Journal Article


Marina Lynch
Derek Costello



female receptor activation genetics neurons deficiency rna double stranded magnesium male interferon inducers excitatory postsynaptic potentials physiology animals newborn brain function pharmacology in vitro techniques negative impact toll like receptor 3 mice inbred c57bl dose response relationship drug poly i c mice transgenic animals receptors interferon synaptic plasticity excitatory amino acid transporter 1 cells cultured mice nerve net interferon beta toll like receptors metabolism immunology inflammation infection gene expression regulation cytology hippocampus nr2b interictal long term potentiation drug effects neuroglia slc1a3 protein mouse

Toll-like receptor 3 activation modulates hippocampal network excitability, via glial production of interferon-β (2013)

Abstract The family of toll-like receptors (TLR) plays a major role in innate immunity due to their pathogen-recognition abilities. TLR3 is a sensor for double-stranded RNA, and regulates host-defense responses to several viruses, via the production of type I interferons. Interferon-? (IFN?) is a primary product of TLR3 activation, and its transcription is elevated in the CNS response to the synthetic TLR3 ligand, polyinosinic-polycytidylic acid (poly(I:C)). Peripheral infections, along with TLR-induced inflammatory mediators, are known to have detrimental effects on brain function, exerting a negative impact on cognitive impairment and enhancing seizure susceptibility. In the current study, we assessed hippocampal function in vitro, in response to systemic delivery of a TLR3 agonist. Unlike agonists of other TLRs, intraperitoneal injection of poly(I:C) did not adversely affect evoked short- and long-term synaptic plasticity in mouse hippocampal slices. However, sustained and interictal-like spontaneous activity was observed in CA1 pyramidal cells in response to poly(I:C) and this was associated with alterations in the expression of phosphorylated NR2B subunit-containing NMDA receptors and an astrocyte-specific glutamate/aspartate transporter (GLAST) which impact on extracellular glutamate concentration and contribute to the genesis of epileptiform activity. We provide evidence that the production of IFN? from microglia and astrocytes, and using mice deficient in the type I IFN receptor ? 1 (IFNAR1), demonstrate that its subsequent activation is likely to underlie the TLR3-mediated modulation of hippocampal excitability.
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Full list of authors on original publication

Marina Lynch, Derek Costello

Experts in our system

Marina Annetta Lynch
Trinity College Dublin
Total Publications: 80