Cortical Demyelination Is Prominent in the Murine Cuprizone Model and Is Strain-Dependent

Cuprizone-dependent demyelination is massive within the corpus callosum but also occurs within additional brain regions such as the cortex and hippocampus.

“cuprizone-dependent demyelination is massive within the corpus callosum but also occurs within additional brain regions such as the cortex and hippocampus (Koutsoudaki et al. 2009; Skripuletz et al. 2008; Steelman et al. 2012).”

Cortical demyelination can be observed after 3 weeks of cuprizone exposure and is almost complete after 6 weeks of cuprizone treatment.

“Cortical demyelination can be observed after 3 weeks of cuprizone exposure being almost complete after 6 weeks of cuprizone treatment (Skripuletz et al., 2008; Gudi et al., 2009).”

Demyelination peaks between 4.5 and 5 weeks of cuprizone exposure in the corpus callosum and between 5 and 6 weeks in the cortex and hippocampus.

“Demyelination peaks between 4.5 and 5 weeks of cuprizone exposure in the CC and between 5 and 6 weeks in the cortex and hippocampus (Hiremath et al., 1998; Matsushima and Morell, 2001; Skripuletz et al., 2008; Gudi et al., 2009; Koutsoudaki et al., 2009).”

A significantly stronger microgliosis is observed in the cerebellar white matter as compared to gray matter structures, probably primarily due to the higher amount of myelin content/debris.

“Probably primarily due to the higher amount of myelin content/debris, a significantly stronger microgliosis can be observed in the cerebellar white matter as compared to the gray matter structures (Skripuletz et al., 2008; Gudi et al., 2009).”

Strong astrogliosis comprising hypertrophy and hyperplasia of astrocytes occurs as a response to cuprizone treatment in different white and gray matter structures including the corpus callosum, hippocampus, cerebellum, cortex, and basal ganglia.

“Strong astrogliosis comprising hypertrophy and hyperplasia of astrocytes occurs as a response to cuprizone treatment in different white and gray matter structures for instance the CC (Matsushima and Morell, 2001; Gudi et al., 2009), hippocampus, (Koutsoudaki et al., 2009; Norkute et al., 2009), cerebellum, cortex (Skripuletz et al., 2008), and basal ganglia (Pott et al., 2009).”

Demyelination is pronounced in the corpus callosum and somato-sensory cortex region.

“While demyelination is pronounced in the corpus callosum and somato-sensory cortex region [109]”

Other mouse strains are also used sometimes in the cuprizone model.

“However, other strains are also used sometimes [7–10].”

In their study the authors challenged BALB/cJ mice with 0.2% cuprizone treatment of 6 weeks, and observed that cortical demyelination of BALB/cJ mice was incomplete, as opposed to C57BL/6 strain which shows no detectable cortical myelin at this stage.

“In their study the authors challenged BALB/cJ mice with 0.2% cuprizone treatment of 6 weeks, and observed that cortical demyelination of BALB/cJ mice was incomplete, as opposed to C57BL/6 strain which shows no detectable cortical myelin at this stage.”

Demyelination in the cortex induced by cuprizone treatment has also been shown by Skripuletz et al. to be affected by genetic background factors.

“In addition to the corpus callosum, demyelination in the cortex induced by cuprizone treatment has also been shown by Skripuletz et al. to be affected by genetic background factors [9].”

Strain differences have been reported for cortical demyelination induced by cuprizone.

“Recently, strain differences have been reported for cortical demyelination induced by cuprizone.”

BALB/cJ mice treated with 0.2% cuprizone have a similar pattern of demyelination in the corpus callosum but less demyelination and more microglia activation in the cortex compared with C57BL/6 mice.

“The BALB/cJ mice were reported to have a similar pattern of demyelination in the corpus callosum, but less demyelination and more microglia activation in the cortex as compared with C57BL/6 mice.”