Impairment of neuropsychological behaviors in ganglioside GM3-knockout mice

Kimie Niimi, Chieko Nishioka, Tomomi Miyamoto, Eiki Takahashi, Ichiro Miyoshi, Chitoshi Itakura, Tadashi Yamashita

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The ganglioside GM3 synthase (SAT-I), encoded by a single-copy gene, is a primary glycosyltransferase for the synthesis of complex gangliosides. Although its expression is tightly controlled during early embryo development and postnatal development and maturation in the brain, the physiological role of ganglioside GM3 in the regulation of neuronal functions has not been elucidated. In the present study, we examined motor activity, cognitive and emotional behaviors, and drug administration in juvenile GM3-knockout (GM3-KO) mice. GM3-KO male and female mice showed hyperactivity in the motor activity test, Y-maze test, and elevated plus maze test. In the Y-maze test, there was significantly less spontaneous alternation behavior in GM3-KO male mice than in wild-type mice. In the elevated plus maze test, the amount of time spent on the open arms by GM3-KO male mice was significantly higher than that of sex-matched wild-type mice. In contrast, there was no significant difference between GM3-KO and wild-type female mice in these tests. Thus, juvenile GM3-KO mice show gender-specific phenotypes resembling attention-deficit hyperactivity disorder (ADHD), namely hyperactivity, reduced attention, and increased impulsive behaviors. However, administration of methylphenidate hydrochloride (MPH) did not ameliorate hyperactivity in either male or female GM3-KO mice. Although these data demonstrate the involvement of ganglioside GM3 in ADHD and the ineffectiveness of MPH, the first-choice psychostimulant for ADHD medication, our studies indicate that juvenile GM3-KO mice are a useful tool for neuropsychological studies.

Original languageEnglish
Pages (from-to)524-528
Number of pages5
JournalBiochemical and biophysical research communications
Volume406
Issue number4
DOIs
Publication statusPublished - 2011 Mar 25
Externally publishedYes

Keywords

  • Attention-deficit hyperactivity disorder (ADHD)
  • Elevated plus maze test
  • Ganglioside GM3
  • Knockout mouse
  • Methylphenidate hydrochloride (MPH)
  • Motor activity test

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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