Cuprizone effect on myelination, astrogliosis and microglia attraction in the mouse basal ganglia.
Multiple sclerosis is the leading cause of neurological disability in young adults affecting more than two million people worldwide. Although multiple sclerosis is generally considered as white matter disease, distinct pathological alterations are also found in the grey matter. Involvement of basal ganglia seems to be related to a set of symptoms such as fatigue, impaired cognition, and movement disturbance. Since no appropriate animal model for studying cortical deep grey matter demyelination is established, we reassessed the cuprizone mouse model to investigate basal ganglia demyelination. Mice were fed cuprizone for different time intervals. The myelin status was analyzed by classical histological staining and immunohistochemistry for myelin proteins and glia markers. Expression of oligodendrocyte and astroglia were investigated by PCR. Cuprizone intoxication induced a severe demyelination of distinct cortical deep grey matter sub-regions. Striosmomes, located within the caudate-putamen and the ventral part of the caudate nucleus displayed intense demyelination, whereas those within the globus pallidus and the head of the caudate nucleus were not affected. The matrix region, however, was equally affected in the medial and lateral region. Besides demyelination, we observed hypertrophic and hyperplastic astrocytosis and microglia cell invasion/local proliferation in the demyelinated areas. Young adult and aged mice were similarly affected as well as mice with different genetic backgrounds. We conclude that cuprizone-induced demyelination provides an adequate animal model to investigate appropriate therapy strategies for the prevention of cortical deep grey matter demyelination. The heterogeneity in local demyelination points at beginning remyelination during ongoing demyelination.
Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, D-52074 Aachen, Germany.
Friederike
F
Pott
Stefan
S
Gingele
Tim
T
Clarner
Jon
J
Dang
Werner
W
Baumgartner
Cordian
C
Beyer
Markus
M
Kipp
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D005911:Gliosis / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009185:Myelin Proteins; D003471:Cuprizone