We have determined that the sphingosine kinase/S1P receptor axis has a significant role during neurodegeneration. We used a well-established Sandhoff mouse model of neurodegeneration, which included neuronal apoptosis, inflammation and gliosis. In order to determine if S1P production was important during the neurodegenerative process we deleted the Sphk1 gene in the Sandhoff model. We found a significant improvement in life span and clinical condition of these mice compared with the control Sandhoff mice with a normal Sphk1 gene. These results indicate that Sphk1 expression may have contributed to the neurodegenerative course. Future experiments will address the mechanism of the improved course of the disease.
|Camprubi-Robles, Maria; Mair, Norbert; Andratsch, Manfred et al. (2013) Sphingosine-1-phosphate-induced nociceptor excitation and ongoing pain behavior in mice and humans is largely mediated by S1P3 receptor. J Neurosci 33:2582-92|
|Saadat, Laleh; Dupree, Jeffrey L; Kilkus, John et al. (2010) Absence of oligodendroglial glucosylceramide synthesis does not result in CNS myelin abnormalities or alter the dysmyelinating phenotype of CGT-deficient mice. Glia 58:391-8|