Re-expression of N-cadherin in remyelinating lesions of experimental inflammatory demyelination.
The cell adhesion molecule N-cadherin is involved in several processes during central nervous system development, but also in certain pathologic conditions in the adult brain, including tumorigenesis and Alzheimer's disease. N-cadherin function in inflammatory demyelinating disease has so far not been investigated. In vitro studies suggest a role of N-cadherin in myelination; on the other hand N-cadherin has been implicated in the formation of the glial scar, which is believed to impede remyelination. The aim of our study was to investigate the expression pattern of N-cadherin immunoreactivity in experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein (MOG-EAE), an animal model closely mimicking multiple sclerosis. It allows a detailed evaluation of all stages of de- and remyelination during lesion development. Immunopathological evaluation was performed on paraffin-embedded CNS sections sampled at days 20 to 120 post immunization. We found a predominant expression of N-cadherin on oligodendrocytes in early remyelinating lesions, while in fully remyelinated shadow plaques there was no detectable immunoreactivity for N-cadherin. This expression pattern indicates a role of N-cadherin in the initiation of remyelination, most likely by providing a guidance between myelin lamellae and oligodendrocytes. Once the initial contact is made N-cadherin is then rapidly downregulated and virtually absent after completion of the repair process, analog to its known role in developmental myelination. Our results show that N-cadherin plays an important role in creating a remyelination-facilitating environment.
Department of Neurology, Medical University Graz, Austria. sonja.hochmeister@medunigraz.at
S
S
Hochmeister
M
M
Romauch
J
J
Bauer
T
T
Seifert-Held
R
R
Weissert
C
C
Linington
H P
HP
Hartung
F
F
Fazekas
M K
MK
Storch
D000818:Animals; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009185:Myelin Proteins / Q000096:biosynthesis / Q000235:genetics; D009186:Myelin Sheath / Q000502:physiology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D051381:Rats; D013997:Time Factors
D015820:Cadherins; C571328:Mog protein, rat; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein