Cell death of oligodendrocytes or demyelination induced by overexpression of proteolipid protein depending on expressed gene dosage

Inoue, Yoshiro; Kagawa, Tetsushi; Matsumura, Yuko; Ikenaka, Kazuhiro; Mikoshiba, Katsuhiko

doi:10.1016/0168-0102(96)01039-5

Cited by 48 publications

(21 citation statements)

References 29 publications

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“…The optic nerves were removed, and postfixed with a 1% osmic acid solution and embedded in an epoxy resin (Inoue et al, 1996). Ultra-thin transverse sections were double-stained with a 2% uranyl acetate aqueous and mixed lead solution.…”

Section: Electron Microscopical Examinationsmentioning

confidence: 99%

Completion of myelin compaction, but not the attachment of oligodendroglial processes triggers K+ channel clustering

et al. 1999

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The characteristic localization of ion channels is crucial for the propagation of saltatory conduction in myelinated nerves. Voltage-gated Na(+) channels are located at nodes of Ranvier while voltage-gated K(+) channels are mainly found at juxtaparanodal regions. Recently, a humoral factor secreted by oligodendrocytes has been reported to induce clustering of Na(+) channels in CNS axons. However, the molecular mechanisms for K(+) channel clustering as well as the role of oligodendrocytes are still uncertain. To clarify whether myelin sheath itself can induce the distinct distribution of K(+) channels, we have investigated the localization of K(+) channels in adult and developing mouse optic nerves. The CNS axons from chronic demyelinating and hypomyelinating mice were also examined to determine if myelin sheaths were required for the maintenance of clusters. In all cases, the K(+) channel clustering correlated well with compact myelin, but not with the presence of oligodendrocytes, suggesting that, in contrast to Na(+) channel clustering, the formation of compact myelin is required for initiation as well as maintenance of K(+) channel clustering. In addition, postsynaptic density protein-95 (PSD-95) or its highly related protein was found colocalized with K(+) channels, suggesting that it may interact with K(+) channels to form clusters at juxtaparanodal regions.

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Section: Electron Microscopical Examinationsmentioning

confidence: 99%

Completion of myelin compaction, but not the attachment of oligodendroglial processes triggers K+ channel clustering

et al. 1999

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“…For example, Shiverer mice have a mutation in the gene that encodes myelin basic protein that results in a severe CNS hypomyelinating phenotype (Rosenbluth, 1980;Rosenbluth, 1981). Transgenic mice that overexpress the proteolipid protein (Plp) develop adult onset chronic demyelination (Kagawa et al, 1994;Inoue et al, 1996). In both model animals there is a dramatic upregulation of axonal Nav1.2 (Westenbroek et al, 1992;Boiko et al, 2001;Rasband et al, 2003a).…”

Section: Role Of Myelination In Nav Channel Subtype Switchingmentioning

confidence: 99%

Early events in node of Ranvier formation during myelination and remyelination in the PNS

et al. 2006

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Action potential conduction velocity increases dramatically during early development as axons become myelinated. Integral to this process is the clustering of voltage-gated Na + (Nav) channels at regularly spaced gaps in the myelin sheath called nodes of Ranvier. We show here that some aspects of peripheral node of Ranvier formation are distinct from node formation in the CNS. For example, at CNS nodes, Nav1.2 channels are detected first, but are then replaced by Nav1.6. Similarly, during remyelination in the CNS, Nav1.2 channels are detected at newly forming nodes. By contrast, the earliest Nav-channel clusters detected during developmental myelination in the PNS have Nav1.6. Further, during PNS remyelination, Nav1.6 is detected at new nodes. Finally, we show that accumulation of the cell adhesion molecule neurofascin always precedes Nav channel clustering in the PNS. In most cases axonal neurofascin (NF-186) accumulates first, but occasionally paranodal neurofascin is detected first. We suggest there is heterogeneity in the events leading to Nav channel clustering, indicating that multiple mechanisms might contribute to node of Ranvier formation in the PNS.

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“…tg/Ϫ mice show abnormal behavior Previous reports described that 2-month-old plp1 tg/Ϫ mice had neither symptoms nor histological signs of demyelination (Inoue et al, 1996;Ishibashi et al, 2003). However, CVs were significantly decreased in 2-month-old plp1 tg/Ϫ mice (Tanaka et al, 2006).…”

Section: Two-month-old Plp1mentioning

confidence: 99%

“…Previous studies demonstrated that at 2 months of age, the myelin in these mice was intact (Inoue et al, 1996), and Na ϩ and K ϩ channel clusters were formed normally at the node of Ranvier and its adjacent region, respectively (Ishibashi et al, 2003;Rasband et al, 2003). Although, at a much later stage, these mice undergo demyelination (Kagawa et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Mice with Altered Myelin Proteolipid Protein Gene Expression Display Cognitive Deficits Accompanied by Abnormal Neuron-Glia Interactions and Decreased Conduction Velocities

Tanaka

et al. 2009

Journal of Neuroscience

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Conduction velocity (CV) of myelinated axons has been shown to be regulated by oligodendrocytes even after myelination has been completed. However, how myelinating oligodendrocytes regulate CV, and what the significance of this regulation is for normal brain function remain unknown. To address these questions, we analyzed a transgenic mouse line harboring extra copies of the myelin proteolipid protein 1 ( plp1) gene ( plp1 tg/Ϫ mice) at 2 months of age. At this stage, the plp1 tg/Ϫ mice have an unaffected myelin structure with a normally appearing ion channel distribution, but the CV in all axonal tracts tested in the CNS is greatly reduced. We also found decreased axonal diameters and slightly abnormal paranodal structures, both of which can be a cause for the reduced CV. Interestingly the plp1 tg/Ϫ mice showed altered anxiety-like behaviors, reduced prepulse inhibitions, spatial learning deficits and working memory deficit, all of which are schizophrenia-related behaviors. Our results implicate that abnormalities in the neuron-glia interactions at the paranodal junctions can result in reduced CV in the CNS, which then induces behavioral abnormalities related to schizophrenia.

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Cell death of oligodendrocytes or demyelination induced by overexpression of proteolipid protein depending on expressed gene dosage

Cited by 48 publications

References 29 publications

Completion of myelin compaction, but not the attachment of oligodendroglial processes triggers K+ channel clustering

Completion of myelin compaction, but not the attachment of oligodendroglial processes triggers K+ channel clustering

Early events in node of Ranvier formation during myelination and remyelination in the PNS

Mice with Altered Myelin Proteolipid Protein Gene Expression Display Cognitive Deficits Accompanied by Abnormal Neuron-Glia Interactions and Decreased Conduction Velocities

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