| First Author | Takahashi E | Year | 2009 |
| Journal | Exp Gerontol | Volume | 44 |
| Issue | 4 | Pages | 274-9 |
| PubMed ID | 19073246 | Mgi Jnum | J:146573 |
| Mgi Id | MGI:3837923 | Doi | 10.1016/j.exger.2008.11.006 |
| Citation | Takahashi E, et al. (2009) Spatial learning deficit in aged heterozygous Cav2.1 channel mutant mice, rolling mouse Nagoya. Exp Gerontol 44(4):274-9 |
| abstractText | 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. |
