title: Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson’s disease.
abstract: Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson’s disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case-control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase genes that regulate ceramide acyl chain composition in the same tissue using quantitative PCR. In PD anterior cingulate cortex but not occipital cortex, total ceramide and sphingomyelin levels were reduced from control levels by 53% (P < 0.001) and 42% (P < 0.001), respectively. Of the 13 ceramide and 15 sphingomyelin molecular lipid species identified and quantified, there was a significant shift in the ceramide acyl chain composition toward shorter acyl chain length in the PD anterior cingulate cortex. This PD-associated change in ceramide acyl chain composition was accompanied by an upregulation of ceramide synthase-1 gene expression, which we consider may represent a response to reduced ceramide levels. These data suggest a significant shift in ceramide function in lipid membranes and signaling pathways occurs in regions with PD pathology. Identifying the regulatory mechanisms precipitating this change may provide novel targets for future therapeutics.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Abbott
authors.forename: Hongyun
authors.initials: H
authors.lastname: Li
authors.forename: Sonia Sanz
authors.initials: SS
authors.lastname: Muñoz
authors.forename: Bianca
authors.initials: B
authors.lastname: Knoch
authors.forename: Marijka
authors.initials: M
authors.lastname: Batterham
authors.forename: Karen E
authors.initials: KE
authors.lastname: Murphy
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.forename: Brett
authors.initials: B
authors.lastname: Garner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002518:Ceramides / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D002518:Ceramides; D010088:Oxidoreductases; C108138:dihydroceramide desaturase