title: Spatial learning deficit in aged heterozygous Cav2.1 channel mutant mice, rolling mouse Nagoya.
abstract: Rolling Nagoya mice carrying Ca(v)2.1alpha1 gene mutation show ataxia, whereas heterozygous mice show no apparently abnormal behavior. It has been reported that Ca(v)2.1 regulates neurotransmitter release and that Ca(2+) influx through Ca(v)2.1 decreases with aging. Age-related decline in cognitive function could be at least partly attributable to decreases in Ca(v)2.1-related neurotransmission. In this study to examine age-related cognitive alterations in heterozygous mice, we used Y-maze and delayed spatial win-shift eight-arm radial-maze tests, and 2- and 22-month-old mice. Although there was no difference between 2-month-old heterozygous and wild-type mice, 22-month-old heterozygous mice showed decreased memory formation versus 2-month-old heterozygous mice in both tests. Expression analysis in forebrain showed that total Ca(v)2.1alpha1 mRNA, including wild-type and mutant-type Ca(v)2.1alpha1 mRNA, in 2-month-old heterozygous mice was expressed at a level similar to that in 22-month-old heterozygous mice. However, wild-type Ca(v)2.1alpha1 mRNA was expressed at a lower level in 22-month-old mice than in 2-month-old mice, and mutant-type Ca(v)2.1alpha1 mRNA was expressed at a higher level in 22-month-old versus 2-month-old mice. Our results suggest that aged heterozygous mice show deficits in spatial learning due to Ca(v)2.1 channel dysfunction and that heterozygous mice may be a useful model for examining mechanisms underlying age-related cognitive dysfunction.
authors.affiliation: Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. etakahashi@brain.riken.jp
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
authors.forename: Kimie
authors.initials: K
authors.lastname: Niimi
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001259:Ataxia / Q000235:genetics; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism*; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology*; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013037:Spatial Behavior / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*
chemical_list: D020864:Calcium Channels, N-Type