title: Polyunsaturated fatty acid biostatus, phospholipase A2activity and brain white matter microstructure across adolescence.
abstract: Adolescence is a period of major brain white matter (WM) changes, and membrane lipid metabolism likely plays a critical role in brain WM myelination. Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential components of cell membranes including oligodendrocytes, and LC-PUFA release and turnover in membranes is regulated by phospholipase A2enzymes. To investigate the role of membrane lipid metabolism in healthy WM myelination across adolescence, the present study examined the relationship between membrane LC-PUFA biostatus, phospholipase A2activity, and brain WM microstructure in healthy subjects aged 9-20years (n=30). Diffusion tensor imaging (DTI) was performed to measure average fractional anisotropy (FA) and diffusivity (indices sensitive to WM myelination) of nine major cerebral WM tracts. Blood samples were collected to measure erythrocyte membrane fatty acid concentrations and plasma intracellular phospholipase A2activity (inPLA2). Plasma inPLA2activity showed a significant U-curved association with WM radial diffusivity, and an inverted U-curved association with WM FA, independent of age. A significant positive linear correlation was observed between docosahexaenoic acid concentration and axial diffusivity in the corpus callosum. These findings suggest that there may be optimal physiological inPLA2activity levels associated with healthy WM myelination in late childhood and adolescence. Myelination may be mediated by cleavage of docosahexaenoic acid from membrane phospholipids by inPLA2. These findings have implications for our understanding of the role of LC-PUFA homeostasis in myelin-related neurodevelopmental disorders.
authors.affiliation: Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45219, USA. Electronic address: mcnamar@ucmail.uc.edu.
authors.forename: Robert K
authors.initials: RK
authors.lastname: McNamara
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY 11004, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. Electronic address: philip.szeszko@mssm.edu.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Szeszko
authors.affiliation: Department of Psychiatry, University Hospital Jena, D-07743 Jena, Germany. Electronic address: stefan.smesny@med.uni-jena.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Smesny
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY 11004, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. Electronic address: tikuta@umail.iu.edu.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ikuta
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY 11004, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. Electronic address: pderosse@NSHS.edu.
authors.forename: Pamela
authors.initials: P
authors.lastname: DeRosse
authors.affiliation: Laboratory Genetic Metabolic Diseases, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands. Electronic address: f.m.vaz@amc.uva.nl.
authors.forename: Frédéric M
authors.initials: FM
authors.lastname: Vaz
authors.affiliation: Department of Dermatology, University Hospital Jena, Erfurter Straße 35, D-07743 Jena, Germany. Electronic address: berko.milleit@med.uni-jena.de.
authors.forename: Berko
authors.initials: B
authors.lastname: Milleit
authors.affiliation: Department of Dermatology, University Hospital Jena, Erfurter Straße 35, D-07743 Jena, Germany. Electronic address: christina.hipler@med.uni-jena.de.
authors.forename: Uta-Christina
authors.initials: UC
authors.lastname: Hipler
authors.affiliation: Department of Dermatology, University Hospital Jena, Erfurter Straße 35, D-07743 Jena, Germany. Electronic address: C.Wiegand@med.uni-jena.de.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Wiegand
authors.affiliation: Department of Dermatology, University Hospital Jena, Erfurter Straße 35, D-07743 Jena, Germany. Electronic address: jana.hesse@med.uni-jena.de.
authors.forename: Jana
authors.initials: J
authors.lastname: Hesse
authors.affiliation: Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Australia; Centre for Youth Mental Health, The University of Melbourne, Parkville VIC 3052, Australia. Electronic address: amminger@unimelb.edu.au.
authors.forename: G Paul
authors.initials: GP
authors.lastname: Amminger
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY 11004, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. Electronic address: amalhotra@nshs.edu.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Malhotra
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY 11004, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. Electronic address: petersbart@hotmail.com.
authors.forename: Bart D
authors.initials: BD
authors.lastname: Peters
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging / Q000254:growth & development* / Q000378:metabolism*; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism; D054467:Phospholipases A2 / Q000097:blood*; D012737:Sex Factors; D066127:White Matter / Q000000981:diagnostic imaging / Q000254:growth & development* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D054467:Phospholipases A2
keywords: adolescence; development; myelin; phospholipase; polyunsaturated fatty acids; white matter