Similar Datasets
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
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 | GSE206114 | GEO
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 | GSE188284 | GEO
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 | GSE206115 | GEO
Project description:Parenchymal border macrophages regulate CSF flow dynamics
| PRJNA778201 | ENA
Project description:Parenchymal border macrophages regulate CSF flow dynamics [5xFAD]
| PRJNA849229 | ENA
Project description:Parenchymal border macrophages regulate CSF flow dynamics [brain]
| PRJNA778204 | ENA
Project description:Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near the central nervous system (CNS) parenchyma2, and their role in CNS physiology has not been sufficiently well studied. Given their continuous interaction with the cerebrospinal fluid (CSF) and strategic positioning, we refer to these cells collectively as parenchymal border macrophages (PBMs). Here we demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation of PBMs that express high levels of CD163 and LYVE1 (scavenger receptor proteins), closely associated with the brain arterial tree, and show that LYVE1+ PBMs regulate arterial motion that drives CSF flow. Pharmacological or genetic depletion of PBMs led to accumulation of extracellular matrix proteins, obstructing CSF access to perivascular spaces and impairing CNS perfusion and clearance. Ageing-associated alterations in PBMs and impairment of CSF dynamics were restored after intracisternal injection of macrophage colony-stimulating factor. Single-nucleus RNA sequencing data obtained from patients with Alzheimer's disease (AD) and from non-AD individuals point to changes in phagocytosis, endocytosis and interferon-γ signalling on PBMs, pathways that are corroborated in a mouse model of AD. Collectively, our results identify PBMs as new cellular regulators of CSF flow dynamics, which could be targeted pharmacologically to alleviate brain clearance deficits associated with ageing and AD.
| S-EPMC9899827 | biostudies-literature
Project description:Parenchymal border macrophages regulate CSF flow dynamics [CLO depletion]
| PRJNA849230 | ENA
Project description:Parenchymal border macrophages regulate CSF flow dynamics [leptomeningeal macs]
| PRJNA778203 | ENA