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Journal of Neuroinflammation

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01-12-2020 | Cytokines | Research

Embryonic microglia influence developing hypothalamic glial populations

Authors: Candace M. Marsters, Dinushan Nesan, Rena Far, Natalia Klenin, Quentin J. Pittman, Deborah M. Kurrasch

Published in: Journal of Neuroinflammation | Issue 1/2020

Abstract

Background

Although historically microglia were thought to be immature in the fetal brain, evidence of purposeful interactions between these immune cells and nearby neural progenitors is becoming established. Here, we examined the influence of embryonic microglia on gliogenesis within the developing tuberal hypothalamus, a region later important for energy balance, reproduction, and thermoregulation.

Methods

We used immunohistochemistry to quantify the location and numbers of glial cells in the embryonic brain (E13.5–E17.5), as well as a pharmacological approach (i.e., PLX5622) to knock down fetal microglia. We also conducted cytokine and chemokine analyses on embryonic brains in the presence or absence of microglia, and a neurosphere assay to test the effects of the altered cytokines on hypothalamic progenitor behaviors.

Results

We identified a subpopulation of activated microglia that congregated adjacent to the third ventricle alongside embryonic Olig2+ neural progenitor cells (NPCs) that are destined to give rise to oligodendrocyte and astrocyte populations. In the absence of microglia, we observed an increase in Olig2+ glial progenitor cells that remained at the ventricle by E17.5 and a concomitant decrease of these Olig2+ cells in the mantle zone, indicative of a delay in migration of these precursor cells. A further examination of maturing oligodendrocytes in the hypothalamic grey and white matter area in the absence of microglia revealed migrating oligodendrocyte progenitor cells (OPCs) within the grey matter at E17.5, a time point when OPCs begin to slow their migration. Finally, quantification of cytokine and chemokine signaling in ex vivo E15.5 hypothalamic cultures +/− microglia revealed decreases in the protein levels of several cytokines in the absence of microglia. We assayed the influence of two downregulated cytokines (CCL2 and CXCL10) on neurosphere-forming capacity and lineage commitment of hypothalamic NPCs in culture and showed an increase in NPC proliferation as well as neuronal and oligodendrocyte differentiation.

Conclusion

These data demonstrate that microglia influence gliogenesis in the developing tuberal hypothalamus.

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Title: Embryonic microglia influence developing hypothalamic glial populations
Authors: Candace M. Marsters
Dinushan Nesan
Rena Far
Natalia Klenin
Quentin J. Pittman
Deborah M. Kurrasch
Publication date: 01-12-2020
Publisher: BioMed Central
Keyword: Cytokines
Published in: Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-020-01811-7

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Springer Medicine

Embryonic microglia influence developing hypothalamic glial populations

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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