Synapse Loss Induced by Interleukin1β Requires Pr

Authors: Anjuli Mishra Hee Jung Kim Angela H Shin Stanley A Thayer

Publish Date: 2012/02/05

Volume: 7, Issue: 3, Pages: 571-578

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Abstract

Interleukin1β IL1β is an inflammatory cytokine that exerts marked effects on neuronal function and survival Here we examined the effects of IL1β on synapses between rat hippocampal neurons in culture using an imagingbased assay to quantify clusters of the scaffolding protein postsynaptic density 95 fused to green fluorescent protein Treatment with IL1β for 24 h induced a 23 ± 3 loss in the number of synaptic sites Pharmacological studies indicated that synapse loss was mediated by the IL1 receptor with subsequent activation of two pathways COX2mediated prostaglandin production and postsynaptic activation of a Src family tyrosine kinase were required Presynaptic release of glutamate with subsequent activation of NMDA receptors was necessary for IL1βinduced synapse loss Neither Src activation nor prostaglandin E2 PGE2 application alone was sufficient to reduce the number of synapses However in cells expressing constitutively active or pharmacologically activated Src PGE2 induced synapse loss Thus IL1β reduces the number of synaptic connections by simultaneously activating multiple pathways that require both pre and postsynaptic activity These results highlight targets that may prove important for pharmacotherapy of neuroinflammatory disease

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