Evidence for a Developmental Role for TLR4 in Learning and Memory

Eitan Okun, Boaz Barak, Ravit Saada-Madar, Sarah M. Rothman, Kathleen J. Griffioen, Nicholas Roberts, Kamilah Castro, Mohamed R. Mughal, Mario A. Pita, Alexis Michelle Stranahan, Thiruma V. Arumugam, Mark P. Mattson

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Toll-like receptors (TLRs) play essential roles in innate immunity and increasing evidence indicates that these receptors are expressed in neurons, astrocytes and microglia in the brain where they mediate responses to infection, stress and injury. Very little is known about the roles of TLRs in cognition. To test the hypothesis that TLR4 has a role in hippocampus-dependent spatial learning and memory, we used mice deficient for TLR4 and mice receiving chronic TLR4 antagonist infusion to the lateral ventricles in the brain. We found that developmental TLR4 deficiency enhances spatial reference memory acquisition and memory retention, impairs contextual fear-learning and enhances motor functions, traits that were correlated with CREB up-regulation in the hippocampus. TLR4 antagonist infusion into the cerebral ventricles of adult mice did not affect cognitive behavior, but instead affected anxiety responses. Our findings indicate a developmental role for TLR4 in shaping spatial reference memory, and fear learning and memory. Moreover, we show that central TLR4 inhibition using a TLR4 antagonist has no discernible physiological role in regulating spatial and contextual hippocampus-dependent cognitive behavior.

Original languageEnglish (US)
Article numbere47522
JournalPloS one
Volume7
Issue number10
DOIs
StatePublished - Oct 11 2012

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Hippocampus
learning
Toll-Like Receptors
Learning
Data storage equipment
hippocampus
Fear
antagonists
Cerebral Ventricles
fearfulness
Lateral Ventricles
Brain
Microglia
mice
Innate Immunity
Astrocytes
Cognition
cerebral ventricles
Up-Regulation
brain

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Okun, E., Barak, B., Saada-Madar, R., Rothman, S. M., Griffioen, K. J., Roberts, N., ... Mattson, M. P. (2012). Evidence for a Developmental Role for TLR4 in Learning and Memory. PloS one, 7(10), [e47522]. https://doi.org/10.1371/journal.pone.0047522

Evidence for a Developmental Role for TLR4 in Learning and Memory. / Okun, Eitan; Barak, Boaz; Saada-Madar, Ravit; Rothman, Sarah M.; Griffioen, Kathleen J.; Roberts, Nicholas; Castro, Kamilah; Mughal, Mohamed R.; Pita, Mario A.; Stranahan, Alexis Michelle; Arumugam, Thiruma V.; Mattson, Mark P.

In: PloS one, Vol. 7, No. 10, e47522, 11.10.2012.

Research output: Contribution to journalArticle

Okun, E, Barak, B, Saada-Madar, R, Rothman, SM, Griffioen, KJ, Roberts, N, Castro, K, Mughal, MR, Pita, MA, Stranahan, AM, Arumugam, TV & Mattson, MP 2012, 'Evidence for a Developmental Role for TLR4 in Learning and Memory', PloS one, vol. 7, no. 10, e47522. https://doi.org/10.1371/journal.pone.0047522
Okun E, Barak B, Saada-Madar R, Rothman SM, Griffioen KJ, Roberts N et al. Evidence for a Developmental Role for TLR4 in Learning and Memory. PloS one. 2012 Oct 11;7(10). e47522. https://doi.org/10.1371/journal.pone.0047522
Okun, Eitan ; Barak, Boaz ; Saada-Madar, Ravit ; Rothman, Sarah M. ; Griffioen, Kathleen J. ; Roberts, Nicholas ; Castro, Kamilah ; Mughal, Mohamed R. ; Pita, Mario A. ; Stranahan, Alexis Michelle ; Arumugam, Thiruma V. ; Mattson, Mark P. / Evidence for a Developmental Role for TLR4 in Learning and Memory. In: PloS one. 2012 ; Vol. 7, No. 10.
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