Exaggerated NMDA mediated LTD in a mouse model of Down syndrome and pharmacological rescuing by memantine

Learn Mem. 2011 Nov 18;18(12):774-8. doi: 10.1101/lm.024182.111. Print 2011 Dec.

Abstract

The Ts65Dn mouse is the best-studied animal model for Down syndrome. In the experiments described here, NMDA-mediated or mGluR-mediated LTD was induced in the CA1 region of hippocampal slices from Ts65Dn and euploid control mice by bath application of 20 µM NMDA for 3 min and 50 µM DHPG for 5 min, respectively. We found that Ts65Dn mice display exaggerated NMDA-induced, but not mGluR-induced, LTD in the CA1 region of the hippocampus compared with euploid control animals. In addition, this abnormal level of LTD can be pharmacologically rescued by the NMDA receptor antagonist memantine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Down Syndrome* / drug therapy
  • Down Syndrome* / genetics
  • Down Syndrome* / pathology
  • Electric Stimulation
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • In Vitro Techniques
  • Long-Term Synaptic Depression / drug effects*
  • Long-Term Synaptic Depression / genetics
  • Memantine / therapeutic use*
  • Methoxyhydroxyphenylglycol / analogs & derivatives
  • Methoxyhydroxyphenylglycol / pharmacology
  • Mice
  • Mice, Mutant Strains
  • N-Methylaspartate / pharmacology*
  • Time Factors
  • Trisomy / pathology

Substances

  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Methoxyhydroxyphenylglycol
  • N-Methylaspartate
  • 3,4-dihydroxyphenylglycol
  • Memantine