Journal of Molecular Neuroscience

, Volume 43, Issue 3, pp 268–274 | Cite as

Glial Amyloid Precursor Protein Expression is Restricted to Astrocytes in an Experimental Toxic Model of Multiple Sclerosis

  • Tim Clarner
  • Jan Philipp Buschmann
  • Cordian Beyer
  • Markus Kipp


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.


Amyloid precursor protein Astroglia Microglia Cuprizone Demyelination 



Alzheimers disease


Amyloid precursor protein


Corpus callosum


Complementary DNA




Experimental Autoimmune Encephalitis


Glial fibrillary acidic protein


Hydrogen peroxide


Hypoxanthine guanine phosphoribosyltransferase


Ionized calcium-binding adaptor molecule 1


Moloney Murine Leukemia Virus


Multiple sclerosis


Optical density


Protein loading buffer Tris (2-carboxyethyl)phosphine Hydrochloride


Proteolipid protein

Real-time RT-PCR

Real-time reverse transcriptase quantitative polymerase chain reaction


Sodium dodecylsulfate polyacrylamide gel electrophoresis


Standard error of the mean

TAQ Polymerase

Thermus aquaticus DNA polymerase


Tris buffered saline

Th1 cells

T helper 1 cells


Tumor necrosis factor alpha



This project was supported by the START-Program (M.K.) of the Faculty of Medicine, RWTH Aachen University and by the Hertie-Foundation (M.K.). We would like to thank H. Helten for excellent technical support.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Tim Clarner
    • 1
  • Jan Philipp Buschmann
    • 1
  • Cordian Beyer
    • 1
  • Markus Kipp
    • 1
  1. 1.Institute of Neuroanatomy, Faculty of MedicineRWTH Aachen UniversityAachenGermany

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