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NG2‐glia are an abundant population of cells in the adult CNS that make up a novel glial cell type. Here, we have examined calcium signals in NG2‐glia identified by expression of the fluorescent protein DsRed under the control of the NG2 promoter in the white matter of the mouse optic nerve. We focused on mice aged postnatal day (P)12–16, after the main period of oligodendrocyte generation. Using...
The initial interaction between the Schwann cell and the axon is a complex and poorly understood aspect of the myelination process. To investigate the molecular mechanisms involved in this interaction and to identify novel genes required for myelination, we performed an RNA profiling analysis, comparing Schwann cells cultured alone or in the presence of neurons. This led to the selection of 30 genes,...
In the peripheral nervous system, Schwann cells (SCs) promote nerve regeneration by the secretion of trophic support molecules and the establishment of a supportive growth matrix. Elucidating factors that promote SC outgrowth following nerve injury is an important strategy for improving nerve regeneration. We identified the Netrin‐1 receptors, Deleted in Colorectal Cancer (DCC) and Uncoordinated (Unc)5H2...
Olfactory ensheathing cells (OECs) support the regeneration of olfactory sensory neurons throughout life, however, it remains unclear how OECs respond to a major injury. We have examined the proliferation and migration of OECs following unilateral bulbectomy in postnatal mice. S100ß‐DsRed and OMP‐ZsGreen transgenic mice were used to visualize OECs and olfactory neurons, respectively, and we used the...
Myelin sheath thickness is precisely adjusted to axon caliber, and in the peripheral nervous system, neuregulin 1 (NRG1) type III is a key regulator of this process. It has been proposed that the protease BACE1 activates NRG1 dependent myelination. Here, we characterize the predicted product of BACE1‐mediated NRG1 type III processing in transgenic mice. Neuronal overexpression of a NRG1 type III‐variant,...
Uptake of K+ released by axons during action potential propagation is a major function of astrocytes. Here, we demonstrate the importance of glial inward rectifying potassium channels (Kir) in regulating extracellular K+ ([K+]o) and axonal electrical activity in CNS white matter of the mouse optic nerve. Increasing optic nerve stimulation frequency from 1 Hz to 10–35 Hz for 120 s resulted in a rise...
In the mammalian brain, the subcortical white matter comprises long‐range axonal projections and their associated glial cells. Here, astrocytes and oligodendrocytes serve specific functions during development and throughout adult life, when they meet the metabolic needs of long fiber tracts. Within a short period of time, oligodendrocytes generate large amount of lipids, such as cholesterol, and membrane...
Ischemic pathologies of white matter (WM) include a large proportion of stroke and developmental lesions while multiple sclerosis (MS) is the archetype nonischemic pathology. Growing evidence suggests other important diseases including neurodegenerative and psychiatric disorders also involve a significant WM component. Axonal, oligodendroglial, and astroglial damage proceed via distinct mechanisms...
White matter (WM) tracts are bundles of myelinated axons that provide for rapid communication throughout the CNS and integration in grey matter (GM). The main cells in myelinated tracts are oligodendrocytes and astrocytes, with small populations of microglia and oligodendrocyte precursor cells. The prominence of neurotransmitter signaling in WM, which largely exclude neuronal cell bodies, indicates...
The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when proteolipid protein (PLP) replaced P0 protein as the most abundant protein of CNS myelin. However, PLP did not replace P0 in peripheral nervous system (PNS) myelin. To investigate the possible consequences of a PLP to P0 shift in PNS myelin, we engineered mice to express PLP instead of P0 in PNS...
Early white matter (WM) changes are common in dementia and may contribute to functional decline. We here examine this phenomenon in an induced dementia model for the first time. We report a novel and selective form of myelin injury as the first manifestation of tauopathy in the adult central nervous system. Myelin pathology rapidly followed the induction of a P301 tau mutation associated with fronto‐temporal...
Early views of glia as relatively inert, housekeeping cells have evolved, and glia are now recognized as dynamic cells that not only respond to neuronal activity but also sense metabolic changes and regulate neuronal metabolism. This evolution has been aided in part by technical advances permitting progressively better spatial and temporal resolution. Recent advances in cell‐type specific genetic...
Axonal mRNA transport and local protein synthesis are crucial for peripheral axon regeneration. To date, it remains unclear how ribosomes localize to axons. They may be co‐transported with mRNAs or, as suggested by recent studies, transferred from Schwann cells (SC). Here, we generated transgenic “RiboTracker” mice expressing tdTomato‐tagged ribosomal protein L4 in specific cell types when crossed...
The transition of differentiated Schwann cells to support of nerve repair after injury is accompanied by remodeling of the Schwann cell epigenome. The EED‐containing polycomb repressive complex 2 (PRC2) catalyzes histone H3K27 methylation and represses key nerve repair genes such as Shh, Gdnf, and Bdnf, and their activation is accompanied by loss of H3K27 methylation. Analysis of nerve injury in mice...
Interactions between axons and Schwann cells are essential for the acquisition of Schwann cell radial and longitudinal polarity and myelin sheath assembly. In the internode, the largest of these longitudinal domains, axon‐Schwann cell interactions are mediated by the Nectin‐like (Necl) cell adhesion proteins, also known as SynCAMs or Cadms. In particular, Necl‐1/Cadm3 expressed on the axon surface...
Type I interferons (IFN‐I) are the principal antiviral molecules of the innate immune system and can be made by most cell types, including central nervous system cells. IFN‐I has been implicated in neuroinflammation during neurodegeneration, but its mechanism of induction and its consequences remain unclear. In the current study, we assessed expression of IFN‐I in murine prion disease (ME7) and examined...
Single oligodendrocytes produce myelin sheaths around multiple axons in the central nervous system. Interfascicular oligodendrocytes (IOs) facilitate nerve conduction, but their detailed morphologies remain largely unknown. In the present study, we three‐dimensionally reconstructed IOs in the corpus callosum of adult mouse using serial block face scanning electron microscopy. The cell bodies of IOs...
Elovl5 elongates fatty acids with 18 carbon atoms and in cooperation with other enzymes guarantees the normal levels of very long‐chain fatty acids, which are necessary for a proper membrane structure. Action potential conduction along myelinated axons depends on structural integrity of myelin, which is maintained by a correct amount of fatty acids and a proper interaction between fatty acids and...
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