The Cerebellum

, Volume 8, Issue 3, pp 163–174

Cuprizone Treatment Induces Distinct Demyelination, Astrocytosis, and Microglia Cell Invasion or Proliferation in the Mouse Cerebellum

  • Angela Groebe
  • Tim Clarner
  • Werner Baumgartner
  • Jon Dang
  • Cordian Beyer
  • Markus Kipp
Article

Abstract

Demyelination of the cerebellum is a well-known phenomenon in human multiple sclerosis (MS). Concordantly, patients with MS frequently developed symptoms deriving from cerebellar lesions, i.e., dysmetria leading to hand dexterity impairment. Important advances in MS research have been made as a direct or indirect consequence of the establishment of adequate animal models. In this study, we used the cuprizone mouse model to investigate cerebellar demyelination in young adult male mice. The myelin status was analyzed by immunohistochemistry for proteolipoprotein and electron microscopy. The expression and presence of oligodendrocyte, astroglial, and microglia markers were supplementary studied. Cuprizone intoxication induced an almost complete demyelination of cerebellar nuclei. Cerebellar cortex regions were not (cortical gray matter) or only marginally (cortical white matter) affected. In addition, the affected areas displayed hypertrophic and hyperplastic astrocytosis accompanied by microglia or macrophage invasion. We conclude that cuprizone-induced demyelination pictures cerebellar deep gray matter involvement but not cerebellar cortex pathology as described for human MS. Behavioral changes after cuprizone described for this animal model may not only result from effects on commissural fiber tracts but also can arise from cerebellar demyelination.

Keywords

Cuprizone Cerebellum Astrocytes Microglia Oligodendrocyte 

Abbreviations

APC

adenomatous polyposis coli protein

CCx

cerebellar cortex

CM

cerebellar marrow

CNS

central nervous system

cuprizone

bis-cyclohexanone oxaldihydrazone

EAE

experimental autoimmune encephalomyelitis

GFAP

glial fibrillary acidic protein

GL

granular layer

HPRT

hypoxanthine-guanine phosphoribosyltransferase

Iba-1

ionized calcium binding adaptor molecule

IHC

immunohistochemistry

IN

interpositus nucleus

LCN

lateral cerebellar nucleus

MBP

myelin basic protein

MCN

medial cerebellar nucleus

ML

molecular layer

MRI

magnet resonance imaging

MS

multiple sclerosis

PL

pyramidal layer

PLP

proteolipoprotein

rt

reverse transcription

RT

real time

WM

white matter

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Angela Groebe
    • 1
  • Tim Clarner
    • 1
  • Werner Baumgartner
    • 2
  • Jon Dang
    • 1
  • Cordian Beyer
    • 1
  • Markus Kipp
    • 1
  1. 1.Faculty of Medicine, Institute of NeuroanatomyRWTH Aachen UniversityAachenGermany
  2. 2.Department of Cellular Neurobionics, Institute of ZoologyRWTH Aachen UniversityAachenGermany

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