Calcium Signaling in the Oligodendrocyte Lineage: Regulators and Consequences

2020 ◽  
Vol 43 (1) ◽  
pp. 163-186 ◽  
Author(s):  
Pablo M. Paez ◽  
David A. Lyons

Cells of the oligodendrocyte lineage express a wide range of Ca2+ channels and receptors that regulate oligodendrocyte progenitor cell (OPC) and oligodendrocyte formation and function. Here we define those key channels and receptors that regulate Ca2+ signaling and OPC development and myelination. We then discuss how the regulation of intracellular Ca2+ in turn affects OPC and oligodendrocyte biology in the healthy nervous system and under pathological conditions. Activation of Ca2+ channels and receptors in OPCs and oligodendrocytes by neurotransmitters converges on regulating intracellular Ca2+, making Ca2+ signaling a central candidate mediator of activity-driven myelination. Indeed, recent evidence indicates that localized changes in Ca2+ in oligodendrocytes can regulate the formation and remodeling of myelin sheaths and perhaps additional functions of oligodendrocytes and OPCs. Thus, decoding how OPCs and myelinating oligodendrocytes integrate and process Ca2+ signals will be important to fully understand central nervous system formation, health, and function.

2015 ◽  
Vol 9s2 ◽  
pp. JEN.S25480 ◽  
Author(s):  
Ana Ana Maria ◽  
Moreno-Ramos Oscar Andréas ◽  
Neena B. Haider

The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration.


2019 ◽  
Author(s):  
Benjamin V Ineichen ◽  
Keying Zhu ◽  
Karl E Carlström

AbstractIn the central nervous system (CNS), axons and its surrounding myelin sheaths, generated by oligodendrocytes, greatly depend on each other, where oligodendrocytes provide axons with both trophic and metabolic support. Across spices, assessment of the axon-myelin ultrastructure is the key-approach to visualize de- and re-myelination of axons. However, this assessment omits to provide information on axonal homeostasis or how axon-myelin influence one another. Since mitochondria may adjust in size thus mirroring the intracellular physiological and metabolic status we applied this to myelinated axons in the CNS. We herein show that a large axonal mitochondria diameter correlates with thinner surrounding myelin sheaths across different CNS tracts and species, including human. We also show that the relation between axonal mitochondria diameter and surrounding myelin thickness is a valuable measurement to verify advanced remyelination in two commonly used experimental demyelinating models, namely the cuprizone and the lysolecithin (LPC) model. Lastly, we show that axonal mitochondria adjust in diameter in response to the thickness of the axonal surrounding myelin whereas the opposite adaption was absent. In summary, the link between axonal mitochondria diameter and surrounding myelin thickness provide insight on the axon-myelin relation both during homeostasis and pathological conditions. This link is also translational applicable and can thus contribute to a better understanding on how to study remyelination using experimental models.


2019 ◽  
Vol 72 (8) ◽  
pp. 1437-1441
Author(s):  
Pavel Dyachenko ◽  
Igor Filchakov ◽  
Anatoly Dyachenko ◽  
Victoria Kurhanskaya

Introduction: Viral encephalitis accounts for 40-70% of all cases worldwide, central nervous system infections pose a diagnostic challenge because clinical manifestations are not typically pathognomonic for specific pathogens, and a wide range of agents can be causative. The aim: To assess the diagnostic value of intrathecal synthesis of specific antibodies in patients with inflammatory lesions of the central nervous system. Materials and methods: Within the framework of the study, two groups of 90 people in each were formed from the patients with neuroinfections admitted to our Center. Intrathecal synthesis (ITS) of total (unspecific) IgG in members of one of group (group of compare) was determined. Brain synthesis of specific antibodies (Ab) to some neurotropic pathogens (herpes simplex virus 1/2, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, rubella virus, Borrelies) was studied in the second group of patients (group of interest). There were no statistically significant differences between groups by gender and age. Encephalitis and encephalomyelitis prevailed among patients of both groups Results: ITS of total IgG was established in 30 (33.3 ± 6.1 %) patients of the first group with IgG index more than 0.6 indicating on inflammatory process in CNS and no marked changes of CSF. ITS of specific Ab was determined in 23 of 90 (25.6 ± 4.6 %) patients included into group of interest. In more than half of cases Ab to several infectious agents were detected simultaneously. ITS of various specificity, in particular, to measles and rubella viruses, and VZV, known as MRZ-reaction, is characteristic of some autoimmune lesions of CNS, multiple sclerosis first of all. In fact, further research of 5 patients with MRZ-reaction confirmed their autoimmune failure of CNS. Detection of ITS in the CSF samples didn’t depend on concentration of specific Ab in serum and CSF and wasn’t followed by HEB dysfunctions which were observed with the same frequency in patients with or without ITS (13.0 % and 13.6 % respectively). Conclusion: Specific Ab synthesis to several neurotropic pathogens in the CSF of significant part of examined patients was established. Thus, diagnostic value of ITS of specific immunoglobulins seems to be limited to cases in which autoimmune damage of the CNS is suspected.


1996 ◽  
Vol 54 (2) ◽  
pp. 331-334 ◽  
Author(s):  
L. A. V Peireira ◽  
M. A. Cruz-Höfling ◽  
M. S. J. Dertkigil ◽  
D. L. Graça

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.


Glia ◽  
2018 ◽  
Vol 67 (5) ◽  
pp. 857-869 ◽  
Author(s):  
Dylan A. Galloway ◽  
Stephanie N. Blandford ◽  
Tangyne Berry ◽  
John B. Williams ◽  
Mark Stefanelli ◽  
...  

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Peter A. Walker ◽  
Matthew T. Harting ◽  
Shinil K. Shah ◽  
Mary-Clare Day ◽  
Ramy El Khoury ◽  
...  

Recent preclinical work investigating the role of progenitor cell therapies for central nervous system (CNS) injuries has shown potential neuroprotection in the setting of traumatic brain injury (TBI), spinal cord injury (SCI), and ischemic stroke. Mechanisms currently under investigation include engraftment and transdifferentiation, modulation of the locoregional inflammatory milieu, and modulation of the systemic immunologic/inflammatory response. While the exact mechanism of action remains controversial, the growing amount of preclinical data demonstrating the potential benefit associated with progenitor cell therapy for neurological injury warrants the development of well-controlled clinical trials to investigate therapeutic safety and efficacy. In this paper, we review the currently active or recently completed clinical trials investigating the safety and potential efficacy of bone marrow-derived progenitor cell therapies for the treatment of TBI, SCI, and ischemic stroke. Our review of the literature shows that while the preliminary clinical trials reviewed in this paper offer novel data supporting the potential efficacy of stem/progenitor cell therapies for CNS injury, a great deal of additional work is needed to ensure the safety, efficacy, and mechanisms of progenitor cell therapy prior to widespread clinical trials.


2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Joanna Rosińczuk ◽  
Robert Dymarek ◽  
Ireneusz Całkosiński

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on central nervous system consists of changing expression of estrogen receptors, whereas the result of chronic inflammatory reaction caused by dioxin is occurrence of destructive changes in various organs connected with disturbed metabolism of connective tissue and damage of cells. The aim of the study was to determine the effect of dioxins on function, ultrastructure, and cytological and histological structure of hippocampus, particularly on expression of estrogen receptors in central nervous system as well as to define protective influence of tocopherol (TCP) and acetylsalicylic acid (ASA) on the decrease in activity of proinflammatory effects in central nervous system. It was shown that TCDD contributes to destructive and inflammatory changes along with demyelization of myelin sheaths and atrophy of estrogen receptors in hippocampus. Dioxin contributes to atrophy of estrogen receptors in hippocampus, in which also destructive and inflammatory changes were found along with demyelination of myelin sheaths. Histopathological and ultrastructural image of hippocampus areas in rats, in which both TCP and ASA were used, is characterized by poorly expressed degenerative changes and smaller inflammatory reactivity. Using both TCP and ASA has a protective effect on functions of central nervous system.


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