In the central nervous system (CNS) of most vertebrates, oligodendrocytes enwrap neuronal axons with extensions of their plasma membrane to form the myelin sheath. Several proteins are characteristically found in myelin of which myelin basic protein (MBP) is the second most abundant one after proteolipid protein. The lack of functional MBP in rodents results in a severe hypomyelinated phenotype in the CNS demonstrating its importance for myelin synthesis. Mbp mRNA is transported from the nucleus to the plasma membrane and is translated locally at the axon–glial contact site. Axonal properties such as diameter or electrical activity influence the degree of myelination. As oligodendrocytes can myelinate many axonal segments with varying properties, localized MBP translation represents an important part of a rapid and axon-tailored synthesis machinery. MBP’s ability to compact cellular membranes may be problematic for the integrity of intracellular membranous organelles and can also explain why MBP is transported in oligodendrocytes in the form of an mRNA rather than as a protein. Here we review the recent findings regarding intracellular transport and signaling mechanisms leading to localized translation of Mbp mRNA in oligodendrocytes. More detailed insights into the MBP synthesis pathway are important for a better understanding of the myelination process and may foster the development of remyelination therapies for demyelinating diseases.
Background: Myelin basic protein (MBP) synthesis and Fyn kinase activity are important for CNS myelination. Results: Oligodendroglial hnRNP F is associated with RNA granules, a target of Fyn, and modulates MBP translation. Conclusion: hnRNP F is a crucial regulator of MBP synthesis. Significance: Dysregulation of hnRNP F levels as occurs in some white matter diseases will compromise myelination.
This review aims to summarize the current techniques to study myelination and remyelination in culture systems. We attempt to put these into historical context, and to identify the strengths and weaknesses of each approach, which vary depending on the experimental question to be tested. We discuss the difficulty and importance of quantification of myelination and in particular remyelination. Finally, we provide our predictions of how these techniques will and should develop in the future.
Re-canalization of cerebral vessels in ischemic stroke is pivotal to rescue dysfunctional brain areas that are exposed to moderate hypoxia within the penumbra from irreversible cell death. Goal of the present study was to evaluate the effect of moderate hypoxia followed by reoxygenation (MHR) on the evolution of reactive oxygen species (ROS) and blood-brain barrier (BBB) integrity in brain endothelial cells (BEC). BBB integrity was assessed in BEC in vitro and in microvessels of the guinea pig whole brain in situ preparation. Probes were exposed to MHR (2 hours 67-70 mmHg O2, 3 hours reoxygenation, BEC) or towards occlusion of the arteria cerebri media (MCAO) with or without subsequent reperfusion in the whole brain preparation. In vitro BBB integrity was evaluated using trans-endothelial electrical resistance (TEER) and transwell permeability assays. ROS in BEC were evaluated using 2′,7′-dichlorodihydrofluorescein diacetate (DCF), MitoSox and immunostaining for nitrotyrosine. Tight-junction protein (TJ) integrity in BEC, stainings for nitrotyrosine and FITC-albumin extravasation in the guinea pig brain preparation were assessed by confocal microscopy. Diphenyleneiodonium (DPI) was used to investigate NADPH oxidase dependent ROS evolution and its effect on BBB parameters in BEC. MHR impaired TJ proteins zonula occludens 1 (ZO-1) and claudin 5 (Cl5), decreased TEER, and significantly increased cytosolic ROS in BEC. These events were blocked by the NADPH oxidase inhibitor DPI. MCAO with or without subsequent reoxygenation resulted in extravasation of FITC-albumin and ROS generation in the penumbra region of the guinea pig brain preparation and confirmed BBB damage. BEC integrity may be impaired through ROS in MHR on the level of TJ and the BBB is also functionally impaired in moderate hypoxic conditions followed by reperfusion in a complex guinea pig brain preparation. These findings suggest that the BBB is susceptible towards MHR and that ROS play a key role in this process.
The adsorption of zinc chloride on calcite, dolomite and Casubstituted magnesite crystals from aqueous solution is treated theoretically; and a standard adsorption process is thereby rigorously defined. The thermodynamic characteristics Δ F0θ, Δ H0θ and Δ S0θ are determined for this process by means of adsorption isotherm data at various temperatures with crystals of measured surface area. It is found that about 10% of the adsorption sites probably available on calcite are occupied by zinc when the equilibrium Zn++aq concentration is 0.90 × 10‐6 M at 25.1° C. The Ca‐magnesite shows a somewhat greater affinity for zinc ion than calcite, while dolomite is intermediate. The temperature coefficients of Δ F0θ are opposite in sign for calcite and the other two minerals. The resulting endothermic heats of adsorption of Zn++aq on the dolomite and the Ca‐magnesite (Δ H0θ = 8.21 ± 2.4 and 22.7 ± 5.9 kcal/mole at about 27° C, respectively), as well as the corresponding very large positive entropies of adsorption (Δ S0θ = 56 ± 8 and 106 ± 20 cal/deg × mole at about 27° C, respectively) indicate that Zn++aq is dehydrated when adsorbed by these two minerals. The known compatability of Zn++ with the MgCO3 crystal lattice is suggested as the reason for the strong interaction of this ion with the dolomite and Ca‐magnesite, relative to calcite.
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