Cholesterol biosynthesis defines oligodendrocyte precursor heterogeneity between brain and spinal cord

Khandker, Luipa; Jeffries, Marisa A.; Chang, Yun‐Juan; Mather, Marie L.; Evangelou, Angelina V.; Bourne, Jennifer N.; Tafreshi, Azadeh K.; Ornelas, Isis M.; Bozdagi-Gunal, Ozlem; Macklin, Wendy B.; Wood, Teresa L.

doi:10.1016/j.celrep.2022.110423

Cited by 27 publications

(25 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mature oligodendrocytes also are dependent on the astroglia supply of cholesterol, differently from their precursors, which show a greater autonomy as for cholesterol biosynthesis. In these cells, the biochemical processes leading to cholesterol formation are under the control of the mechanistic target of rapamycin (mTOR) pathway, as recently reported [ 29 ]. In contrast, microglia, which are the resident brain macrophages, are more deputed to store and process sphingolipids in the physiological condition, at least [ 36 ].…”

Section: Crosstalk Between Neural Cells Regulates Cholesterol Homeost...mentioning

confidence: 96%

“…Once secreted into extracellular space, cholesterol can be accepted by the surrounding cells, in particular neurons and oligodendrocytes. Both cell types, during brain development, have the ability of autonomously forming cholesterol that is lost when they reach maturity, even though this is not a valid for all neuronal types [ 29 , 30 ]. The presence of ApoE is fundamental for the neuronal uptake of cholesterol by receptor-mediated endocytosis as it behaves as a ligand of some members of the low-density lipoprotein receptor (LDLR) family (LDL receptor related protein 1 (LRP1) and LDLR) [ 31 ].…”

Section: Crosstalk Between Neural Cells Regulates Cholesterol Homeost...mentioning

confidence: 99%

See 1 more Smart Citation

Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System

Passarella

Ronci

Liberto

et al. 2022

IJMS

View full text Add to dashboard Cite

Recent studies have highlighted the mechanisms controlling the formation of cerebral cholesterol, which is synthesized in situ primarily by astrocytes, where it is loaded onto apolipoproteins and delivered to neurons and oligodendrocytes through interactions with specific lipoprotein receptors. The “cholesterol shuttle” is influenced by numerous proteins or carbohydrates, which mainly modulate the lipoprotein receptor activity, function and signaling. These molecules, provided with enzymatic/proteolytic activity leading to the formation of peptide fragments of different sizes and specific sequences, could be also responsible for machinery malfunctions, which are associated with neurological, neurodegenerative and neurodevelopmental disorders. In this context, we have pointed out that purines, ancestral molecules acting as signal molecules and neuromodulators at the central nervous system, can influence the homeostatic machinery of the cerebral cholesterol turnover and vice versa. Evidence gathered so far indicates that purine receptors, mainly the subtypes P2Y2, P2X7 and A2A, are involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s and Niemann–Pick C diseases, by controlling the brain cholesterol homeostasis; in addition, alterations in cholesterol turnover can hinder the purine receptor function. Although the precise mechanisms of these interactions are currently poorly understood, the results here collected on cholesterol–purine reciprocal control could hopefully promote further research.

show abstract

Section: Crosstalk Between Neural Cells Regulates Cholesterol Homeost...mentioning

confidence: 96%

Section: Crosstalk Between Neural Cells Regulates Cholesterol Homeost...mentioning

confidence: 99%

Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System

Passarella

Ronci

Liberto

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Here we describe analyzing isolated cells by Agilent Seahorse Cell Mito Stress Test. We have also used the cells for other downstream analyses including single-cell RNA sequencing, protein extraction and western blotting, RNA extraction and RT-PCR, and cholesterol measurement ( Khandker et al., 2022 ).…”

Section: Before You Beginmentioning

confidence: 99%

“…Isolated oligodendroglia can be used in multiple downstream analyses, and here we describe an optimized real-time metabolic assay using Agilent Seahorse Analyzer to measure mitochondrial respiration. For complete details on the use and execution of this protocol, please refer to Khandker et al. (2022) .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Live-cell metabolic analysis of oligodendroglia isolated from postnatal mouse brain and spinal cord

Khandker

Wood

2022

STAR Protocols

Self Cite

View full text Add to dashboard Cite

Endothelial Cells Mediated by STING Regulate Oligodendrogenesis and Myelination During Brain Development

Wang,

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Oligodendrocyte precursor cells (OPCs) migrate extensively using blood vessels as physical scaffolds in the developing central nervous system. Although the association of OPCs with the vasculature is critical for migration, the regulatory mechanisms important for OPCs proliferative and oligodendrocyte development are unknown. Here, a correlation is demonstrated between the developing vasculature and OPCs response during brain development. Deletion of endothelial stimulator of interferon genes (STING) disrupts angiogenesis by inhibiting farnesyl‐diphosphate farnesyltransferase 1 (FDFT1) and thereby reducing cholesterol synthesis. Furthermore, the perturbation of metabolic homeostasis in endothelial cells increases interleukin 17D production which mediates the signal transduction from endothelial cells to OPCs, which inhibits oligodendrocyte development and myelination and causes behavioral abnormalities in adult mice. Overall, these findings indicate how the endothelial STING maintains metabolic homeostasis and contributes to oligodendrocyte precursor cells response in the developing neocortex.

show abstract

Cholesterol biosynthesis defines oligodendrocyte precursor heterogeneity between brain and spinal cord

Cited by 27 publications

References 69 publications

Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System

Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System

Live-cell metabolic analysis of oligodendroglia isolated from postnatal mouse brain and spinal cord

Endothelial Cells Mediated by STING Regulate Oligodendrogenesis and Myelination During Brain Development

Contact Info

Product

Resources

About