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.
