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Unique microglia expression profile in developing white matter.

ABSTRACT: OBJECTIVE:Recently we demonstrated that amoeboid microglia in white matter regions are essential for proper oligodendrocyte homeostasis and myelinogenesis in the first postnatal week. Amoeboid microglia in the mouse corpus callosum change their activation profile within few days after postnatal day (P)7 with microglia of the cerebellum showing similar features. Here we expanded our previous transcriptional analysis and performed detailed bulk RNA sequencing of microglia from corpus callosum, cortex and cerebellum at P7, P10 and P42. The goal of this study was to identify a specific gene profile for both, white matter and grey matter microglia during development. RESULTS:Microglia in white matter regions display unique characteristics in the first postnatal week of murine life. In both the corpus callosum and cerebellum microglia show amoeboid morphology and a similar transcription profile during development including high expression of genes related to priming of microglia, phagocytosis and migration at P7; characteristics which are already lost at P10. Together these data verify our previous transcriptional data obtained by microarray analysis and enable a more complete view into white matter and grey matter microglia at different developmental stages.

SUBMITTER: Staszewski O

PROVIDER: S-EPMC6604453 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Unique microglia expression profile in developing white matter.

Staszewski Ori O Hagemeyer Nora N

BMC research notes 20190701 1

<h4>Objective</h4>Recently we demonstrated that amoeboid microglia in white matter regions are essential for proper oligodendrocyte homeostasis and myelinogenesis in the first postnatal week. Amoeboid microglia in the mouse corpus callosum change their activation profile within few days after postnatal day (P)7 with microglia of the cerebellum showing similar features. Here we expanded our previous transcriptional analysis and performed detailed bulk RNA sequencing of microglia from corpus callo ...[more]

PMID: 31262353

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Project description:Microglial activation participates in white matter injury after cerebral hypoperfusion. However, the underlying mechanism is unclear. Here, we explore whether activated microglia aggravate white matter injury via complement C3-C3aR pathway after chronic cerebral hypoperfusion. Methods: Adult male Sprague-Dawley rats (n = 80) underwent bilateral common carotid artery occlusion for 7, 14, and 28 days. Cerebral vessel density and blood flow were examined by synchrotron radiation angiography and three-dimensional arterial spin labeling. Neurobehavioral assessments, CLARITY imaging, and immunohistochemistry were performed to evaluate activation of microglia and C3-C3aR pathway. Furthermore, C3aR knockout mice were used to establish the causal relationship of C3-C3aR signaling on microglia activation and white matter injury after hypoperfusion. Results: Cerebral vessel density and blood flow were reduced after hypoperfusion (p<0.05). Spatial learning and memory deficits and white matter injury were shown (p<0.05). These impairments were correlated with aberrant microglia activation and an increase in the number of reactive microglia adhering to and phagocytosed myelin in the hypoperfusion group (p<0.05), which were accompanied by the up-regulation of complement C3 and its receptors C3aR (p<0.05). Genetic deletion of C3ar1 significantly inhibited aberrant microglial activation and reversed white matter injury after hypoperfusion (p<0.05). Furthermore, the C3aR antagonist SB290157 decreased the number of microglia adhering to myelin (p<0.05), attenuated white matter injury and cognitive deficits in chronic hypoperfusion rats (p<0.05). Conclusions: Our results demonstrated that aberrant activated microglia aggravate white matter injury via C3-C3aR pathway during chronic hypoperfusion. These findings indicate C3aR plays a critical role in mediating neuroinflammation and white matter injury through aberrant microglia activation, which provides a novel therapeutic target for the small vessel disease and vascular dementia.

Dataset Information

Unique microglia expression profile in developing white matter.

Publications

Unique microglia expression profile in developing white matter.

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