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Review
. 2012 Mar;33(2):191-206.
doi: 10.1016/j.neuro.2012.01.012. Epub 2012 Feb 2.

Microglia in the developing brain: a potential target with lifetime effects

G Jean Harry  1 , Andrew D Kraft
Affiliations
Review

Microglia in the developing brain: a potential target with lifetime effects

G Jean Harry et al. Neurotoxicology. 2012 Mar.

Abstract

Microglia are a heterogenous group of monocyte-derived cells serving multiple roles within the brain, many of which are associated with immune and macrophage like properties. These cells are known to serve a critical role during brain injury and to maintain homeostasis; yet, their defined roles during development have yet to be elucidated. Microglial actions appear to influence events associated with neuronal proliferation and differentiation during development, as well as, contribute to processes associated with the removal of dying neurons or cellular debris and management of synaptic connections. These long-lived cells display changes during injury and with aging that are critical to the maintenance of the neuronal environment over the lifespan of the organism. These processes may be altered by changes in the colonization of the brain or by inflammatory events during development. This review addresses the role of microglia during brain development, both structurally and functionally, as well as the inherent vulnerability of the developing nervous system. A framework is presented considering microglia as a critical nervous system-specific cell that can influence multiple aspects of brain development (e.g., vascularization, synaptogenesis, and myelination) and have a long term impact on the functional vulnerability of the nervous system to a subsequent insult, whether environmental, physical, age-related, or disease-related.

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Conflict of interest statement

Conflict of Interest Statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Developmental Stages Leading to Establishment of a Mature Population of Brain Microglia. Prior to late gestation (GD15-16), bone marrow derived mononuclear cells cross the blood-brain barrier (BBB) and take up residence in the brain parenchyma. These cells typically possess little cytoplasm and have small or nonexistent appendages (indicated as process-free yellow cells with blue nuclei). At early stages of colonization (GD18–19), these cells are identifiable in white matter regions (or along vascular/ ventricular margins) possessing either an amoeboid/ phagocytic morphology (orange cells) or long, highly-branched processes. During early postnatal stages (~PND5), these highly proliferative mononuclear cells are observed in both white matter and gray matter regions of the brain with either morphological phenotype. During a critical period of postnatal microglia development (PND5– PND15), the number of microglia increases dramatically. During this time, an increased ratio of ramified versus amoeboid microglia becomes apparent, with the cells having noticeably more complex process arbors and cytoplasmic material. The microglia present towards the latter part of this maturation window (~PND15) are well distributed throughout the brain, facilitating surveillance of the majority of the parenchyma; they exhibit a significantly reduced proliferative capacity; they begin to exhibit more heterogeneity (both within and across brain regions) in terms of their morphology, orientation, and process field organization; and they begin to express a somewhat modified constellation of cell surface markers. These maturation features continue such that by PND20 the adult population of microglia is fairly well established. In the absence of stimulation, these cells are highly ramified with complex process arbors encompassing the entire brain parenchyma, and they possess little to no evidence of proliferation or turnover from the systemic population. * These marker lists are not comprehensive (e.g., mature microglia express ED2− and white matter microglia are MHCII+).
Figure 2
Figure 2
Representative Iba-1+ microglia in various regions of the rat brain. (A) cerebellum (B) dentate gyrus (C) hippocampal CA1 (D) substantia nigra (E) hypothalamus (F) corpus callosum (G) parietal cortex (H) enthorinal cortex. Images from 40µm sections were scanned at 20× magnification using an Aperio Scanscope T2 Scanner (Aperio Technologies, Inc., Vista, CA) and viewed using Aperio Imagescope v. 6.25.0.1117).
Figure 3
Figure 3
Morphologies of microglia in (A) primary and slice cultures and (B) in vivo normal and (C) in vivo activated representing cells can be rated based upon the field of process arborization versus cell body to determine various stages/types of microglia.
See this image and copyright information in PMC

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