Age-related spatial cognitive impairment is correlated with increase of synaptotagmin 1 in dorsal hippocampus in SAMP8 mice.

The age-related decline of learning and memory is a common phenomenon in humans and animals, even though the underlying mechanism is not yet known. In the present study, we propose that synaptotagmin 1 (Syt 1) might be a synaptic protein involved in the loss of learning and memory with aging. To test this hypothesis, the age-related spatial cognitive ability of 36 P8 mice (15 mice aged 4 months, 11 mice aged 8 months and 10 mice aged 13 months) was measured in a Morris water maze. After the behavioral test, both the protein and mRNA levels of Syt 1 were determined in the dorsal hippocampus by means of immunocytochemistry and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. In the Morris water maze, the latency of the 4-month mice to find the submerged platform was significantly shorter than that of the older mice, while there were no significant differences between the 8- and 13-month-old mice in this respect. Compared to the 4-month-old mice, the Syt 1 protein in the 13-month-old mice was significantly increased in almost all layers of each subfield of the hippocampus. The average level of Syt 1 mRNA in the dorsal hippocampus of the P8 mice had not changed with aging. The latency of the 13-month-old P8 mice tested in the Morris water maze was positively correlated with the Syt 1 immunoreactivity in four circuit-specific regions in the dorsal hippocampus. Interestingly, the latency in the Morris water maze was also positively correlated with the level of Syt 1 mRNA in the dorsal hippocampus in individual aged P8 mouse. These results suggest that increased Syt 1 in the dorsal hippocampus in aged mice might be responsible for the age-related impairment of learning and memory.