Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia

Edgar, Julia M.; McLaughlin, Mark; Yool, D. A.; Zhang, Su Chun; Fowler, Jill H.; Montague, Paul; Barrie, Jennifer A.; McCulloch, M. C.; Duncan, Ian D.; Garbern, James; Nave, Klaus‐Armin; Griffiths, I. R.

doi:10.1083/jcb.200312012

Cited by 293 publications

(302 citation statements)

References 52 publications

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“…Aberrant transport and accumulation of organelles in the PNP region is a frequent accompaniment of myelin protein mutations (Salzer, 2003), being reported, for example, in mice with mutations of PLP or CNPase (Lappe-Siefke et al, 2003;Edgar et al, 2004). However, a striking finding in the Caspr mutant mice is that mitochondria accumulate in the nodal region out of proportion to other membranous organelles.…”

Section: Potential Mechanisms Of Nmv Formationmentioning

confidence: 84%

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier

2006

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Mitochondria and other membranous organelles are frequently enriched in the nodes and paranodes of peripheral myelinated axons, particularly those of large caliber. The physiologic role(s) of this organelle enrichment and the rheologic factors that regulate it are not well understood. Previous studies suggest that axonal transport of organelles across the nodal/paranodal region is locally regulated. In this study, we have examined the ultrastructure of myelinated axons in the sciatic nerves of mice deficient in the contactin-associated protein (Caspr), an integral junctional component. These mice, which lack the normal septate-like junctions that promote attachment of the glial (paranodal) loops to the axon, contain aberrant mitochondria in their nodal/ paranodal regions. These mitochondria are typically large and swollen and occupy prominent varicosities of the nodal axolemma. In contrast, mitochondria located outside the nodal/paranodal regions of the myelinated axons appear normal. These findings suggest that paranodal junctions regulate mitochondrial transport and function in the axoplasm of the nodal/paranodal region of myelinated axons of peripheral nerves. They further implicate the paranodal junctions in playing a role, either directly or indirectly, in the local regulation of energy metabolism in the nodal region.

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Section: Potential Mechanisms Of Nmv Formationmentioning

confidence: 84%

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier

2006

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“…32 It is also known that interactions between oligodendrocytes and neurons influence the activity and health of neurons. 33 Studies have suggested that neurons become vulnerable to cell death in the absence of oligodendrocytes. 34,35 However, the interrelationship between neuronal dysfunction and demyelination are not completely understood.…”

Section: Discussionmentioning

confidence: 99%

T-Cell-Mediated Disruption of the Neuronal Microtubule Network

Shriver

Dittel

2006

The American Journal of Pathology

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During the course of the central nervous system autoimmune disease multiple sclerosis (MS), damage to myelin leads to neurological deficits attributable to demyelination and conduction failure. However, accumulating evidence has indicated that axonal injury is also a predictor of MS clinical disease. Using the animal model of MS, experimental autoimmune encephalomyelitis (EAE), we examined whether axonal dysfunction occurred early in disease and correlated with disease symptoms. We tracked axons during EAE by using transgenic mice that express yellow fluorescent protein (YFP) in neurons. At the onset of disease, we observed a loss of YFP fluorescence in the spinal cord in areas that coincided with immune cell infiltration, before prominent demyelination. These inflammatory lesions also exhibited evidence of axonal injury but not axonal loss. During the recovery phase of EAE, the return of YFP fluorescence occurred in parallel with the resolution of inflammation. Using in vitro cultured neurons expressing YFP, we demonstrated that encephalitogenic T cells alone directed the destabilization of microtubules within neurites , resulting in a change in the pattern of YFP fluorescence. This study provides evidence that encephalitogenic T cells directly cause reversible axonal dysfunction at the onset of neurological deficits during an acute central nervous system inflammatory attack.

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“…The relative number of NG2 cells varies in different types of MS lesion in different reports [30][31][32][33][34][35][36] .…”

Section: Remyelination In Multiple Sclerosis (Ms): Ng2 Cells Functionmentioning

confidence: 99%

Roles of NG2 glial cells in diseases of the central nervous system

Zhao

2011

Neurosci. Bull.

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Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia

Cited by 293 publications

References 52 publications

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier

T-Cell-Mediated Disruption of the Neuronal Microtubule Network

Roles of NG2 glial cells in diseases of the central nervous system

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