 24
ER -