alexa Elevated sulfatide levels in neurons cause lethal audiogenic seizures in mice.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Glycomics & Lipidomics

Author(s): van Zyl R, Gieselmann V, Eckhardt M

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Abstract Galactosylceramide (GalCer) and 3-O-sulfo-GalCer (sulfatide) are abundant sphingolipids in myelinating glial cells. However, low levels of GalCer and sulfatide have also been found in neurons, though their physiological role in these cells is unknown. Transgenic mice over-expressing UDP-galactose : ceramide galactosyltransferase (CGT) under control of the Thy1.2 promoter synthesize C18 : 0 fatty acid containing GalCer and sulfatide in neurons. Depending on the genetic background, these transgenic mice have a significantly reduced life span. Transgenic mice were extremely sensitive to sound stimuli and displayed lethal audiogenic seizures after relatively mild acoustic stimulation, i.e., key jangling. CGT-transgenic mice additionally over-expressing the adenosine 3'-phospho 5'-phosphosulfate : cerebroside sulfotransferase were more sensitive to audiogenic seizure induction than mice expressing only the CGT-transgene. This correlated with the higher sulfatide content in neuronal plasma membranes of the double-transgenic mice compared with CGT-transgenic mice, and strongly suggests that lethal audiogenic seizures are caused by elevated sulfatide levels in transgenic neurons. CGT-transgenic mice will be a useful model to further investigate how sulfatide affects functional properties of neurons. This article was published in J Neurochem and referenced in Journal of Glycomics & Lipidomics

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