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Microglia care for neurons through tunneling nanotubes

ABSTRACT: Microglia care for neurons through tunneling nanotubes

PROVIDER: PRJNA863248 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20693801.fastq.gz	Fastqsanger.gz
	SRR20693802.fastq.gz	Fastqsanger.gz
	SRR20693803.fastq.gz	Fastqsanger.gz
	SRR20693804.fastq.gz	Fastqsanger.gz
	SRR20693805.fastq.gz	Fastqsanger.gz

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Project description:DNA double strand breaks (DSBs) are linked to neurodegeneration and senescence. However, it is not clear how DSB-bearing neurons influence neuroinflammation associated with neurodegeneration. Here, we characterize DSB-bearing neurons from the CK-p25 mouse model of neurodegeneration using single-nucleus, bulk, and spatial transcriptomic techniques. DSB-bearing neurons enter a late-stage DNA damage response marked by NFκB-activated senescent and antiviral immune pathways. In humans, Alzheimer’s disease pathology is significantly associated with immune activation in excitatory neurons. Spatial transcriptomics reveal that regions of CK-p25 brain tissue dense with DSB-bearing neurons harbor signatures of inflammatory microglia, which is ameliorated by NFκB knock-down in neurons. Inhibition of NFκB in DSB-bearing neurons also reduces microglia activation in organotypic mouse brain slice culture. In conclusion, DSBs activate immune pathways in neurons, which in turn adopt a senescence-associated secretory phenotype to elicit microglia activation. These findings highlight a novel role for neurons in the mechanism of disease-associated neuroinflammation.

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