Correlation of increased hippocampal Sumo3 with spatial learning ability in old C57BL/6 mice

► It is unknown whether Sumo3 involves age-related cognitive decline. ► The old C57BL/6 mice showed markedly impaired ability of learning and memory. ► There is an increased level of Sumo3 in DH and VH in the old mice. ► The learning index of the old mice negatively correlated with Sumo3 in DH. ► Increased Sumo3 in DH might correlate with learning ability in old C57BL/6 mice. Age-related impairment of learning and memory is a common phenomenon in humans and animals, yet the underlying mechanism remains unclear. We hypothesize that a small ubiquitin-related modifier (Sumo) might correlate with age-related loss of learning and memory. To test this hypothesis, the present study evaluated age-related spatial learning and memory in C57BL/6 mice (25 aged 7 months and 21 aged 25 months) using a radial six-arm water maze (RAWM). After the behavioral test, the protein expression of Sumo3 was determined in different brain regions using Western blotting. The results showed that the 25-month-old mice had longer latency and a higher number of errors in both learning and memory phases in the RAWM task than the 7-month-old mice. Compared to the latter, the former's level of Sumo3 protein was significantly increased in the dorsal and ventral hippocampus. For the 25-month-old mice, the number of errors and the latency in the learning phase negatively correlated with the Sumo3 level in the dorsal hippocampus. These results suggest that increased Sumo3 in the hippocampus may be correlated with spatial learning ability in old C57BL/6 mice.