DOI: 10.1101/502559Dec 20, 2018Paper

Microglia-dependent presynaptic disruption in an organotypic hippocampal slice culture model of neuroinflammation

BioRxiv : the Preprint Server for Biology
Olivia SheppardClaire S Durrant

Abstract

Background: Systemic inflammation, such as occurs during sepsis, bone fracture, infections or post-operative trauma, has been linked to synapse loss and cognitive decline in human patients and animal models. Organotypic hippocampal slice cultures (OHSCs) represent an underused tool in neuroinflammation; retaining much of the neuronal architecture, synaptic connections and diversity of cell types present in the hippocampus in vivo whilst providing convenient access to manipulate and sample the culture medium and observe cellular reactions as in other in vitro methods. Here we report the development of an OHSC model of synaptic disruption after aseptic inflammation and investigate the underlying mechanism. Methods: OHSCs were generated from P6-P9 C57BL/6, the APP transgenic TgCRND8 model, or wild-type littermate mice according to the interface method. Aseptic inflammation was induced via addition of lipopolysaccharide (LPS) and cultures were analysed for changes in synaptic proteins via western blot. qPCR and ELISA analysis of the slice tissue and culture medium respectively determined changes in gene expression and protein secretion. Microglia were selectively depleted using the toxin clodronate and the effect of IL1β was assess...Continue Reading

Related Concepts

Amyloid
Monoclonal Antibodies
Western Blotting
Fracture
Gene Expression
Hippocampus (Brain)
Inflammation
Lipopolysaccharides
Neuronal Plasticity
Neurons

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