Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson's disease

Authors

  • Sarah K. Abbott PhD,

    Corresponding author
    1. Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia
    2. School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia
    • Correspondence to: Dr. Brett Garner, Illawarra Health and Medical Research Institute, University of Wollongong, NSW 2522, Australia; brettg@uow.edu.au

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  • Hongyun Li PhD,

    1. Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia
    2. School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia
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  • Sonia Sanz Muñoz MSc,

    1. Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia
    2. School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia
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  • Bianca Knoch PhD,

    1. Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia
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  • Marijka Batterham PhD,

    1. National Institute of Applied Statistics Research Australia, University of Wollongong, Wollongong, New South Wales, Australia
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  • Karen E. Murphy BSc (Hons),

    1. Neuroscience Research Australia, Sydney, New South Wales, Australia
    2. School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
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  • Glenda M. Halliday PhD,

    1. Neuroscience Research Australia, Sydney, New South Wales, Australia
    2. School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
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  • Brett Garner PhD

    1. Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia
    2. School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia
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  • Funding agencies: National Health & Medical Research Council of Australia (1008307 to G.M.H. and B.G.; 630434 to G.M.H.; 630752 to K.E.M.; 630445 to B.G.); Australian Research Council (FT0991986 to B.G.).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

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. © 2013 International Parkinson and Movement Disorder Society

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