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Max-Planck-Institut für Experimentelle Medizin
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Julia M Edgar, BSc(Hons), PhD, FHEA
Department of Neurogenetics
Max Planck Institute of Experimental Medicine
Hermann-Rein-Strasse 3
D-37075 Goettingen

Phone: +49551 3899-785
e-mail: Edgar@em.mpg.de


Research is focussed on understanding glial-axonal interaction in the central nervous system white matter, and in particular, how dysfunction of the central nervous system myelin producing cell, the oligodendrocyte, adversely affects axonal health. We have shown, using a variety of transgenic mouse models, that normal oligodendrocyte integrity and function is required for the long-term support of axonal integrity. Although the mechanisms are still not fully understood, our data indicate that the oligodendrocyte modulates fast axonal transport, possibly by supporting axonal energy requirements. Our findings have implications for understanding axonal degeneration in neurodegenerative disorders such as multiple sclerosis, the leukodystrophies and spastic paraplegia. We use transgenic mouse models, cell transplantation, axonal transport assays, time-lapse imaging methodologies and an in vitro model of myelination to examine the interactions between axons and white matter glia.




Mice overexpressing proteolipid protein (Plp1) gene products (Plp1-transgenic mice) synthesise myelin initially, but subsequently the myelin degenerates. Fast axonal transport is focally perturbed at sites of active demyelination where microglial numbers are elevated. In the optic nerve of Plp1-transgenic mice, demyelination progresses in a rostral to caudal direction, so that by postnatal day 120 the retinal portion of the nerve is completely demyelinated (A), while the optic tract remains partially myelinated (B). Axonal transport is focally perturbed in regions of active demyelination as demonstrated by the accumulation of retrogradely transported cholera toxin B subunit (CtB; green) in focal, neurofilament-containing (red) axonal swellings (C). When injected into the eye and rostral colliculus, respectively, both anterogradely (red) and retrogradely (green) transported CtB accumulate in some swellings, demonstrating that the associated axon is intact (D-F). Bar in C: 10 µm. Bar in F: 5 µm






An in vitro model of central nervous system myelination is used to examine the interaction between glia and axons. (A) Myelinating culture labelled with antibodies to myelin basic protein (red), neurofilament (blue) and Caspr (green). (B) When cultures are prepared from mice expressing a cytosolic fluorescent protein such as td-tomato (red), the oligodendrocyte soma and the non-compact myelin are labelled. In this case the culture was fixed and stained with an antibody to myelin basic protein (green).




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