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Gut microbiota induce neutrophil activation that aggravates stroke pathology

ABSTRACT: The study investigates the role of microbiota on neuroinflammation and stroke. RNA sequencing was performed on mouse brain samples to compare the gene expression patterns in mice who where treated with antibiotics or with sucrose control

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Smiths Lueong

PROVIDER: E-MTAB-14982 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gut microbiota induce neutrophil activation that aggravates stroke pathology

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Glial translatomes in stroke

Project description:Neuroinflammation is a hallmark of ischemic stroke, which is a leading cause of death and longterm disability. Understanding the exact cellular signaling pathways that initiate and propagate neuroinflammation after stroke will be critical for developing immunomodulatory stroke therapies. In particular, the precise mechanisms of inflammatory signaling in the clinically relevant hyperacute period, hours after stroke, have not been elucidated. We used the RiboTag technique to obtain Astrocyte IP and microglia-derived mRNA transcripts in a hyperacute (4 hours) and acute (3 days) period after stroke, as these two cell types are key modulators of acute neuroinflammation. Microglia initiated a rapid response to stroke at 4 hours by adopting an inflammatory profile associated with the recruitment of immune cells. The hyperacute Astrocyte IP profile was marked by stress response genes and transcription factors, such as Fos and Jun, involved in pro-inflammatory pathways such as TNF-α. By 3 days, microglia shift to a proliferative state and Astrocyte IPs strengthen their inflammatory response. The Astrocyte IP pro-inflammatory response at 3 days is partially driven by the upregulation of the transcription factors C/EBPβ, Spi1, and Rel, which comprise 25% of upregulated transcription factor-target interactions. Surprisingly, few sex differences across all groups were observed. Expression and log2 fold data for all sequenced genes are available on a user-friendly website for researchers to examine gene changes and generate hypotheses for stroke targets. Taken together our data comprehensively describe the Astrocyte IP and microglia-specific translatome response in the hyperacute and acute period after stroke and identify pathways critical for initiating neuroinflammation.

2023-02-14 | GSE225110 | GEO

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