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Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-? plaque formation in organotypic hippocampal slice cultures.

ABSTRACT: The role of microglia in amyloid-? (A?) deposition is controversial. In the present study, an organotypic hippocampal slice culture (OHSC) system with an in vivo-like microglial-neuronal environment was used to investigate the potential contribution of microglia to A? plaque formation. We found that microglia ingested A?, thereby preventing plaque formation in OHSCs. Conversely, A? deposits formed rapidly in microglia-free wild-type slices. The capacity to prevent A? plaque formation was absent in forebrain microglia from young adult but not juvenile 5xFamilial Alzheimer's disease (FAD) mice. Since no loss of A? clearance capacity was observed in both wild-type and cerebellar microglia from 5xFAD animals, the high A?1-42 burden in the forebrain of 5xFAD animals likely underlies the exhaustion of microglial A? clearance capacity. These data may therefore explain why A? plaque formation has never been described in wild-type mice, and point to a beneficial role of microglia in AD pathology. We also describe a new method to study A? plaque formation in a cell culture setting.

SUBMITTER: Hellwig S

PROVIDER: S-EPMC4586757 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-β plaque formation in organotypic hippocampal slice cultures.

Hellwig Sabine S Masuch Annette A Nestel Sigrun S Katzmarski Natalie N Meyer-Luehmann Melanie M Biber Knut K

Scientific reports 20150929

The role of microglia in amyloid-β (Aβ) deposition is controversial. In the present study, an organotypic hippocampal slice culture (OHSC) system with an in vivo-like microglial-neuronal environment was used to investigate the potential contribution of microglia to Aβ plaque formation. We found that microglia ingested Aβ, thereby preventing plaque formation in OHSCs. Conversely, Aβ deposits formed rapidly in microglia-free wild-type slices. The capacity to prevent Aβ plaque formation was absent ...[more]

PMID: 26416689

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Dataset Information

Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-? plaque formation in organotypic hippocampal slice cultures.

Publications

Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-β plaque formation in organotypic hippocampal slice cultures.

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