Cuprizone feed formulation influences the extent of demyelinating disease pathology
| Autor: | C. Bartlett, Melinda Fitzgerald, Sarah C Hellewell, Alexander J Wright, Brittney R. Lins, Terence McGonigle, Chidozie C. Anyaegbu, Melissa Papini, Lillian M. Toomey, Andrew Warnock |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Pathology medicine.medical_specialty Multiple Sclerosis Myelin biology and repair Science Oligodendrocyte progenitor Article Corpus Callosum Cuprizone Mice medicine Demyelinating disease Animals Gliosis Chelating Agents Inflammation Multidisciplinary Chemistry Multiple sclerosis Body Weight Reproducibility of Results medicine.disease Animal Feed Astrogliosis Mice Inbred C57BL Disease Models Animal Oligodendroglia Astrocytes Medicine Microglia DNA Damage Demyelinating Diseases |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-16 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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