NG2‐glia crosstalk with microglia in health and disease

Abstract

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

Oligodendrocyte Progenitors in Schizophrenia: The Role in Pathogenesis and Potential Treatment Target

“…Ключевым фактором воспаления в мозге является микроглия, которая представляет собой резидентные макрофаги мозга миелоидного происхождения [72]. В физиологических условиях микроглия обладает рамифицированной формой с многочисленными тонкими отростками.…”

“…Известно, что баланс между провоспалительным (М1) и противовоспалительным (М2) фенотипом микроглии в мозге тесно связан с характеристиками олигодендрогенеза и миелинизации/ремиелинизации [84]. Так, М2-микроглия способна стимулировать ремиелинизацию мозга и восстановление нарушенных когнитивных функций у мышей, подвергнутых ишемии мозга, за счет стимуляции пролиферации и дифференцировки ОП [72,85]. У мышей, генетически лишенных М2-микроглии, экспериментальный аутоиммунный энцефалит (ЭАЭ) сопровождался значительно более выраженными нарушениями дифференцировки ОП, чем у обычных животных [86].…”

“…Показано, что супернатант М2-микроглии (активация фумаровой кислотой) способен стимулировать пролиферацию ОП [87], тогда как супернатант М1-клеток (активация липосахаридом) ее подавлял [88]. Воздействие M2-супернатанта оказывало также выраженный стимулирующий на дифференцировку ОП, тогда как М1-микроглия подавляла созревание ОП [72].…”

CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity

“…OPC surface‐bound NG2 PG binds platelet‐derived growth factor (PDGF)‐AA and enhances PDGF receptor alpha (PDGFRα) activation and signaling. A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) is also highly upregulated in OPCs (Jiang et al., 2023) and releases NG2 ectodomain, this accelerates oligodendrocyte differentiation and attenuates PDGFRα signaling improving remyelination of damaged axons (Zhang et al., 2022). The released OPC NG2 ectodomains may adhere to glial cells during acute brain injuries and may along with endogenous NG2 PG participate in tissue repair (Huang et al., 2020).…”

CRTC1 is a potential target to delay aging-induced cognitive deficit by protecting the integrity of the blood-brain barrier via inhibiting inflammation

“…Abnormal activation of microglia during CNS injury is involved in the development and progression of neurodegenerative diseases. 51 Notably, the ketogenic diet improves cognitive function in AD by inhibiting microglia activation and neuroinflammation. 52 Aging can shift microglia morphology and microglia lost the ability to regulate the migration and clearance function, as well as the ability to shift from a pro-inflammatory to an anti-inflammatory status to modulate injury and repair.…”