Myelin is an essential structure that facilitates rapid saltatory conduction in the nervous system. Discrepancies in myelin microstructure are a hallmark of numerous neurological disorders, rendering the assessment of myelin integrity and content an indispensable tool in clinical diagnostics and neuroscience research. Extensive research has been dedicated to scrutinizing its biochemical makeup and morphology under normal, pathological, and experimental conditions over the years. In this review, we present an updated summary of the myelin sheath's structure, composition, and developmental trajectory. We systematically enumerate and contrast eight prevalent myelin staining techniques across dimensions of sensitivity, specificity, and resolution, delving into their underlying staining principles. With an initial application of myelin histology on the mouse demyelination model, our review accentuates the accurate delineation of myelination and the microstructural analysis of the myelin sheath. Such insights are anticipated to significantly contribute to the evaluation and understanding of white matter pathologies.
Myelin Sheath/metabolism* ; Animals ; Humans ; Demyelinating Diseases/pathology* ; Staining and Labeling/methods*

Glial cells in the central nervous system (CNS) are composed of oligodendrocytes, astrocytes and microglia. They contribute more than half of the total cells of the CNS, and are essential for neural development and functioning. Studies on the fate specification, differentiation, and functional diversification of glial cells mainly rely on the proper use of cell- or stage-specific molecular markers. However, as cellular markers often exhibit different specificity and sensitivity, careful consideration must be given prior to their application to avoid possible confusion. Here, we provide an updated overview of a list of well-established immunological markers for the labeling of central glia, and discuss the cell-type specificity and stage dependency of their expression.
Neuroglia/metabolism* ; Central Nervous System ; Oligodendroglia/metabolism* ; Astrocytes/metabolism* ; Microglia

Animals ; Ctenophora ; Nervous System ; Neurons

Humans ; Neuroinflammatory Diseases ; COVID-19/complications* ; Brain

Noxious mechanical information is transmitted through molecularly distinct nociceptors, with pinprick-evoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2 (Npy2r) and von Frey filament-evoked punctate pressure information via unmyelinated C fiber nociceptors marked by MrgprD. However, the molecular programs controlling their development are only beginning to be understood. Here we demonstrate that Npy2r-expressing sensory neurons are in fact divided into two groups, based on transient or persistent Npy2r expression. Npy2r-transient neurons are myelinated, likely including A-fiber nociceptors, whereas Npy2r-persistent ones belong to unmyelinated pruriceptors that co-express Nppb. We then showed that the transcription factors NFIA and Runx1 are necessary for the development of Npy2r-transient A-fiber nociceptors and MrgprD C-fiber nociceptors, respectively. Behaviorally, mice with conditional knockout of Nfia, but not Runx1 showed a marked attenuation of pinprick-evoked nocifensive responses. Our studies therefore identify a transcription factor controlling the development of myelinated nociceptors.

Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYK-deficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.
Animals ; Animals, Newborn ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; Cell Differentiation ; drug effects ; physiology ; Cell Proliferation ; drug effects ; genetics ; Cells, Cultured ; Cuprizone ; toxicity ; Demyelinating Diseases ; chemically induced ; metabolism ; pathology ; Embryo, Mammalian ; Gene Expression Regulation, Developmental ; genetics ; Ki-67 Antigen ; metabolism ; Mice ; Mice, Inbred C57BL ; Myelin Basic Protein ; metabolism ; Myelin Proteolipid Protein ; metabolism ; Myelin Sheath ; drug effects ; metabolism ; Oligodendroglia ; drug effects ; metabolism ; Protein-Tyrosine Kinases ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley