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Significant glial alterations in response to iron loading in a novel organotypic hippocampal slice culture model.

ABSTRACT: Aberrant iron deposition in the brain is associated with neurodegenerative disorders including Multiple Sclerosis, Alzheimer's disease and Parkinson's disease. To study the collective response to iron loading, we have used hippocampal organotypic slices as a platform to develop a novel ex vivo model of iron accumulation. We demonstrated differential uptake and toxicity of iron after 12?h exposure to 10??M ferrous ammonium sulphate, ferric citrate or ferrocene. Having established the supremacy of ferrocene in this model, the cultures were then loaded with 0.1-100??M ferrocene for 12?h. One ?M ferrocene exposure produced the maximal 1.6-fold increase in iron compared with vehicle. This was accompanied by a 1.4-fold increase in ferritin transcripts and mild toxicity. Using dual-immunohistochemistry, we detected ferritin in oligodendrocytes, microglia, but rarely in astrocytes and never in neurons in iron-loaded slice cultures. Moreover, iron loading led to a 15% loss of olig2-positive cells and a 16% increase in number and greater activation of microglia compared with vehicle. However, there was no appreciable effect of iron loading on astrocytes. In what we believe is a significant advance on traditional mono- or dual-cultures, our novel ex vivo slice-culture model allows characterization of the collective response of brain cells to iron-loading.

SUBMITTER: Healy S

PROVIDER: S-EPMC5093415 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Significant glial alterations in response to iron loading in a novel organotypic hippocampal slice culture model.

Healy Sinead S McMahon Jill J Owens Peter P FitzGerald Una U

Scientific reports 20161103

Aberrant iron deposition in the brain is associated with neurodegenerative disorders including Multiple Sclerosis, Alzheimer's disease and Parkinson's disease. To study the collective response to iron loading, we have used hippocampal organotypic slices as a platform to develop a novel ex vivo model of iron accumulation. We demonstrated differential uptake and toxicity of iron after 12 h exposure to 10 μM ferrous ammonium sulphate, ferric citrate or ferrocene. Having established the supremacy of ...[more]

PMID: 27808258

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Dataset Information

Significant glial alterations in response to iron loading in a novel organotypic hippocampal slice culture model.

Publications

Significant glial alterations in response to iron loading in a novel organotypic hippocampal slice culture model.

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