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Parenchymal border macrophages regulate CSF flow dynamics [brain]

ABSTRACT: Parenchymal border macrophages regulate CSF flow dynamics [brain]

PROVIDER: PRJNA778204 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16816734_1.fastq.gz	Fastqsanger.gz
	SRR16816734_2.fastq.gz	Fastqsanger.gz
	SRR16816735_1.fastq.gz	Fastqsanger.gz
	SRR16816735_2.fastq.gz	Fastqsanger.gz
	SRR16816736_1.fastq.gz	Fastqsanger.gz

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Parenchymal border macrophages regulate CSF flow dynamics

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Parenchymal border macrophages regulate CSF flow dynamics [leptomeningeal macs]

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Parenchymal border macrophages regulate CSF flow dynamics [brain]

Project description:Microglial cells are the resident macrophages of the brain. Perivascular macrophages (PVM) are also myeloid resident cells that are located at the interface between blood, CSF and brain in the perivascular space. Due to their strategic location and their ability to sample CSF content, we hypothesized that PVM might play a role in CSF flow. Using different fluorescent tracers injected either into the CSF (influx) or the brain parenchyma (efflux) we assessed their spatio-temporal distribution and found that ablation (using clodronate liposomes) or dysfunction (using genetic tools) of PVM alters CSF dynamics and patterns. Using single cell RNA sequencing, we found that PBMs can be divided in two sub-populations, and that one population of PBMs could interact with vascular smooth muscle cells, which allow arterial pulsations and subsequently CSF flow. Interestingly, aging results in altered PVM phenotype, and reversing this phenotype using macrophage specific grown factors reversed some of aging-associated dysfunctions of CSF flow. In summary, our results identify a new role of PVM in CSF flow and open new avenues for therapeutical applications targeting PVM in neurodegenerative diseases such as Alzheimer’s disease.

2022-08-31 | GSE188283 | GEO

Parenchymal border macrophages regulate CSF flow dynamics [5xFAD]

2022-08-31 | GSE206114 | GEO

Parenchymal border macrophages regulate CSF flow dynamics [leptomeningeal macs]

2022-08-31 | GSE188284 | GEO

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Parenchymal border macrophages regulate CSF flow dynamics

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

2022-08-31 | GSE188285 | GEO

Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration.

Project description:Parenchymal border macrophages (PBMs) reside close to the central nervous system parenchyma and regulate CSF flow dynamics. We recently demonstrated that PBMs provide a clearance pathway for amyloid-β peptide, which accumulates in the brain in Alzheimer's disease (AD). Given the emerging role for PBMs in AD, we explored how tau pathology affects the CSF flow and the PBM populations in the PS19 mouse model of tau pathology. We demonstrated a reduction of CSF flow, and an increase in an MHCII+PBM subpopulation in PS19 mice compared with WT littermates. Consequently, we asked whether PBM dysfunction could exacerbate tau pathology and tau-mediated neurodegeneration. Pharmacological depletion of PBMs in PS19 mice led to an increase in tau pathology and tau-dependent neurodegeneration, which was independent of gliosis or aquaporin-4 depolarization, essential for the CSF-ISF exchange. Together, our results identify PBMs as novel cellular regulators of tau pathology and tau-mediated neurodegeneration.

| S-EPMC10415611 | biostudies-literature

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