Is Sphingosine 1-Phosphate (S1P) Produced by Sphingosine Kinase 2 (SphK2); Important for Learning and Memory?

Abstract

Sphingosine 1-Phosphate (S1P) is a potent lipid-derived signaling molecule that signals through its own family of five G-protein coupled receptors, promoting neurotransmission and neuroprotection. Recent research has demonstrated a loss of S1P in individuals with pre-clinical and clinical Alzheimer ’s disease (AD), particularly in brain regions that are heavily affected by the disease. The loss of S1P was attributed to loss of its biosynthetic enzyme, sphingosine kinase 2 (SphK2). Given that loss of S1P in the hippocampus and temporal cortex tracks closely with neuronal atrophy in AD brains, we hypothesized that loss of SphK2 in mice may produce deficits in spatial, recognition, and associative learning and memory. These aspects of memory were tested using the elevated plus maze, cheeseboard paradigm and fear conditioning tests in SphK2-/- and Wild-type (WT) mice. The findings of this study are not indicative of deficits in learning and memory but indicate an anxiety phenotype in the SphK2-/- mice as indicated by the behavioral tests. The total S1P content was markedly lowered in the brains of SphK2-/- mice as compared to the WT mice.