Dataset Information

Microglia: Architects of the Developing Nervous System.

ABSTRACT: Microglia are resident macrophages of the central nervous system (CNS), representing 5-10% of total CNS cells. Recent findings reveal that microglia enter the embryonic brain, take up residence before the differentiation of other CNS cell types, and become critical regulators of CNS development. Here, we discuss exciting new work implicating microglia in a range of developmental processes, including regulation of cell number and spatial patterning of CNS cells, myelination, and formation and refinement of neural circuits. Furthermore, we review studies suggesting that these cellular functions result in the modulation of behavior, which has important implications for a variety of neurological disorders.

SUBMITTER: Frost JL

PROVIDER: S-EPMC4961529 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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Microglia: Architects of the Developing Nervous System.

Frost Jeffrey L JL Schafer Dorothy P DP

Trends in cell biology 20160320 8

Microglia are resident macrophages of the central nervous system (CNS), representing 5-10% of total CNS cells. Recent findings reveal that microglia enter the embryonic brain, take up residence before the differentiation of other CNS cell types, and become critical regulators of CNS development. Here, we discuss exciting new work implicating microglia in a range of developmental processes, including regulation of cell number and spatial patterning of CNS cells, myelination, and formation and ref ...[more]

PMID: 27004698

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Project description:Prenatal Human Cytomegalovirus (HCMV) infection often causes CNS maldevelopment. In a murine model, we detect Murine Cytomegalovirus (MCMV) in brain following intra-peritoneal inoculation at birth. Infected mice show impaired cerebellar development and impaired neurologic function on a beam balance test as adults. Among developmental genes differentially regulated, hindbrain expression of the homeodomain transcription factor HOXa5 was reduced with infection, and fewer HOXa5 expressing neurons were found in vestibular nuclei. Based on the hypothesis that immune activation connects focal viral infection and global CNS maldevelopment, we defined the components of CNS immune response. Flow cytometry showed a large increase in both number and activation of CNS monocytes. Monocytes were found in close association with infected cells by immunohistochemistry (IHC). Oligonucleotide microarrays contained herein identified many differentially expressed genes related to innate immune response. Chemokines, cytokines, cell surface receptors, and proteases are some of the many immunological genes shown to be differentially regulated by MCMV infection. These results together show that MCMV infection induces a complex immune response associated with changes in developmental gene expression and lasting neurologic defecit. Keywords: disease state comparison (virus infection) and competetive hybridization for expression analysis Previous work empirically determined the kinetics of viral spread to and replication in the Balb-C murine CNS. Balb-C mice were inoculated intra-peritoneally at birth, and harvested at 5, 8, 12, and 21 days post inoculation for cerebellar experiments. Controls were mock infected with vehicle (DMEM cell growth media) and harvested at the same timepoints. Each microarray was a two channel MEEBO array, upon which labeled and reverse transcribed cDNA from 3 pooled infected cerebella and three pooled uninfected cerebella competetively hybridized. Three unique biological replicates were performed with day 5 cDNA, 5 unique biological replicates at day 8, 5 unique biological replicates at day 12, and 4 unique biological replicates at day 21. For the analysis, colors channels were seperated and treated as independent hybridizations. However, since the experiments were dual channel, the primary data may be employed to generate ratio based measurements, and each sample is provided a corresponding number that can be used to pair the processed data and derive ratios (mock 3, infected 3). Mice were similarly inoculated and harvested at 5, 15, and 21 days post natal for liver tissue analysis. Inoculation was performed by injection with a microsyringe of 50ul titered virus delivering 500-1000 PFU per animal.

Dataset Information

Microglia: Architects of the Developing Nervous System.

Publications

Microglia: Architects of the Developing Nervous System.

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