Hippocampal calbindin-1 immunoreactivity correlate of recognition memory performance in aged mice.

Aging-related dysregulation of neuronal calcium metabolism, which not only involves the control of calcium fluxes but also the cytosolic calcium buffering system such as calbindin-1 (Calb1), may disturb synaptic plasticity and thereby memory functioning. Calb1 expression has been shown to affect hippocampal long-term potentiation and learning and to play a neuroprotective role in animal models of ischemic brain injury and neurodegenerative disorders. We hypothesize that memory performance in aged mice correlates with neuronal Calb1 protein expression in the hippocampal formation. We studied a set of 18 aged and 22 young male C57BL/6N mice, in which the aged group performed poorer than the young in single-trial novel object recognition testing (two-tailed p=0.005, U test). Apparent decreases in the Calb1 immunoreactivity (measured by quantitative immunohistochemistry) in aged mice compared to that in young mice were not statistically significant either in the hippocampal CA1 subfield or dentate gyrus. In the aged mouse group, levels of Calb1 immunoreactivity both in the CA1 subfield and dentate gyrus correlated directly with the measure of recognition memory performance (Spearman rank correlation r(s)=0.47 and 0.48, two-tailed p=0.047 and 0.044, respectively). Our results suggest that hippocampal Calb1 expression affects memory performance in aged mice probably via its role in maintaining neuronal calcium homeostasis. Alternatively, our finding of lower Calb1 immunoreactivity with poorer memory performance in aged mice might be attributed to saturation of Calb1 protein by higher levels of intracellular calcium, due to aging-related dysregulation of neuronal calcium fluxes.