Cuprizone treatment induces distinct demyelination, astrocytosis, and microglia cell invasion or proliferation in the mouse cerebellum.
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.
Groebe
Angela
A
Faculty of Medicine, Institute of Neuroanatomy, RWTH Aachen University, 52074 Aachen, Germany.
Clarner
Tim
T
Baumgartner
Werner
W
Dang
Jon
J
Beyer
Cordian
C
Kipp
Markus
M
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D003471:Cuprizone / Q000494:pharmacology*; D003711:Demyelinating Diseases / Q000139:chemically induced*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D008996:Monoamine Oxidase Inhibitors; D018991:Myelin Proteolipid Protein; C047516:Plp1 protein, mouse; D012333:RNA, Messenger; D003471:Cuprizone