Sodium channel β4 subunit: Down-regulation and possible involvement in neuritic degeneration in Huntington's disease transgenic mice

Fumitaka Oyama, Haruko Miyazaki, Naoaki Sakamoto, Celine Becquet, Yoko Machida, Kumi Kaneko, Chiharu Uchikawa, Taishi Suzuki, Masaru Kurosawa, Tetsurou Ikeda, Akira Tamaoka, Takashi Sakurai, Nobuyuki Nukina

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

Abstract

Sodium channel β4 is a very recently identified auxiliary subunit of the voltage-gated sodium channels. To find the primarily affected gene in Huntington's disease (HD) pathogenesis, we profiled HD transgenic mice using a high-density oligonucleotide array and identified p4 as an expressed sequence tag (EST) that was significantly down-regulated in the striatum of HD model mice and patients. Reduction in β4 started at a presymptomatic stage in HD mice, whereas other voltage-gated ion channel subunits were decreased later. In contrast, spinal cord neurons, which generate only negligible levels of expanded polyglutamine aggregates, maintained normal levels of β4 expression even at the symptomatic stage. Overexpression of β4 induced neurite outgrowth in Neuro2a cells, and caused a thickening of dendrites and increased density of dendritic spines in hippocampal primary neurons, indicating that β4 modulates neurite outgrowth activities. These results suggest that down-regulation of β4 may lead to abnormalities of sodium channel and neurite degeneration in the striatum of HD transgenic mice and patients with HD.

Original languageEnglish
Pages (from-to)518-529
Number of pages12
JournalJournal of Neurochemistry
Volume98
Issue number2
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

Keywords

  • Huntington's disease
  • Neurite outgrowth activity
  • Polyglutamine
  • Sodium channel β4 subunit

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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