Cuprizone-Induced Multiple Sclerosis
Cuprizone is a copper chelator, that causes rapid demyelination and gliosis, and rapid proliferation of glia subtypes. The cuprizone mouse model captures several aspects of Multiple Sclerosis (MS) pathology like demyelination / remyelination, cognitive decline, altered activity and motor deficits.
The cuprizone model is the most frequently used model among the toxin-induced MS models and is used to study mechanisms of oligodendrocyte turnover, gliosis as well as motor capabilities. This animal model is thus suitable to assess certain aspects of the MS pathology and to test pharmaceutical compounds.
C57Bl/6 mice were fed with 0.3 % cuprizone chow for 1 month. Behavioral changes were analyzed within the last week of cuprizone treatment.
Figure 1: Beam walk test, MAO activity and astrocytosis of C57BL/6 mice after 4 weeks of cuprizone treatment. A: latency to traverse a 10 mm wide square beam in seconds. B: MAO activity in brain lysates. C: Quantification of astrocytosis in the hippocampus by GFAP labeling. Mean + SEM; n = 10 per group; unpaired t-test/Mann Whitney test; ***p<0.001.
EAE Mouse Model of Multiple Sclerosis
Experimental autoimmune encephalomyelitis (EAE) shows many pathological similarities to Multiple Sclerosis (MS) and is therefore often used as model to mimic MS by injecting Myelin-Oligodendrocyte-Glycoprotein (MOG) in combination with pertussis toxin (PTX).
The EAE model is widely used as inducible MS model presenting commonly observed MS pathologies like demyelination, neuroinflammation as well as motor strength and coordination.
C57Bl/6 mice were injected with a MOG and PTX regime and clinical signs, motor coordination and spinal cord neuropathology was evaluated.
Figure 1: Clinical signs, motor deficits neurofilament-light chain levels and demyelination of EAE mice. EAE induced C57Bl/6 mice were tested for clinical signs (A), muscle strength in the wire suspension test (B), plasma neurofilament-light chain levels (C) compared to vehicle treated and EAE + Fingo treated mice and Luxol Fast Blue staining for myelin in EAE and Sham induced mice (D). A-C: n = 13 16 per group; Mean + SEM; Kruskal-Wallis One-way ANOVA followed by Dunn‘s multiple comparisons post hoc test; *p<0.05; **p<0.01; ***p<0.001. *EAE-Vehicle vs. Sham-Vehicle; #EAE-Fingo vs. EAE Vehicle. Fingo = Fingolimod.