Spatial learning deficit in aged heterozygous Cav2.1 channel mutant mice, rolling mouse Nagoya.
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.
Takahashi
Eiki
E
Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. etakahashi@brain.riken.jp
Niimi
Kimie
K
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*
D020864:Calcium Channels, N-Type