title: Region-specific vulnerability to lipid peroxidation and evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the healthy adult human central nervous system.
abstract: Lipids played a determinant role in the evolution of the brain. It is postulated that the morphological and functional diversity among neural cells of the human central nervous system (CNS) is projected and achieved through the expression of particular lipid profiles. The present study was designed to evaluate the differential vulnerability to oxidative stress mediated by lipids through a cross-regional comparative approach. To this end, we compared 12 different regions of CNS of healthy adult subjects, and the fatty acid profile and vulnerability to lipid peroxidation, were determined by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS), respectively. In addition, different components involved in PUFA biosynthesis, as well as adaptive defense mechanisms against lipid peroxidation, were also measured by western blot and immunohistochemistry, respectively. We found that: i) four fatty acids (18.1n-9, 22:6n-3, 20:1n-9, and 18:0) are significant discriminators among CNS regions; ii) these differential fatty acid profiles generate a differential selective neural vulnerability (expressed by the peroxidizability index); iii) the cross-regional differences for the fatty acid profiles follow a caudal-cranial gradient which is directly related to changes in the biosynthesis pathways which can be ascribed to neuronal cells; and iv) the higher the peroxidizability index for a given human brain region, the lower concentration of the protein damage markers, likely supported by the presence of adaptive antioxidant mechanisms. In conclusion, our results suggest that there is a region-specific vulnerability to lipid peroxidation and offer evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the human central nervous system.
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Naudí
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Cabré
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, Department of Pathology and Experimental Therapeutics, University of Barcelona, E-08908, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Mayelin
authors.initials: M
authors.lastname: Dominguez-Gonzalez
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ayala
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Jové
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Mota-Martorell
authors.affiliation: Neurology Division, Hospital Santa Maria of Lleida, E-25006 Lleida, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Piñol-Ripoll
authors.affiliation: Neurology Division, Hospital Santa Maria of Lleida, E-25006 Lleida, Spain.
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Gil-Villar
authors.affiliation: Department of Basic Medical Sciences, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rué
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero-Otín
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, Department of Pathology and Experimental Therapeutics, University of Barcelona, E-08908, L'Hospitalet de Llobregat, Barcelona, Spain; Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), ISCIII, Spain. Electronic address: 8082ifa@gmail.com.
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain. Electronic address: reinald.pamplona@mex.udl.cat.
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000328:Adult; D001344:Autopsy; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002490:Central Nervous System / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D015227:Lipid Peroxidation; D008055:Lipids / Q000009:adverse effects / Q000302:isolation & purification*; D050155:Lipogenesis / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress
chemical_list: D005231:Fatty Acids, Unsaturated; D008055:Lipids; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human
keywords: Advanced lipoxidation end-products; Nrf2; Oxidative stress homeostasis; Peroxidizability index; Polyunsaturated fatty acid biosynthesis; Selective neuronal vulnerability