Immune cell regulation of glia during CNS injury and disease

Greenhalgh, Andrew D.; David, Sam; Bennett, F. Chris

doi:10.1038/s41583-020-0263-9

Cited by 286 publications

(227 citation statements)

References 235 publications

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“…One interesting finding is "Selenoamino acid metabolism". Since selenium-dependent enzymes prevent and reverse oxidative damage in brain, our findings support that selenium-dependent enzymes could mediate the relation between antioxidants and SCZ/ASD [34,35]. The REACTOME pathways that are over-represented by the 65 genes with microglia-specific-DE p-values smaller than 0.05 in both CMC-SCZ and UCLA-ASD studies.…”

Section: Concordant Microglia-specific De Genes Between Scz and Asdsupporting

confidence: 66%

Cell type-aware analysis of RNA-seq data

Jin

Chen

Lin

et al. 2020

Preprint

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Differential expression using RNA sequencing data of bulk tissue samples (bulk RNA-seq) is a very popular and effective approach to study many biomedical problems. However, most tissue samples are composed of different cell types. Differential expression analysis without accounting for cell type composition cannot separate the changes due to cell type composition or cell type-specific expression. In addition, cell type-specific signals may be masked or even misrepresented, especially for relatively rare cell types. We propose a new framework to address these limitations: Cell Type Aware analysis of RNA-seq (CARseq). After evaluating its performance in simulations, we apply CARseq to compare gene expression of schizophrenia/autism subjects versus controls. Our results show that these two neurodevelopmental disorders differ from each other in terms of cell type composition changes and genes related with different types of neurotransmitter receptors were differentially expressed in neuron cells. We also discover some overlapping signals of differential expression in microglia, supporting the two diseases' similarity through immune regulation.

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Section: Concordant Microglia-specific De Genes Between Scz and Asdsupporting

confidence: 66%

Cell type-aware analysis of RNA-seq data

Jin

Chen

Lin

et al. 2020

Preprint

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“…In the adult brain, microglia are essential surveyors and phagocytes, maintaining homeostasis in the brain [ 53 , 54 , 55 , 56 , 57 ]. Only a limited number of genes and proteins are found in human and rodent glia, and therefore the direct translation of results from animal to human studies is restricted [ 58 , 59 ].…”

Section: Neurons and Glial Cells In The Brainmentioning

confidence: 99%

“…Microglia are extremely dynamic and evidence for this behavior was first recorded in real-time using confocal microscopy [ 66 ]. The mobility and chemical mediators they produce allow for an intense cross-talk between astrocytes and other glial cells and neurons [ 31 , 48 , 56 , 67 , 68 ]. Dendrimers with intrinsic anti-inflammatory activity, or those with incorporated anti-inflammatory drugs, are useful nanotechnological tools to modulate neural cell cross-talks [ 31 ].…”

Section: Neurons and Glial Cells In The Brainmentioning

confidence: 99%

Dendrimers as Modulators of Brain Cells

2020

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Nanostructured hyperbranched macromolecules have been extensively studied at the chemical, physical and morphological levels. The cellular structural and functional complexity of neural cells and their cross-talk have made it rather difficult to evaluate dendrimer effects in a mixed population of glial cells and neurons. Thus, we are at a relatively early stage of bench-to-bedside translation, and this is due mainly to the lack of data valuable for clinical investigations. It is only recently that techniques have become available that allow for analyses of biological processes inside the living cells, at the nanoscale, in real time. This review summarizes the essential properties of neural cells and dendrimers, and provides a cross-section of biological, pre-clinical and early clinical studies, where dendrimers were used as nanocarriers. It also highlights some examples of biological studies employing dendritic polyglycerol sulfates and their effects on glia and neurons. It is the aim of this review to encourage young scientists to advance mechanistic and technological approaches in dendrimer research so that these extremely versatile and attractive nanostructures gain even greater recognition in translational medicine.

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“…Pro-inflammation microglia synthesis and release pro-inflammatory molecules such as iNOS, CD32, IL-1β; The anti-inflammation microglia synthesis and release anti-inflammatory molecules such as YM-1, CD206 and IL10. Pro-inflammation is detrimental and does further damage to the ischemia tissue, while the anti-inflammation is neuroprotective and promotes functional recovery [7][8][9]. Thus, attenuating pro-inflammation and enhancing anti-inflammation in microglia would avoid severe inflammatory response and thereby protect against neuronal death after cerebral ischemia-reperfusion (I/R) injury.…”

Section: Introductionmentioning

confidence: 99%

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury

et al. 2020

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Neuroinflammation is a secondary response following ischemia stroke. Arginine is a non-essential amino acid that has been shown to inhibit acute inflammatory reaction. In this study we show that arginine treatment decreases neuronal death after rat cerebral ischemia/reperfusion (I/R) injury and improves functional recovery of stroke animals. We also show that arginine suppresses inflammatory response in the ischemic brain tissue and in the cultured microglia after OGD insult. We further provide evidence that the levels of HIF-1α and LDHA are increased after rat I/R injury and that arginine treatment prevents the elevation of HIF-1α and LDHA after I/R injury. Arginine inhibits inflammatory response through suppression of HIF-1α and LDHA in the rat ischemic brain tissue and in the cultured microglia following OGD insult, and protects against ischemic neuron death after rat I/R injury by attenuating HIF-1α/LDHA-mediated inflammatory response. Together, these results indicate a possibility that arginine-induced neuroprotective effect may be through the suppression of HIF-1α/LDHA-mediated inflammatory response in microglia after cerebral ischemia injury.

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Immune cell regulation of glia during CNS injury and disease

Cited by 286 publications

References 235 publications

Cell type-aware analysis of RNA-seq data

Cell type-aware analysis of RNA-seq data

Dendrimers as Modulators of Brain Cells

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury

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