Inhibition of neutral sphingomyelinase-2 perturbs brain sphingolipid balance and spatial memory in mice

Nino Tabatadze, Alena Savonenko, Hongjun Song, Veera Venkata Ratnam Bandaru, Michael Chu, Norman Haughey

Research output: Contribution to journalArticle

Abstract

The sphingolipid ceramide is a bioactive signaling lipid that is thought to play important roles in modulating synaptic activity, in part by regulating the function of excitatory postsynaptic receptors. However, the molecular mechanisms by which ceramide exerts its effects on synaptic activity remain largely unknown. We recently demonstrated that a rapid generation of ceramide by neutral sphingomyelinase-2 (nSMase2; also known as "sphingomyelin phosphodiesterase-3") played a key role in modulating excitatory postsynaptic currents by controlling the insertion and clustering of NMDA receptors (Wheeler et al. [2009] J. Neurochem. 109:1237-1249). We now demonstrate that nSMase2 plays a role in memory. Inhibition of nSMase2 impaired spatial and episodic-like memory in mice. At the molecular level, inhibition of nSMase2 decreased ceramide, increased PSD-95, increased the number of AMPA receptors, and altered the subunit composition of NMDA receptors. Our study identifies nSMase2 as an important component for efficient memory formation and underscores the importance of ceramide in regulating synaptic events related to learning and memory.

Original languageEnglish (US)
Pages (from-to)2940-2951
Number of pages12
JournalJournal of Neuroscience Research
Volume88
Issue number13
DOIs
StatePublished - Oct 2010

Fingerprint

Sphingomyelin Phosphodiesterase
Sphingolipids
Ceramides
Brain
N-Methyl-D-Aspartate Receptors
AMPA Receptors
Episodic Memory
Excitatory Postsynaptic Potentials
Cluster Analysis
Spatial Memory
Inhibition (Psychology)
Learning
Lipids

Keywords

  • AMPA
  • Ceramide
  • Memory
  • NMDA
  • Sphingomyelinase
  • Synapse

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Inhibition of neutral sphingomyelinase-2 perturbs brain sphingolipid balance and spatial memory in mice. / Tabatadze, Nino; Savonenko, Alena; Song, Hongjun; Bandaru, Veera Venkata Ratnam; Chu, Michael; Haughey, Norman.

In: Journal of Neuroscience Research, Vol. 88, No. 13, 10.2010, p. 2940-2951.

Research output: Contribution to journalArticle

Tabatadze, Nino ; Savonenko, Alena ; Song, Hongjun ; Bandaru, Veera Venkata Ratnam ; Chu, Michael ; Haughey, Norman. / Inhibition of neutral sphingomyelinase-2 perturbs brain sphingolipid balance and spatial memory in mice. In: Journal of Neuroscience Research. 2010 ; Vol. 88, No. 13. pp. 2940-2951.
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