During Development NG2 Glial Cells of the Spinal Cord are Restricted to the Oligodendrocyte Lineage, but Generate Astrocytes upon Acute Injury

Huang, Wenhui; Bai, Xianshu; Stopper, Laura; Cãtãlin, Bogdan; Cartarozzi, Luciana Politti; Scheller, Anja; Kirchhoff, Frank

doi:10.1016/j.neuroscience.2018.06.015

Cited by 32 publications

(33 citation statements)

References 33 publications

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“…For OPC culture, cells were dissociated from the cortex of neonatal mice post 2 to 3 days, as previous described [ 34 , 87 ]. At this age and tissue region, isolated OPCs generate more than 90% of the WM OLs in the CNS [ 88 ]. Briefly, the cells were maintained in a mixed glial culture medium in poly- d -lysine-coated 75-cm 2 flasks at 37 °C/5% CO 2 for 9 days.…”

Section: Methodsmentioning

confidence: 99%

ABCA1/ApoE/HDL Signaling Pathway Facilitates Myelination and Oligodendrogenesis after Stroke

Zacharek

et al. 2020

IJMS

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ATP-binding cassette transporter A1 (ABCA1) plays an important role in the regulation of apolipoprotein E (ApoE) and the biogenesis of high-density lipoprotein (HDL) cholesterol in the mammalian brain. Cholesterol is a major source for myelination. Here, we investigate whether ABCA1/ApoE/HDL contribute to myelin repair and oligodendrogenesis in the ischemic brain after stroke. Specific brain ABCA1-deficient (ABCA1-B/-B) and ABCA1-floxed (ABCA1fl/fl) control mice were subjected to permanent distal middle-cerebral-artery occlusion (dMCAo) and were intracerebrally administered (1) artificial mouse cerebrospinal fluid (CSF) as vehicle control, (2) human plasma HDL3, and (3) recombined human ApoE2 starting 24 h after dMCAo for 14 days. All stroke mice were sacrificed 21 days after dMCAo. The ABCA1-B/-B–dMCAo mice exhibit significantly reduced myelination and oligodendrogenesis in the ischemic brain as well as decreased functional outcome 21 days after stroke compared with ABCA1fl/fl mice; administration of human ApoE2 or HDL3 in the ischemic brain significantly attenuates the deficits in myelination and oligodendrogenesis in ABCA1-B/-B–dMCAo mice ( p < 0.05, n = 9/group). In vitro, ABCA1-B/-B reduces ApoE expression and decreases primary oligodendrocyte progenitor cell (OPC) migration and oligodendrocyte maturation; HDL3 and ApoE2 treatment significantly reverses ABCA1-B/-B-induced reduction in OPC migration and oligodendrocyte maturation. Our data indicate that the ABCA1/ApoE/HDL signaling pathway contributes to myelination and oligodendrogenesis in the ischemic brain after stroke.

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Section: Methodsmentioning

confidence: 99%

ABCA1/ApoE/HDL Signaling Pathway Facilitates Myelination and Oligodendrogenesis after Stroke

Zacharek

et al. 2020

IJMS

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“…In the postnatal CNS, all OPCs express NG2, therefore they are also termed NG2 glia [ 23 , 42 , 49 ]. Numerous studies using antibody immunostaining and transgenic mouse models revealed that in the healthy CNS, the expression of NG2 is restricted to OPCs and pericytes but cannot be detected in microglia or astrocytes [ 10 , 11 , 22 – 24 , 28 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

Acute brain injuries trigger microglia as an additional source of the proteoglycan NG2

Huang

Bai

Meyer

et al. 2020

acta neuropathol commun

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NG2 is a type I transmembrane glycoprotein known as chondroitin sulfate proteoglycan 4 (CSPG4). In the healthy central nervous system, NG2 is exclusively expressed by oligodendrocyte progenitor cells and by vasculature pericytes. A large body of immunohistochemical studies showed that under pathological conditions such as acute brain injuries and experimental autoimmune encephalomyelitis (EAE), a number of activated microglia were NG2 immuno-positive, suggesting NG2 expression in these cells. Alternative explanations for the microglial NG2 labeling consider the biochemical properties of NG2 or the phagocytic activity of activated microglia. Reportedly, the transmembrane NG2 proteoglycan can be cleaved by a variety of proteases to deposit the NG2 ectodomain into the extracellular matrix. The ectodomain, however, could also stick to the microglial surface. Since microglia are phagocytic cells engulfing debris of dying cells, it is difficult to identify a genuine expression of NG2. Recent studies showing (1) pericytes giving rise to microglial after stroke, and (2) immune cells of NG2-EYFP knock-in mice lacking NG2 expression in an EAE model generated doubts for the de novo expression of NG2 in microglia after acute brain injuries. In the current study, we took advantage of three knock-in mouse lines (NG2-CreERT2, CX 3 CR 1 -EGFP and NG2-EYFP) to study NG2 expression indicated by transgenic fluorescent proteins in microglia after tMCAO (transient middle cerebral artery occlusion) or cortical stab wound injury (SWI). We provide strong evidence that NG2-expressing cells, including OPCs and pericytes, did not differentiate into microglia after acute brain injuries, whereas activated microglia did express NG2 in a disease-dependent manner. A subset of microglia continuously activated the NG2 gene at least within the first week after tMCAO, whereas within 3 days after SWI a limited number of microglia at the lesion site transiently expressed NG2. Immunohistochemical studies demonstrated that these microglia with NG2 gene activity also synthesized the NG2 protein, suggesting activated microglia as an additional source of the NG2 proteoglycan after acute brain injuries. Electronic supplementary material The online version of this article (10.1186/s40478-020-01016-2) contains supplementary material, which is available to authorized users.

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“…In cases of substantial tissue disruption, OPCs could be an additional source of astrocytes to further supplement their numbers. There has been some debate about the capacity of OPCs to differentiate into astrocytes following SCI, but two groups have recently provided compelling evidence they do so using genetic fate mapping approaches (Hackett et al, ; Huang et al, ). Attenuating the OPC response to injury also diminishes astrogliosis, suggesting a correlative relationship between these processes (Hesp et al, ; Rodriguez et al, ).…”

Section: Introductionmentioning

confidence: 99%

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

Duncan

Manesh

Hilton

et al. 2019

Glia

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Oligodendrocyte progenitor cells (OPCs) are the most proliferative and dispersed population of progenitor cells in the adult central nervous system, which allows these cells to rapidly respond to damage. Oligodendrocytes and myelin are lost after traumatic spinal cord injury (SCI), compromising efficient conduction and, potentially, the long‐term health of axons. In response, OPCs proliferate and then differentiate into new oligodendrocytes and Schwann cells to remyelinate axons. This culminates in highly efficient remyelination following experimental SCI in which nearly all intact demyelinated axons are remyelinated in rodent models. However, myelin regeneration comprises only one role of OPCs following SCI. OPCs contribute to scar formation after SCI and restrict the regeneration of injured axons. Moreover, OPCs alter their gene expression following demyelination, express cytokines and perpetuate the immune response. Here, we review the functional contribution of myelin regeneration and other recently uncovered roles of OPCs and their progeny to repair following SCI.

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During Development NG2 Glial Cells of the Spinal Cord are Restricted to the Oligodendrocyte Lineage, but Generate Astrocytes upon Acute Injury

Cited by 32 publications

References 33 publications

ABCA1/ApoE/HDL Signaling Pathway Facilitates Myelination and Oligodendrogenesis after Stroke

ABCA1/ApoE/HDL Signaling Pathway Facilitates Myelination and Oligodendrogenesis after Stroke

Acute brain injuries trigger microglia as an additional source of the proteoglycan NG2

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

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