Reciprocal Interactions between Oligodendrocyte Precursor Cells and the Neurovascular Unit in Health and Disease

Pfeiffer, Friederike

doi:10.3390/cells11121954

Cited by 7 publications

(4 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To do this, we generated NG2DsRed × CX 3 CR1 +/GFP mice to enable robust visualization of microglia (CX 3 CR1 +/GFP ) and pericytes (NG2DsRed) in fixed brain tissue (Figure 1a,b ). We note that the NG2DsRed line has previously been used to visualize oligodendrocyte progenitor cells (OPCs (Hartmann et al, 2015 ; Nemes‐Baran et al, 2020 ), Supplementary Figure 2 ), and that some OPCs have been found to reside on the vasculature (Pfeiffer, 2022 ; Pfeiffer et al, 2021 ). It is therefore possible OPCs could be mistaken for pericytes when using this genetic line.…”

Section: Resultsmentioning

confidence: 93%

“…Data were processed in Microsoft Excel and all statistical analysis was performed using GraphPad Prism 9.3.1 (GraphPad, USA). Prior to statistical analysis, data underwent outlier testing using a ROUT test Figure 2), and that some OPCs have been found to reside on the vasculature (Pfeiffer, 2022;Pfeiffer et al, 2021). It is therefore possible…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Microglia directly associate with pericytes in the central nervous system

Morris

Foster

Courtney

et al. 2023

Glia

View full text Add to dashboard Cite

Cerebral blood flow (CBF) is important for the maintenance of brain function and its dysregulation has been implicated in Alzheimer's disease (AD). Microglia associations with capillaries suggest they may play a role in the regulation of CBF or the bloodbrain-barrier (BBB). We explored the relationship between microglia and pericytes, a vessel-resident cell type that has a major role in the control of CBF and maintenance of the BBB, discovering a spatially distinct subset of microglia that closely associate with pericytes. We termed these pericyte-associated microglia (PEM). PEM are present throughout the brain and spinal cord in NG2DsRed Â CX 3 CR1 +/GFP mice, and in the human frontal cortex. Using in vivo two-photon microscopy, we found microglia residing adjacent to pericytes at all levels of the capillary tree and found they can maintain their position for at least 28 days. PEM can associate with pericytes lacking astroglial endfeet coverage and capillary vessel width is increased beneath pericytes with or without an associated PEM, but capillary width decreases if a pericyte loses a PEM. Deletion of the microglia fractalkine receptor (CX 3 CR1) did not disrupt the association between pericytes and PEM. Finally, we found the proportion of microglia that are PEM declines in the superior frontal gyrus in AD. In summary, we identify microglia that specifically associate with pericytes and find these are reduced in number in AD, which may be a novel mechanism contributing to vascular dysfunction in neurodegenerative diseases.

show abstract

Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Microglia directly associate with pericytes in the central nervous system

Morris

Foster

Courtney

et al. 2023

Glia

View full text Add to dashboard Cite

show abstract

“…We also note recent reports by Yang et al 58 on AD-relevant activity of CR1 within perivascular macrophages (PVM). Given complex reciprocal interactions between oligodendrocytes and the neurovascular unit 59,60 , simultaneous evaluation of CR1 and AD GWAS loci in PVM and oligodendrocytes may illuminate a shared mechanism that could explain the observed CNS as well as hematological effects in a parsimonious manner. Further investigation of whether rs679515 is associated with alterations of peripheral CR1 may also represent a fruitful path for future study.…”

Section: Discussionmentioning

confidence: 99%

A public resource of single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease

Wang,

Antone,

Alsop

et al. 2023

Preprint

View full text Add to dashboard Cite

The emergence of technologies that can support high-throughput profiling of single cell transcriptomes offers to revolutionize the study of brain tissue from persons with and without Alzheimer's disease (AD). Integration of these data with additional complementary multiomics data such as genetics, proteomics and clinical data provides powerful opportunities to link observed cell subpopulations and molecular network features within a broader disease-relevant context. We report here single nucleus RNA sequencing (snRNA-seq) profiles generated from superior frontal gyrus cortical tissue samples from 101 exceptionally well characterized, aged subjects from the Banner Brain and Body Donation Program in combination with whole genome sequences. We report findings that link common AD risk variants with CR1 expression in oligodendrocytes as well as alterations in peripheral hematological lab parameters, with these observations replicated in an independent, prospective cohort study of ageing and dementia. We also observed an AD-associated CD83(+) microglial subtype with unique molecular networks that encompass many known regulators of AD-relevant microglial biology, and which are associated with immunoglobulin IgG4 production in the transverse colon. These findings illustrate the power of multi-tissue molecular profiling to contextualize snRNA-seq brain transcriptomics and reveal novel disease biology. The transcriptomic, genetic, phenotypic, and network data resources described within this study are available for access and utilization by the scientific community.

show abstract

“…Oligodendrocyte precursor cells (OPCs) have crucial functions in BBB maintenance and vessel formation throughout life. In return, they receive trophic support [ 52 ]. By producing and maintaining the myelin sheath as an insulator around axons, they contribute to the critical transmission of nerve impulses.…”

Section: The Neurovascular Unit In Healthmentioning

confidence: 99%

Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models

Brandl,

Reindl

2023

IJMS

View full text Add to dashboard Cite

The blood–brain barrier, which is formed by tightly interconnected microvascular endothelial cells, separates the brain from the peripheral circulation. Together with other central nervous system-resident cell types, including pericytes and astrocytes, the blood–brain barrier forms the neurovascular unit. Upon neuroinflammation, this barrier becomes leaky, allowing molecules and cells to enter the brain and to potentially harm the tissue of the central nervous system. Despite the significance of animal models in research, they may not always adequately reflect human pathophysiology. Therefore, human models are needed. This review will provide an overview of the blood–brain barrier in terms of both health and disease. It will describe all key elements of the in vitro models and will explore how different compositions can be utilized to effectively model a variety of neuroinflammatory conditions. Furthermore, it will explore the existing types of models that are used in basic research to study the respective pathologies thus far.

show abstract

Reciprocal Interactions between Oligodendrocyte Precursor Cells and the Neurovascular Unit in Health and Disease

Cited by 7 publications

References 125 publications

Microglia directly associate with pericytes in the central nervous system

Microglia directly associate with pericytes in the central nervous system

A public resource of single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease

Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models

Contact Info

Product

Resources

About