Cuprizone feed formulation influences the extent of demyelinating disease pathology

Abstract

Cuprizone is a copper-chelating agent that induces pathology similar to that within some multiple sclerosis (MS) lesions. The reliability and reproducibility of cuprizone for inducing demyelinating disease pathology depends on the animals ingesting consistent doses of cuprizone. Cuprizone-containing pelleted feed is a convenient way of delivering cuprizone, but the efficacy of these pellets at inducing demyelination has been questioned. This study compared the degree of demyelinating disease pathology between mice fed cuprizone delivered in pellets to mice fed a powdered cuprizone formulation at an early 3 week demyelinating timepoint. Within rostral corpus callosum, cuprizone pellets were more effective than cuprizone powder at increasing astrogliosis, microglial activation, DNA damage, and decreasing the density of mature oligodendrocytes. However, cuprizone powder demonstrated greater protein nitration relative to controls. Furthermore, mice fed control powder had significantly fewer mature oligodendrocytes than those fed control pellets. In caudal corpus callosum, cuprizone pellets performed better than cuprizone powder relative to controls at increasing astrogliosis, microglial activation, protein nitration, DNA damage, tissue swelling, and reducing the density of mature oligodendrocytes. Importantly, only cuprizone pellets induced detectable demyelination compared to controls. The two feeds had similar effects on oligodendrocyte precursor cell (OPC) dynamics. Taken together, these data suggest that demyelinating disease pathology is modelled more effectively with cuprizone pellets than powder at 3 weeks. Combined with the added convenience, cuprizone pellets are a suitable choice for inducing early demyelinating disease pathology.

Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice

“…By mixing the cuprizone with the powdered food source, the dose is dependent on the amount consumed by each mouse and reliant on consistent mixing of the formulation. There are now pellets containing cuprizone available, however, reports that the pellets produce both less consistent [ 62 , 87 ] and more consistent [ 88 ] demyelination than the powdered chow formulation vary study to study. Furthermore, there have been studies to administer the cuprizone via oral gavage to ensure a consistent dose was delivered [ 89 , 90 ], however, this requires more handling and stress on the animals, and may lead to oesophageal perforation with daily administration for up to 6 weeks.…”

Sulforaphane, an Nrf-2 Agonist, Modulates Oxidative Stress and Inflammation in a Rat Model of Cuprizone-Induced Cardiotoxicity and Hepatotoxicity

“…CPZ is a well-known neurotoxicant that is commonly used to induce demyelination and oligodendroglial death by stimulating mitochondrial dysfunction and provoking oxidative stress by increasing mitochondrial generation of reactive oxygen species (ROS) [1,43]. Herein, we investigated CPZ as a cardiotoxic and hepatotoxic chemical and examined the potential protective activities of SF against CPZ-induced The animal weight is an essential "variable" for reliable CPZ-provoked toxicity [44].…”

“…Cuprizone (oxalic acid bis (cyclohexylidene hydrazide) is a copper-chelating agent that is used experimentally to provoke demyelination pathology similar to that of multiple sclerosis (MS) [ 1 ]. Dietary administration of CPZ stimulates copper deficiency [ 2 ] and triggers dysfunction of the copper-dependent electron carrier “cytochrome oxidase” which is an essential component of oxidative phosphorylation [ 3 ].…”

Bu Shen Yi Sui Capsule Promotes Myelin Repair by Modulating the Transformation of A1/A2 Reactive Astrocytes In Vivo and In Vitro

“…It has been shown that glial cell-mediated neuroinflammation exacerbates oligodendrocyte injury and remyelination failure in the CPZ model [ 54 ]. Therefore, modification of the glial cell-mediated neuroinflammatory microenvironment can ameliorate myelin injury and promote repair processes.…”