Following the vesicular transport of MAG in rat-oligodendrocytes 

 By Inge Smolders

Multiple Sclerosis or simply MS is a demyelinating disease of the central nervous system (CNS). In the CNS, myelin is formed from processes that extend from the oligodendrocyte and then wrap in a spiral fashion around a particular segment of the axon (Larocca 2002). Myelin is essential for saltatory conduction of the electrical impulse along the axon and thus for the fast communication between nerve cells. If it is absent or deficient, communication is malfunctioning and neurological symptoms of MS, that involve various degrees of paralysis and altered or lost sensation, appear.

As mentioned before, the oligodendrocyte is responsible for the production of myelin. Myelin has a characteristic composition composed of 70 % lipids (enriched in glycosphingolipids) and 30 % proteins [myelin associated protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), myelin associated protein (MAG),…] (figure 1).

Fig 1: Myelinating glial cells, myelin structure and composition in the peripheral nervous system (PNS) and in the central nervous system (CNS). (Baumann 2001)

As shown in figure 2, each protein has its particular location and newly synthesized proteins arrive at their place by means of vesicular transport.

Fig 2. Subdomains of myelin and localization of myelin proteins. (Kim 1999)

This study focuses on MAG which is preferentially lost in type III of MS. Type III has a high prevalence in the acute phase of the disease and hypoxia is thought to play a pivotal role in this type (Lassmann 2003).

We plan to label MAG with EGFP (enhanced green fluorescent protein) and transfect adult oligodendrocytes, isolated from the brain of the rat. The confocal microscope will be used to monitor the route of newly synthesized MAG-EGFP-proteins towards the periaxonal plasma membrane (figure 3). 

Fig. 3 Myelin biogenesis related vesicle transport in oligodendrocytes (Larocca 2002)

My research concerns the question how hypoxia influences this vesicular transport of MAG. Several hypotheses can be put forward. Almost every step in the transport of this transmembrane protein could undergo the nefast influence of hypoxia.
It is also possible that hypoxia interferes with the synthesis of the integral protein. However, under hypoxic conditions/ type III MS, PLP and MOG are still present. The hypothesis then implies that hypoxia would selectively cause the disappearance of MAG.

REFERENCES:

1. Myelin biogenis: vesicle transport in oligodendrocytes. Neurochemical research Larocca J.N., Rodriguez-Gabin A.G., Vol. 27 No. 11, 2002 pg. 1313-1329

2. Biology of Oligodendrocyte and myelin in the mammalian central nervous system. Physiological reviews Baumann N., Pham-Dinh D., Vol. 81, No.2, 2001 pg. 871-891

3. Myelin glycosphingolipid/cholesterol-enriched microdomains selectively sequester the non-compact myelin proteins CNP and MOG. J Neurocytol. Kim T., Pfeiffer S.E., 28(4-5), 1999 pg. 281-93

4. Hypoxia-like tissue injury as a component of multiple sclerosis lesions. J Neurol Sci. Lassmann H., 15;206(2), 2003 pg. 187-91