Journal of Molecular Neuroscience

, Volume 60, Issue 1, pp 46–62

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

  • Sigal Liraz-Zaltsman
  • Rami Yaka
  • Dalia Shabashov
  • Esther Shohami
  • Anat Biegon
Article

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.

Keywords

Cognitive deficits NMDA receptors Endotoxin LPS DCS Neuroinflammation 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Sigal Liraz-Zaltsman
    • 1
    • 2
  • Rami Yaka
    • 2
  • Dalia Shabashov
    • 2
  • Esther Shohami
    • 2
  • Anat Biegon
    • 1
    • 3
  1. 1.The Joseph Sagol Neuroscience CenterSheba Medical CenterRamat GanIsrael
  2. 2.Department of Pharmacology, School of PharmacyHebrew UniversityJerusalemIsrael
  3. 3.Department of NeurologyStony Brook University School of MedicineStony BrookUSA

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