Early Life Exposure to C₁₆-Ceramide Improves Learning and Short-Term Memory Behavior during Adulthood in Mice

Ceramides, structural components of the cell, are known to play a range of roles in glucose metabolism and apoptosis. C₁₆-ceramide, an abundant molecular species of endogenous ceramide, has not had its influence on learning and memory explored. We administered C₁₆-ceramide to mice immediately after weaning and examined the learning and memory behavior of these mice during adulthood. Mice given C₁₆-ceramide early in life showed improved adult learning/short-term memory behavior without affecting their glucose metabolism. Looking for a plausible mechanism for this, we found that calcium influx, CaMKII/CREB, and the Erk-relevant signaling transduction are increased after C₁₆-ceramide stimulation in primary neurons in vitro. Possible downstream epigenetic molecular events, such as H3K4 methylation and Egr-1 abundance, were also found to be upregulated. Utilizing J20 mice, an Alzheimer disease mice model in which mice were injected after weaning with C₁₆-ceramide, we found that these mice also show improved learning and short-term memory behavior when assessed by the Morris water maze test. Taken together, giving C₁₆-ceramide early in life would seem to benefit learning and short-term memory behavior during adulthood.