NG2-Glia, a New Player in Energy Balance

Robins, Sarah C.; Kokoeva, Maia V.

doi:10.1159/000488111

Cited by 11 publications

(7 citation statements)

References 59 publications

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“…These cells, which had previously only been regarded as oligodendrocyte precursors, constitute the fourth large population of glia in addition to microglia, astrocytes, and oligodendrocytes [ 12 ]. The NG2 glia is believed to play an important role in the maintenance of microglial homeostasis [ 14 , 15 ], to influence the neuronal/microglial interactions [ 15 ], and to participate in energy balance via leptin-sensing neurons [ 13 ]. Regarding the latter function, the role of leptin as an nNOS suppressing agent is of interest [ 111 ], as this concerns a function shared by melatonin and its metabolite AMK ( N 1 -acetyl-5-methoxykynuramine) [ 16 , 17 , 18 , 19 , 91 ].…”

Section: Melatonin Influences Glial and Glial-neuronal Interactionsmentioning

confidence: 99%

“…Finally, the biology of microglia requires the consideration of a further glia type, the NG2 glia, a term coined according to the presence of nerve/glial antigen 2 (=Neural-Glial 2). These cells, also known as polydendrocytes, which were previously thought to only represent oligodendrocyte precursors, are actually regarded as a fourth category of glia [ 12 , 13 ], with specific functions in the regulation of microglia [ 14 , 15 , 16 ]. Generally, the functions of microglia cannot be sufficiently understood without considering their interactions with other cell types.…”

Section: Introductionmentioning

confidence: 99%

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Melatonin and Microglia

Hardeland

2021

IJMS

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Melatonin interacts in multiple ways with microglia, both directly and, via routes of crosstalk with astrocytes and neurons, indirectly. These effects of melatonin are of relevance in terms of antioxidative protection, not only concerning free-radical detoxification, but also in prevention of processes that cause, promote, or propagate oxidative stress and neurodegeneration, such as overexcitation, toxicological insults, viral and bacterial infections, and sterile inflammation of different grades. The immunological interplay in the CNS, with microglia playing a central role, is of high complexity and includes signaling toward endothelial cells and other leukocytes by cytokines, chemokines, nitric oxide, and eikosanoids. Melatonin interferes with these processes in multiple signaling routes and steps. In addition to canonical signal transduction by MT1 and MT2 melatonin receptors, secondary and tertiary signaling is of relevance and has to be considered, e.g., via the upregulation of sirtuins and the modulation of pro- and anti-inflammatory microRNAs. Many details concerning the modulation of macrophage functionality by melatonin are obviously also applicable to microglial cells. Of particular interest is the polarization toward M2 subtypes instead of M1, i.e., in favor of being anti-inflammatory at the expense of proinflammatory activities, which is well-documented in macrophages but also applies to microglia.

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Section: Melatonin Influences Glial and Glial-neuronal Interactionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Melatonin and Microglia

Hardeland

2021

IJMS

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“…NG2‐glia could be novel therapeutic targets in cerebrovascular disorders, especially in the context of vascular cognitive dysfunction in an aging CNS 124 . NG2‐glia also have an important role to maintain energy homeostasis 125 . In addition, NG2‐glia can mediate neuroinflammation through TGF‐β2‐TGF‐β type II receptor‐CX3C chemokine receptor 1 signaling to inhibit microglia activation 117 .…”

Section: Discussionmentioning

confidence: 99%

NG2‐glia crosstalk with microglia in health and disease

Zuo

Zhou

et al. 2022

CNS Neurosci Ther

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Glia are non-neuronal cells, also called neuroglia. 1 Glia exist within the mammalian nervous system to provide several essential functions for neurons, such as maintaining homeostasis, support, protection, and generating myelin. 2,3 Traditionally, astrocytes, microglia, and oligodendrocytes are the three major classes of glia. In the last two decades, neuron glia antigen-2 (NG2) glial cell has been considered as the fourth type of glial cell in the central nervous system (CNS). 4 NG2-glia are also called oligodendrocyte precursor cells 5 and express NG2. [6][7][8] NG2 is a chondroitin sulphate proteoglycan 4 (CSPG4), which is also expressed on infiltrating macrophages and activated microglia in various CNS insults. 9-11 NG2, together with platelet-derived growth factor receptor alpha (PDGFRα), is a marker of NG2-glia. 12,13 NG2-glia account for 5%-10% of all cells in the adult CNS. 14 NG2-glia are extremely heterogeneous with different characteristics and functions. 15,16 NG2-glia are widely scattered in the CNS in late development and throughout adulthood. NG2-glia may differentiate into neurons or astrocytes under diverse conditions, such as at embryonic stages, and under forced expression of neurogenic factors. [17][18][19] Early postnatal NG2-glia can become multipotent neurospheres and quickly differentiate into neurons, astrocytes, and oligodendrocytes in vitro. 18 More than one-third of the protoplasmic astrocytes are differentiated from NG2-glia in ventral forebrain when NG2-Cre is prenatally triggered in NG2-glia before embryonic day 17.5. 20 A single homeodomain transcription factor Dlx2-transfects NG2-glia differentiated into GABAergic inhibitory neurons. 19 Adult NG2-glia also differentiate into neurons in the cortical gray matter. 21 The anti-epileptic epigenetic regulator valproic

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“…Another investigation that focused on damage of white matter after focal cerebral ischemia described beneficial effects of melatonin, which comprised upregulation of NG2 (Neural-Glial 2) [151], a marker of NG2 glia, which had previously only been regarded as so-called polydendrocytes, i.e., oligodendrocyte precursors. However, the actual view is that of a fourth category of glia, termed NG2 glia, which has specific functions in the regulation of microglial activities [93,94,152,153]. With regard to the profound roles of microglia in both inflammatory insults and protection within the CNS as well as the influence of melatonin in maintaining the balance of microglial polarization and activities [59], the role of NG2 should come into the focus of melatonin research.…”

Section: Ng2 Glia and Oligodendrocytes A Field Of Future Perspectivesmentioning

confidence: 99%

Melatonin and the Programming of Stem Cells

Hardeland

2022

IJMS

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Melatonin interacts with various types of stem cells, in multiple ways that comprise stimulation of proliferation, maintenance of stemness and self-renewal, protection of survival, and programming toward functionally different cell lineages. These various properties are frequently intertwined but may not be always jointly present. Melatonin typically stimulates proliferation and transition to the mature cell type. For all sufficiently studied stem or progenitor cells, melatonin’s signaling pathways leading to expression of respective morphogenetic factors are discussed. The focus of this article will be laid on the aspect of programming, particularly in pluripotent cells. This is especially but not exclusively the case in neural stem cells (NSCs) and mesenchymal stem cells (MSCs). Concerning developmental bifurcations, decisions are not exclusively made by melatonin alone. In MSCs, melatonin promotes adipogenesis in a Wnt (Wingless-Integration-1)-independent mode, but chondrogenesis and osteogenesis Wnt-dependently. Melatonin upregulates Wnt, but not in the adipogenic lineage. This decision seems to depend on microenvironment and epigenetic memory. The decision for chondrogenesis instead of osteogenesis, both being Wnt-dependent, seems to involve fibroblast growth factor receptor 3. Stem cell-specific differences in melatonin and Wnt receptors, and contributions of transcription factors and noncoding RNAs are outlined, as well as possibilities and the medical importance of re-programming for transdifferentiation.

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NG2-Glia, a New Player in Energy Balance

Cited by 11 publications

References 59 publications

Melatonin and Microglia

Melatonin and Microglia

NG2‐glia crosstalk with microglia in health and disease

Melatonin and the Programming of Stem Cells

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