Testing the calcium hypothesis of aging in the rat hippocampus in vivo using manganese-enhanced MRI

In this study, we noninvasively tested the hypothesis that Mn2+-enhanced magnetic resonance imaging (MEMRI) is sensitive to age-related changes in Ca2+ influx occurring in the hippocampal region CA1. Uptake of Mn2+, an MRI contrast agent and Ca2+ surrogate with low cellular efflux rates (days to weeks), was measured in longitudinal MEMRI studies involving 2 separate groups of male Long-Evans rats: one group was studied at 2.5 and 7 months of age, whereas the other was studied at 7 and 19 months of age. Separate or combined analysis revealed that the extent of Mn2+ accumulation in CA1 significantly increased with age (p < 0.05). These results provide first-time in vivo confirmation of the calcium hypothesis of aging and justify future longitudinal studies combining MEMRI with behavioral testing to investigate mechanisms of age-related cognitive decline.