Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Age-associated suppression of exploratory activity during sickness is linked to meningeal lymphatic dysfunction and microglia activation [aged]

ABSTRACT: The objective of this study is to assess the contribution of meningeal lymphatic vessels to microglia response to peripheral inflammation. Aged mice (over 2 years old) were selected as a physiologically and clinically relevant model for lymphatic dysfunction because previous reporting demonstrates meningeal lymphatic function declines with age. We sequence CD11b+ cells sorted from whole brain of aged mice two hours following 1μg IL-1β or saline vehicle intraperitoneal injection. To facilitate comparison and integration with adult mouse and experimental lymphatic ablation data, identical methods were employed.

ORGANISM(S): Mus musculus

PROVIDER: GSE168754 | GEO | 2022/06/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Age-associated suppression of exploratory activity during sickness is linked to meningeal lymphatic dysfunction and microglia activation [ablation]

Project description:The objective of this study is to assess the contribution of meningeal lymphatic vessels to microglia response to peripheral inflammation. To this end, we sequence CD11b+ cells sorted from whole brain of adult mice with intact meningeal lymphatic vessels or mice with experimental meningeal lymphatic ablation, two hours following 1μg IL-1β or saline vehicle intraperitoneal injection. The two-hour timepoint was selected for analysis because that corresponds with the peak of the behavioral response as defined by a decrease in locomotor activity and the connection between behavior and microglia activation is of particular interest in this study.

2022-06-12 | GSE168755 | GEO

Project description:The meningeal lymphatic network—housed within the dural meninges surrounding the brain— is critical for cerebrospinal fluid (CSF) drainage. Through continuous brain interstitial fluid (ISF) mixing with CSF via the glymphatic system, this lymphatic network facilitates the removal of central nervous system (CNS) waste. During aging and in Alzheimer’s disease (AD), attenuated meningeal lymphatic drainage promotes the buildup of toxic misfolded proteins—including amyloid beta—in the CNS. Alleviating this age-related meningeal lymphatic dysfunction represents a promising therapeutic strategy to alleviate AD pathology. However, the mechanisms underlying this lymphatic decline remain elusive. Here we demonstrate that age-related alterations in meningeal immunity contribute to meningeal lymphatic impairment. Single-cell RNA-sequencing of dural lymphatic endothelial cells in aged mice demonstrated a response signature to the cytokine IFNγ, which was elevated in the aged dura due to meningeal T cell accumulation. Chronic elevation of IFNγ in the meninges of young mice via AAV-mediated overexpression altered lymphatic adherans junctions and impaired CSF drainage to deep cervical lymph nodes—comparable to the deficits observed in aged mice. Direct disruption of lymphatic junctions via CSF-delivered VE-Cadherin disrupting antibodies was sufficient to phenocopy impairments in CSF drainage. Therapeutically, IFNγ neutralization in aged mice alleviated age-related impairments in meningeal lymphatic function. These data suggest manipulation of meningeal immunity as a viable therapeutic target to normalize CSF drainage in aged mice and alleviate the pathology in AD mice associated with impaired waste removal.

2023-03-10 | GSE217312 | GEO

2023-03-10 | GSE217276 | GEO

Enhanced meningeal lymphatic drainage ameliorates lipopolysaccharide-induced brain injury in aged mice

Project description:Sepsis-associated encephalopathy (SAE) is an acute cerebral dysfunction caused by sepsis. Neuroinflammation induced by sepsis is considered a potential mechanism of SAE; however, very little is known about the role of the meningeal lymphatic system in SAE. The aged mice with SAE showed a significant decrease in the drainage of OVA-647 into the dCLNs and the coverage of the Lyve-1 in the meningeal lymphatic, indicating that sepsis impaired meningeal lymphatic drainage and morphology. The meningeal lymphatic function of aged mice was more vulnerable to sepsis in comparison to young mice. Sepsis also decreased the protein levels of caspase-3 and PSD95, which was accompanied by reductions in the activity of hippocampal neurons. Microglia were significantly activated in the hippocampus of SAE mice, which was accompanied by an increase in neuroinflammation, as indicated by increases in interleukin-1 beta, interleukin-6 and Iba1 expression. Cognitive function was impaired in aged mice with SAE. However, the injection of AAV1-VEGF-C significantly increased coverage in the lymphatic system and tracer dye uptake in dCLNs, suggesting that AAV1-VEGF-C promotes meningeal lymphangiogenesis and drainage. Furthermore, AAV1-VEGF-C reduced microglial activation and neuroinflammation and improved cognitive dysfunction. Improvement of meningeal lymphatics also reduced sepsis-induced expression of disease-associated genes in aged mice. Pre-existing lymphatic dysfunction by ligating bilateral dCLNs aggravated sepsis-induced neuroinflammation and cognitive impairment.

2023-11-30 | GSE247222 | GEO

Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis

Project description:The goal of this study is to use bulk RNA-sequencing of the right brain hemisphere to observe the effects of TBI in the context of pre-existing meningeal lymphatic dysfunction in mice. We find that pre-existing meningeal lymphatic dysfunction potentiates the inflammatory response to TBI, suggesting an important role for the meningeal lymphatics in injury site drainage and proper recovery.

2020-07-25 | GSE155063 | GEO

Immunotherapy against amyloid beta is modulated by meningeal lymphatic function I

Project description:A growing body of evidence points to passive immunotherapy as a promising therapeutic strategy against AD. Herein, we show that meningeal lymphatic vasculature becomes dysfunctional in AD transgenic mice and that manipulating meningeal lymphatic drainage affects the outcome of anti-Aβ immunotherapy.

2021-03-11 | GSE141849 | GEO

Immunotherapy against amyloid beta is modulated by meningeal lymphatic function VI

2021-03-11 | GSE160220 | GEO

Immunotherapy against amyloid beta is modulated by meningeal lymphatic function V

2021-03-11 | GSE160219 | GEO

Immunotherapy against amyloid beta is modulated by meningeal lymphatic function IV

2021-03-11 | GSE160216 | GEO

Immunotherapy against amyloid beta is modulated by meningeal lymphatic function III

2021-03-11 | GSE141915 | GEO