Environmental enrichment reduces neuronal intranuclear inclusion load but has no effect on messenger RNA expression in a mouse model of Huntington disease

Caroline L Benn, Ruth Luthi-Carter, Alexandre Kuhn, Ghazaleh Sadri-Vakili, Kwabena L Blankson, Sudeb C Dalai, Darlene R Goldstein, Tara Spires-Jones, Joel Pritchard, James M Olson, Anton van Dellen, Anthony J Hannan, Jang-Ho J Cha

Research output: Contribution to journalArticlepeer-review

Abstract

Huntington disease (HD) is a fatal neurodegenerative disease with no effective treatment. In the R6/1 mouse model of HD, environmental enrichment delays the neurologic phenotype onset and prevents cerebral volume loss by unknown molecular mechanisms. We examined the effects of environmental enrichment on well-characterized neuropathological parameters in a mouse model of HD. We found a trend toward preservation of downregulated neurotransmitter receptors in striatum of environmentally enriched mice and assessed possible enrichment-related modifications in gene expression using microarrays. We observed similar gene expression changes in R6/1 and R6/2 transgenic mice but found no specific changes in enrichment-related microarray expression profiles in either transgenic or wild-type mice. Furthermore, specific corrections in transprotein-induced transcriptional dysregulation in R6/1 mice were not detected by microarray profiling. However, gene-specific analyses suggested that long-term environmental enrichment may beneficially modulate gene expression dysregulation. Finally, environmental enrichment significantly decreased neuronal intranuclear inclusion load, despite unaffected transgene expression levels. Thus, the therapeutic effects of environmental enrichment likely contribute to decreasing aggregated polyglutamine protein levels without exerting strong effects on gene expression.
Original languageEnglish
Pages (from-to)817-27
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume69
Issue number8
DOIs
Publication statusPublished - Aug 2010

Keywords

  • Age Factors
  • Animals
  • Corpus Striatum
  • Disease Models, Animal
  • Environment
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Huntington Disease
  • Intranuclear Inclusion Bodies
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Nerve Tissue Proteins
  • Neurons
  • Nuclear Proteins
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger
  • Radioligand Assay
  • Receptors, Neurotransmitter
  • Trinucleotide Repeat Expansion

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