Department of Psychology, Vanderbilt University, Nashville, Tennessee 37240.
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
J Neurosci. 2020 Jun 10;40(24):4622-4643. doi: 10.1523/JNEUROSCI.2339-19.2020. Epub 2020 Apr 6.
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. 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.
小胶质细胞在大脑中发挥着与体积相关的重要作用,有助于神经回路的成熟和可塑性,而这些神经回路最终塑造了行为。因此,可以预期小胶质细胞在不同脑结构和不同大脑大小的物种中具有相似的细胞大小甚至分布。为了验证这一假说,我们使用免疫细胞化学方法,在从属于五个不同进化枝的雄性和雌性 33 种哺乳动物的大脑结构中,用各向同性分馏器制备的游离细胞核样本中,用 Iba1 来确定小胶质细胞的密度(细胞大小的倒数)。我们发现,小胶质细胞构成了不同脑结构以及所有被检查的哺乳动物大脑的非神经元细胞的约 7%。此外,与大脑皮质内的神经元细胞密度相比,它们在细胞密度方面变化不大,无论是在脑结构之间,还是在同一进化枝内的物种之间,或是在哺乳动物进化枝之间。因此,我们发现,一个小胶质细胞在不同脑区和物种中为少至一个和多达 100 个神经元提供服务,这取决于局部神经元密度。因此,我们得出结论,小胶质细胞添加到哺乳动物大脑中是由限制这些细胞大小的机制所控制的,并且在 2 亿多年的哺乳动物进化过程中保持保守。我们讨论了这种受限制的大小对健康和疾病中的大脑功能可能产生的后果。小胶质细胞是中枢神经系统的固有巨噬细胞,在突触再循环和维持健康和疾病中的局部环境方面具有关键功能。我们发现,不同物种的大脑和每个个体大脑的不同结构中,小胶质细胞的密度相似,这表明这些细胞在哺乳动物进化过程中保持相似的平均大小,这反过来又表明,每个小胶质细胞监测的体积在哺乳动物中保持不变。由于神经元密度在同一脑结构和物种中高度变化,我们的发现意味着,在神经元密度较高的脑结构和物种中,依赖小胶质细胞的功能恢复可能特别困难,因此每个神经元的小胶质细胞数量较少。