Exploring potential strategies to enhance memory and cognition in aging mice [version 1; peer review: 1 approved with reservations]

Background: Aging population is rapidly expanding worldwide, and age-related cognitive impairments prove detrimental for achieving a better productive and quality of life. Lack of effective therapies for age-related cognitive impairment focuses attention on developing preventive strategies, such as nutritional interventions, cell therapies and environmental manipulations. The objective of the present study was to explore the comparative benefits of potential memory-enhancing strategies like supplementation of choline (Ch) and docosahexaenoic acid (DHA) or administration of human embryonic kidney stem cell conditioned media (HEK-CM) or exposure to environmental enrichment (EE), that attenuates cognitive impairments in aging mice. Methods: 12-month-old CF1 male mice were subdivided [n=6/group] into normal aging control (NAC), saline vehicle control (SVC), Ch-DHA, EE, heat-inactivated HEK-CM (HIHEK-CM) and HEK-CM mice. Spatial working and reference memory were assessed using an eight-arm radial maze test and cognition using a novel object recognition test (NORT). Results: Spatial memory and cognition were decreased in normal aging mice. Aged mice exposed to dietary Ch-DHA or HEK-CM showed significant enhancement in spatial learning tasks, memory and cognition compared to the same in age-matched NAC mice. Ch-DHA and HEK-CM treated mice committed significantly lesser reference memory errors and attained a higher percentage of correct choices in spatial learning and memory tasks. Moreover, on testing for cognition in NORT, significantly higher number of visits to the novel object was observed in Ch-DHA supplemented and HEK-CM administered aging mice whereas HEK-CM and EE mice groups showed significantly greater number of visits to familiar object, when compared to same in age-matched NAC and HIHEK-CM groups, respectively. Conclusion: Supplementation of Ch-DHA and HEK-CM treatment strategies have a higher potential [~ 20-30%] for enhancing spatial learning, memory and cognition in normal aged mice, whereas exposure to EE seems to enhance only their short-term memory.