Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology

Ponath, Gerald; Ramanan, Sriram; Mubarak, Mayyan; Housley, William; Lee, Seung‐Hoon; Sahinkaya, F. Rezan; Vortmeyer, Alexander O.; Raine, Cedric S.; Pitt, David

doi:10.1093/brain/aww298

Cited by 172 publications

(181 citation statements)

References 38 publications

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“…The destructive nature of the white matter lesion was also evident from the widespread phagocytosis by gitter cells (activated microglia and blood‐derived monocytes) of abundant MBP from myelin sheath breakdown. A subset of astrocytes also showed MBP engulfment, and myelin uptake has recently been suggested to be an early response of astrocytes in diseases with myelin injury, which may also exacerbate the myelin loss …”

Section: Discussionmentioning

confidence: 97%

Large felid leucoencephalomyelopathy in a Sumatran tiger (Panthera tigris sumatrae) from an Australian zoo

Hanshaw¹,

McLelland

Manavis

et al. 2019

Aust Veterinary J

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Case report The clinicopathological features of a case consistent with large felid leucoencephalomyelopathy are described in a 19‐year‐old, zoo‐based Sumatran tiger in which degenerative vertebral disease, renal insufficiency, diaphragmatic hernia and cataracts were comorbid. The principal presenting sign was ataxia, with concurrent deterioration of vertebral stiffness and vision loss. Histological features included marked destruction of the white matter, the formation of large, bizarre astrocytes and accumulation of numerous foamy macrophages (gitter cells). Immunohistochemical investigation of reactive astrocytes revealed several different cytoplasmic proteins. Conclusion This is the first reported case of large felid leucoencephalomyelopathy in Australia.

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Section: Discussionmentioning

confidence: 97%

Large felid leucoencephalomyelopathy in a Sumatran tiger (Panthera tigris sumatrae) from an Australian zoo

Hanshaw¹,

McLelland

Manavis

et al. 2019

Aust Veterinary J

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“…IL‐17 activates and enhances the release of chemokine and pro‐inflammatory cytokines in astrocytes, which promotes the migration of CCR6 + Th17 cells to the site of inflammation (Liu et al, ; Meares, Ma, Qin, & Benveniste, ). Moreover, the presence of reactive astrocytes and axonal damage is an early event during multiple sclerosis lesion formation and lead to astrocyte immune responses (Brosnan & Raine, ; Ponath et al, ). These discoveries provide important insights into the astrocytes and Th17/IL‐17 that regulate inflammation and MS progression.…”

Section: Introductionmentioning

confidence: 99%

MiR‐409‐3p and MiR‐1896 co‐operatively participate in IL‐17‐induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling

Liu

Feng

Yang

et al. 2018

Glia

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Th17 cells and interleukin‐17 (IL‐17) have been found to play an important role in the pathology of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Response to IL‐17, reactive astrocytes accompany with immune cells infiltration and axonal damage in MS/EAE. However, the role and the regulatory mechanism of IL‐17‐activated astrocytes in inflammation and in the EAE process still remain largely unknown. Here, we elucidated that miR‐409‐3p and miR‐1896, as co‐upregulated microRNAs in activated astrocytes and in EAE mice, targeted suppressor of cytokine signaling proteins 3 (SOCS3). Overexpression of miR‐409‐3p or miR‐1896 significantly reduced SOCS3 expression and increased phosphorylation of STAT3 as well as induced the inflammatory cytokines production (IL‐1β, IL‐6, IP‐10, MCP‐1, and KC), CD4+T cells migration and demyelination, in turn aggravating EAE development. Importantly, the effects of co‐overexpression of miR‐409‐3p and miR‐1896 in vitro or in vivo are strongly co‐operative. In contrast, simultaneously silenced miR‐409‐3p and miR‐1896 co‐operatively ameliorates inflammation and demyelination in the central nervous system of EAE mice. Collectively, our findings highlight that miR‐409‐3p and miR‐1896 co‐ordinately promote the production of inflammatory cytokines in reactive astrocytes through the SOCS3/STAT3 pathway and enhance reactive astrocyte‐directed chemotaxis of CD4+T cells, leading to aggravate pathogenesis in EAE mice. Co‐inhibition of miR‐409‐3p and miR‐1896 may be a therapeutic target for treating MS and neuroinflammation.

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“…; Ponath et al . ). In addition, other authors have observed internalization of dendrimeric nanoparticles by astrocytes (Salgado et al .…”

Section: Discussionmentioning

confidence: 97%

G5G2.5 core‐shell tecto‐dendrimer specifically targets reactive glia in brain ischemia

Murta

Schilrreff

Rosciszewski

et al. 2018

Journal of Neurochemistry

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Secondary neuronal death is a serious stroke complication. This process is facilitated by the conversion of glial cells to the reactive pro-inflammatory phenotype that induces neurodegeneration. Therefore, regulation of glial activation is a compelling strategy to reduce brain damage after stroke. However, drugs have difficulties to access the CNS, and to specifically target glial cells. In the present work, we explored the use core-shell polyamidoamine tecto-dendrimer (G5G2.5 PAMAM) and studied its ability to target distinct populations of stroke-activated glial cells. We found that G5G2.5 tecto-dendrimer is actively engulfed by primary glial cells in a time- and dose-dependent manner showing high cellular selectivity and lysosomal localization. In addition, oxygen-glucose deprivation or lipopolysaccharides exposure in vitro and brain ischemia in vivo increase glial G5G2.5 uptake; not being incorporated by neurons or other cell types. We conclude that G5G2.5 tecto-dendrimer is a highly suitable carrier for targeted drug delivery to reactive glial cells in vitro and in vivo after brain ischemia.

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Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology

Cited by 172 publications

References 38 publications

Large felid leucoencephalomyelopathy in a Sumatran tiger (Panthera tigris sumatrae) from an Australian zoo

Large felid leucoencephalomyelopathy in a Sumatran tiger (Panthera tigris sumatrae) from an Australian zoo

MiR‐409‐3p and MiR‐1896 co‐operatively participate in IL‐17‐induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling

G5G2.5 core‐shell tecto‐dendrimer specifically targets reactive glia in brain ischemia

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