Decreased expression of hypothalamic neuropeptides in Huntington disease transgenic mice with expanded polyglutamine-EGFP fluorescent aggregates

Svetlana Kotliarova, Nihar R. Jana, Naoaki Sakamoto, Masaru Kurosawa, Haruko Miyazaki, Munenori Nekooki, Hiroshi Doi, Yoko Machida, Kit Wong Hon, Taishi Suzuki, Chiharu Uchikawa, Yuri Kotliarov, Kazuyo Uchida, Yoshiro Nagao, Utako Nagaoka, Akira Tamaoka, Kiyomitsu Oyanagi, Fumitaka Oyama, Nobuyuki Nukina

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

Huntington disease is caused by polyglutamine (polyQ) expansion in huntingtin. Selective and progressive neuronal loss is observed in the striatum and cerebral cortex in Huntington disease. We have addressed whether expanded polyQ aggregates appear in regions of the brain apart from the striatum and cortex and whether there is a correlation between expanded polyQ aggregate formation and dysregulated transcription. We generated transgenic mouse lines expressing mutant truncated N-terminal huntingtin (expanded polyQ) fused with enhanced green fluorescent protein (EGFP) and carried out a high-density oligonucleotide array analysis using mRNA extracted from the cerebrum, followed by TaqMan RT-PCR and in situ hybridization. The transgenic mice formed expanded polyQ-EGFP fluorescent aggregates and this system allowed us to directly visualize expanded polyQ aggregates in various regions of the brain without performing immunohistochemical studies. We show here that polyQ-EGFP aggregates were intense in the hypothalamus, where the expression of six hypothalamic neuropeptide mRNAs, such as oxytocin, vasopressin and cocaine-amphetamine- regulated transcript, was down-regulated in the transgenic mouse brain without observing a significant loss of hypothalamic neurons. These results indicate that the hypothalamus is susceptible to aggregate formation in these mice and this may result in the down-regulation of specific genes in this region of the brain.

Original languageEnglish
Pages (from-to)641-653
Number of pages13
JournalJournal of Neurochemistry
Volume93
Issue number3
DOIs
Publication statusPublished - May 2005
Externally publishedYes

Keywords

  • GeneChip
  • Huntingtin
  • Huntington disease
  • Hypothalamus
  • Polyglutamine
  • Striatum

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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