Glial amyloid precursor protein expression is restricted to astrocytes in an experimental toxic model of multiple sclerosis.
The amyloid precursor protein is rapidly induced in reactive glia in response to pathological stimuli and inflammation. In this study, we investigated its expression in an experimental multiple sclerosis animal model, the cuprizone mouse model which reveals massive myelin loss. Cuprizone intoxication for 5 weeks induced immense demyelination of the corpus callosum and resulted in hypertrophic and hyperplastic astrocytosis accompanied by microglia/macrophage invasion. Using double-immunofluorescence, real-time quantitative PCR and Western Blot, we observed that activated astrocytes are the main source of amyloid precursor protein during demyelination. In order to rule out astrocytes, in general, responding to inflammatory and toxic compounds by amyloid precursor protein expression, neonatal astroglia cultures were exposed to various stimuli. Under control conditions, astroglial amyloid precursor protein was only moderately expressed. None of the treatments had a significant effect on its expression in vitro. Our results suggest that amyloid precursor protein is specifically up-regulated under cuprizone-induced demyelination. It remains to be further elucidated whether amyloid precursor protein-positive astrocytes are directly implicated in the pathological mechanism of demyelination.
Clarner
Tim
T
Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany.
Buschmann
Jan Philipp
JP
Beyer
Cordian
C
Kipp
Markus
M
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology; D003471:Cuprizone / Q000633:toxicity*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D009103:Multiple Sclerosis / Q000139:chemically induced* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D008996:Monoamine Oxidase Inhibitors; D012333:RNA, Messenger; D003471:Cuprizone