314 S1P Signaling in Neuronal Apoptosis; Links to Resistance and Vulnerability to Ischemic-Induced Neuronal Cell Death. Issue Volume 65:Issue CN(2018)Supplement 1 (16th August 2018)

• Record Type: Journal Article
• Authors: Rashad, Sherif; Niizuma, Kuniyasu; Sato-Maeda, Mika; Saigusa, Daisuke; Tominaga, Teiji
• Is Part Of: Neurosurgery. Volume 65:Issue CN(2018)Supplement 1
• Page Start: 127
• Page End: 127
• Publication Date: 2018-08-16
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1093/neuros/nyy303.314
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract: INTRODUCTION: Sphingosine-1-phosphate (S1P) is a sphingolipid molecule produced by the action of sphingosine kinases (SphK) on sphingosine. It possesses various intracellular functions through its interactions with intracellular proteins or via its action on 5 G-protein-coupled cell membrane receptors. Following transient global cerebral ischemia (tGCI), only the CA1 subregion of the hippocampus undergoes apoptosis. METHODS: In vivo experiments: tGCI model was produced in adult male rats by bilateral carotid occlusion coupled with hypotension. S1P levels were evaluated by LC-MS. qPCR was used to evaluate enzymes in the S1P cascade. FTY720 was injected to rats at a dose of 1 mg/kg after ischemia and rats were evaluated by histology and behavioral testing. RESULTS: We found that S1P was upregulated earlier in CA3 than in CA1. This was associated with upregulation of SphK1 in both regions; however, SphK2 was downregulated quickly in CA3. S1P lyase was also downregulated in CA3, but not in CA1. Spinster 2, the S1P exporter, was upregulated early in both regions, but was quickly downregulated in CA3. Together, these effects explain the variable levels of S1P in the CA1 and CA3 areas and demonstrate that S1P levels play a role in the preferential resistance of the CA3 subregion to tGCI-induced ischemia. FTY720 did not improve neuronal survival in the CA1 subregion, indicating that these effects were due to intracellular S1P accumulation. CONCLUSION: These findings suggest that intracellular S1P levels affect neuronal cell fate following tGCI.