Identification of gene expression patterns critically involved in experimental autoimmune encephalomyelitis and multiple sclerosis

Herrmann, M.; Barth, Silvia; Greve, Bernhard; Schumann, Kathrin; Bartels, Andrea; Weissert, Robert

doi:10.1242/dmm.025536

Cited by 23 publications

(31 citation statements)

References 48 publications

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“…In a recent report, Herrmann et al (2016) demonstrated that CD38 was crucially involved in the pathology of EAE. CD38 expression was strongly elevated both in the encephalitogenic lymph node (LN) cells and in the CNS-infiltrating cells after induction of EAE.…”

Section: Discussionmentioning

confidence: 99%

“…In pathological conditions, CD38 has been reported to be involved in the activation of microglia and astrocytes in mouse models of glioma and traumatic brain injury, and human HIV-infected brains (Kou et al, 2009; Levy et al, 2009, 2012). However, the role of CD38 in demyelination is still unclear, although its involvement in the modulation of T-cell activation was reported in the experimental autoimmune encephalomyelitis (EAE), another widely used animal model of MS (Herrmann et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Deletion of CD38 Suppresses Glial Activation and Neuroinflammation in a Mouse Model of Demyelination

Roboon

Hattori

Ishii

et al. 2019

Front. Cell. Neurosci.

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CD38 is an enzyme that catalyzes the synthesis of cyclic adenosine diphosphate-ribose from nicotinamide adenine dinucleotide (NAD + ). We recently reported that this molecule regulates the maturation and differentiation of glial cells such as astrocytes and oligodendrocytes (OLs) in the developing brain. To analyze its role in the demyelinating situation, we employed cuprizone (CPZ)-induced demyelination model in mice, which is characterized by oligodendrocyte-specific apoptosis, followed by the strong glial activation, demyelination, and repopulation of OLs. By using this model, we found that CD38 was upregulated in both astrocytes and microglia after CPZ administration. Experiments using wild-type and CD38 knockout (KO) mice, together with those using cultured glial cells, revealed that CD38 deficiency did not affect the initial decrease of the number of OLs, while it attenuated CPZ-induced demyelination, and neurodegeneration. Importantly, the clearance of the degraded myelin and oligodendrocyte repopulation were also reduced in CD38 KO mice. Further experiments revealed that these observations were associated with reduced levels of glial activation and inflammatory responses including phagocytosis, most likely through the enhanced level of NAD + in CD38-deleted condition. Our results suggest that CD38 and NAD + in the glial cells play a critical role in the demyelination and subsequent oligodendrocyte remodeling through the modulation of glial activity and neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deletion of CD38 Suppresses Glial Activation and Neuroinflammation in a Mouse Model of Demyelination

Roboon

Hattori

Ishii

et al. 2019

Front. Cell. Neurosci.

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“…Our lab has recently characterized CD38 as a marker that is increased in inflammatory murine bone marrow-derived M(LPS + IFN-γ) macrophages and decreased in M2 macrophages compared to untreated M0 macrophages ( 47 ). CD38 upregulation is also observed in a sepsis model ( 47 ) as well as Experimental Autoimmune Encephalomyelitis (EAE), the mouse model of MS ( 48 ). Given that CD38 is a surface marker that allows live cell sorting for downstream applications, it provides an advantage over intracellular markers such as iNOS.…”

Section: Macrophage/microglia Phenotypes Function and Nomenclaturementioning

confidence: 99%

Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia

2017

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Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2 macrophages has been widely used. However, the complexity of macrophage function can only be achieved by the existence of varied, plastic and tridimensional macrophage phenotypes. Understanding how tissue macrophages integrate environmental signals via molecular programs to define pathogen/injury inflammatory responses provides an opportunity to better understand the multilayered nature of macrophages, as well as target and modulate cellular programs to control excessive inflammation. This is particularly important in MS and other neuroinflammatory diseases, where chronic inflammatory macrophage and microglial responses may contribute to pathology. Here, we perform a comprehensive review of our current understanding of how molecular pathways modulate tissue macrophage phenotype, covering both classic pathways and the emerging role of microRNAs, receptor-tyrosine kinases and metabolism in macrophage phenotype. In addition, we discuss pathway parallels in microglia, novel markers helpful in the identification of peripheral macrophages versus microglia and markers linked to their phenotype.

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“…This effect seems paradoxical since CD38 KO mice showed deficits in various learning and memory tasks such as the Morris water maze, contextual fear conditioning, and the object recognition test [65]. In the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis, CD38 deletion reduced disease severity [66]. Note that CD38 deletion was also shown to suppress glial activation and neuroinflammation in a mouse model of demyelination induced by cuprizone administration, an effect that was most likely due to enhanced level of NAD in CD38 KO mice [67].…”

Section: Cd38 Involvement In Neurodegeneration and Neuroinflammationmentioning

confidence: 99%

CD38 in Neurodegeneration and Neuroinflammation

Guerreiro¹,

Privat²,

Bressac³

et al. 2020

Cells

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Neurodegenerative diseases are characterized by neuronal degeneration as well as neuroinflammation. While CD38 is strongly expressed in brain cells including neurons, astrocytes as well as microglial cells, the role played by CD38 in neurodegeneration and neuroinflammation remains elusive. Yet, CD38 expression increases as a consequence of aging which is otherwise the primary risk associated with neurodegenerative diseases, and several experimental data demonstrated that CD38 knockout mice are protected from neurodegenerative and neuroinflammatory insults. Moreover, nicotinamide adenine dinucleotide, whose levels are tightly controlled by CD38, is a recognized and potent neuroprotective agent, and NAD supplementation was found to be beneficial against neurodegenerative diseases. The aims of this review are to summarize the physiological role played by CD38 in the brain, present the arguments indicating the involvement of CD38 in neurodegeneration and neuroinflammation, and to discuss these observations in light of CD38 complex biology.

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Identification of gene expression patterns critically involved in experimental autoimmune encephalomyelitis and multiple sclerosis

Cited by 23 publications

References 48 publications

Deletion of CD38 Suppresses Glial Activation and Neuroinflammation in a Mouse Model of Demyelination

Deletion of CD38 Suppresses Glial Activation and Neuroinflammation in a Mouse Model of Demyelination

Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia

CD38 in Neurodegeneration and Neuroinflammation

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