Gene-environment interactions modulating cognitive function and molecular correlates of synaptic plasticity in Huntington's disease transgenic mice

Jess Nithianantharajah*, Christopher Barkus, Mark Murphy, Anthony J. Hannan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

151 Citations (Scopus)

Abstract

Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by motor, cognitive and psychiatric symptoms. Here, we show that R6/1 (HD) mice have deficits in short-term hippocampal-dependent memory prior to onset of motor symptoms. HD mice also exhibit impaired performance on a test of long-term spatial memory, however, environmental enrichment enhanced spatial learning and significantly ameliorated this memory deficit in HD mice. Analysis of the presynaptic vesicle protein synaptophysin showed no differences between standard-housed wild-type and HD littermates, however, enrichment increased synaptophysin levels in the frontal cortex and hippocampus in both groups. In comparison, analysis of postsynaptic proteins revealed that HD animals show decreased levels of PSD-95 and GluR1, but no change in levels of gephyrin. Furthermore, at 12 weeks of age when we observe a beneficial effect of enrichment on spatial learning in HD mice, enrichment also delays the onset of a deficit in hippocampal PSD-95 levels. Our results show that cognitive deficits in HD mice can be ameliorated by environmental enrichment and suggest that changes in synaptic composition may contribute to the cognitive alterations observed.

Original languageEnglish
Pages (from-to)490-504
Number of pages15
JournalNeurobiology of Disease
Volume29
Issue number3
DOIs
Publication statusPublished - Mar 2008
Externally publishedYes

Keywords

  • Environmental enrichment
  • GluR1
  • Hippocampus
  • Huntington's disease
  • Learning and memory
  • Polyglutamine
  • PSD-95
  • R6/1
  • Synaptic proteins
  • Synaptophysin

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