NG2 expressed by macrophages and oligodendrocyte precursor cells is dispensable in experimental autoimmune encephalomyelitis

Moransard, Martijn; Dann, Angela; Staszewski, Ori; Fontana, Adriano; Prinz, Marco; Suter, Tobias

doi:10.1093/brain/awr070

Cited by 40 publications

(50 citation statements)

References 50 publications

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“…The latter finding might induce a slight upregulation of [ 11 C]NE40 on the contralateral side, which might explain why no GFAP+ cells were co-labeled with CB2. The immunostaining finding that CB2-colabelled NG2+ cells were found to be round in shape suggested that they were monocytes and played a protective role [43]. In contrast, NG2+ cells without co-labeling with CB2 were thought to be oligodendrocyte precursor cells insensitive to CB2.…”

Section: Discussionmentioning

confidence: 99%

In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study

Hosoya

Fukumoto

Kakiuchi

et al. 2017

J Neuroinflammation

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BackgroundUpregulated levels of 18-kDa translocator proteins (TSPO) and type 2 endocannabinoid receptors (CB2) are considered to reflect different aspects of microglia-related neuroinflammatory responses in the brain. Relative to the increase in the TSPO expression that occurs slightly later during neuroinflammation in a proinflammatory fashion, CB2 activation is considered to relate to the neuroprotective responses that occurs predominantly at an early stage of brain disorders. These findings, however, were deduced from studies with different animal samples under different experimental settings. Here, we aimed to examined the differences in TSPO binding and CB2 availability at an early stage of stroke in the same animal using positron emission tomography (PET).MethodsWe used a total of eight Sprague-Dawley rats that underwent photothrombotic stroke surgery. The binding levels of a TSPO tracer [11C](R)PK11195 and a CB2 tracer [11C]NE40 were measured at 24 h after the surgery in the same animal using PET in combination with immunohistochemistry for CB2 and several other markers. A morphological inspection was also performed with X-ray computed tomography for small animals.ResultsThe levels of [11C]NE40 binding potential (BPND) were significantly higher in the cerebral cortical region on the lesion side than those on the non-lesion side, whereas no difference was found in the levels of [11C](R)PK11195 BPND between hemispheres. The tracer influx index (R1) data were all reduced on the lesion side irrespective of tracers. This increase in [11C]NE40 BPND was concomitant with an elevation in CB2 expression mainly within the microglia in the peri-infarct area, as shown by immunohistochemical examinations with Iba-1, CD11b/c+, and NG2+ staining.ConclusionsThe present results provide in vivo evidence of different responses of microglia occurring in the acute state of stroke. The use of the CB2 tracer [11C]NE40 allows us to evaluate the roles played by the neuroprotective aspect of microglia in acute neuroinflammatory processes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0851-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study

Hosoya

Fukumoto

Kakiuchi

et al. 2017

J Neuroinflammation

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“…This was associated with a higher expression of inducible nitric oxide synthase (iNOS), IL-1β and TNF-α, which could be reversed by treatment with NG2 siRNA. In addition, neuroinflammatory disorders, such as autoimmune encephalomyelitis, elevate the expression of NG2 in OPCs, macrophages and CNS-resident microglia, which is mediated by transforming growth factor-beta (TGF-β) [35, 36]. Inhibition of TFG-β activity by decorin [37, 38] or TGF-β1 receptor signaling by SB525334 attenuates this TGF-β-induced NG2 expression [39].…”

Section: Introductionmentioning

confidence: 99%

The regulatory mechanisms of NG2/CSPG4 expression

et al. 2017

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Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2. These regulatory factors crucially determine NG2-mediated cellular processes such as glial scar formation in the central nervous system (CNS) or tumor growth and metastasis. Therefore, they are potential targets for the establishment of novel NG2-based therapeutic strategies in the treatment of CNS injuries, cancer and other conditions of these types.

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“…These cells, also known as synantocytes or oligodendrocyte precursor cells, are the most actively cycling population of cells in the normal brain, both rodent and human [41,53], and are also the most actively cycling population after various brain lesions, including cortical stab wound injury [63,83], demyelinating lesions induced by anti-GalC antibodies [79] and in experimental autoimmune encephalitis, an animal model of multiple sclerosis [54,106]. This increase in proliferation is caused by a reduction in cell cycle length and recruitment of quiescent NG2+ cells [141].…”

Section: Fate Restricted Progenitor Cells In the Adult Brainmentioning

confidence: 99%

A review of the role of stem cells in the development and treatment of glioma

et al. 2012

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The neurosurgical management of patients with intrinsic glial cancers is one of the most rapidly evolving areas of practice. This has been fuelled by advances in surgical technique not only in cytoreduction but also in drug delivery. Further innovation will depend on a deeper understanding of the biology of the disease and an appreciation of the limitations of current knowledge. Here we review the controversial topic of cancer stem cells applied to glioma to provide neurosurgeons with a working overview. It is now recognised that the adult human brain contains regionally specified cell populations capable of self-renewal that may contribute to tumour growth and maintenance following accumulated mutational change. Tumour cells adapted to maintain growth demonstrate some stem-like characteristics and as such constitute a legitimate therapeutic target. Cellular reprogramming technologies raise the potential of developing stem cells as novel surgical tools to target disease and possibly ameliorate some of the consequences of treatment. Achieving these goals remains a significant challenge to neurosurgical oncologists, not least in challenging how we think about treating brain cancer. This review will briefly examine our understanding of adult stem cells within the brain, the evidence that they contribute to the development of brain tumours as tumour-initiating cells, and the potential implications for therapy. It will also look at the role stem cells may play in the future management of glioma.

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NG2 expressed by macrophages and oligodendrocyte precursor cells is dispensable in experimental autoimmune encephalomyelitis

Cited by 40 publications

References 50 publications

In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study

In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study

The regulatory mechanisms of NG2/CSPG4 expression

A review of the role of stem cells in the development and treatment of glioma

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