Toll-like receptor 3 activation modulates hippocampal network excitability, via glial production of interferon-β
Citation:
Derek A. Costello, and Marina A. Lynch., Toll-like receptor 3 activation modulates hippocampal network excitability, via glial production of interferon-β, Hippocampus, 23, 8, 2013, 696-707Abstract:
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.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
07/IN.1/B949
Author's Homepage:
http://people.tcd.ie/lynchmaDescription:
PUBLISHED
Author: COSTELLO, DEREK; LYNCH, MARINA
Type of material:
Journal ArticleCollections
Series/Report no:
Hippocampus23
8
Availability:
Full text availableSubject (TCD):
Immunology, Inflammation & InfectionDOI:
http://dx.doi.org/10.1002/hipo.2212Metadata
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