Neuroinflammation-Induced Memory Deficits Are Amenable to Treatment with d-Cycloserine

Sigal Liraz-Zaltsman*, Rami Yaka, Dalia Shabashov, Esther Shohami, Anat Biegon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Cognitive deficits, especially memory loss, are common following many types of brain insults which are associated with neuroinflammation, although the underlying mechanisms are not entirely clear. The present study aimed to characterize the long-term cognitive and behavioral impairments in a mouse model of neuroinflammation in the absence of other insults and to evaluate the therapeutic potential of d-cycloserine (DCS). DCS is a co-agonist of the NMDA receptor that ameliorates cognitive deficits in models of TBI and stroke. Using a mouse model of global neuroinflammation induced by intracisternal (i.c.) administration of endotoxin (LPS), we found long-lasting microgliosis, memory deficits, impaired LTP, and reduced levels of the obligatory NR1 subunit of the NMDA receptor. A single administration of DCS, 1 day after i.c. LPS reduced microgliosis, reversed the cognitive deficits and restored LTP and NR1 levels. These results demonstrate that neuroinflammation alone, in the absence of trauma or ischemia, can cause persistent (>6 months) memory deficits linked to deranged NNMDA receptor function and suggest a possible role for NMDA co-agonists in reducing the cognitive sequelae of neuroinflammation.

Original languageAmerican English
Pages (from-to)46-62
Number of pages17
JournalJournal of Molecular Neuroscience
Volume60
Issue number1
DOIs
StatePublished - 1 Sep 2016

Bibliographical note

Publisher Copyright:
© 2016, Springer Science+Business Media New York.

Keywords

  • Cognitive deficits
  • DCS
  • Endotoxin
  • LPS
  • NMDA receptors
  • Neuroinflammation

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