Lipidome alterations in human prefrontal cortex during development, aging, and cognitive disorders.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
12
01
2018
accepted:
11
06
2018
revised:
26
04
2018
pubmed:
10
8
2018
medline:
16
3
2021
entrez:
10
8
2018
Statut:
ppublish
Résumé
Lipids are essential to brain functions, yet they remain largely unexplored. Here we investigated the lipidome composition of prefrontal cortex gray matter in 396 cognitively healthy individuals with ages spanning 100 years, as well as 67 adult individuals diagnosed with autism (ASD), schizophrenia (SZ), and Down syndrome (DS). Of the 5024 detected lipids, 95% showed significant age-dependent concentration differences clustering into four temporal stages, and resulting in a gradual increase in membrane fluidity in individuals ranging from newborn to nonagenarian. Aging affects 14% of the brain lipidome with late-life changes starting predominantly at 50-55 years of age-a period of general metabolic transition. All three diseases alter the brain lipidome composition, leading-among other things-to a concentration decrease in glycerophospholipid metabolism and endocannabinoid signaling pathways. Lipid concentration decreases in SZ were further linked to genetic variants associated with disease, indicating the relevance of the lipidome changes to disease progression.
Identifiants
pubmed: 30089790
doi: 10.1038/s41380-018-0200-8
pii: 10.1038/s41380-018-0200-8
pmc: PMC7577858
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2952-2969Références
Piomelli D, Astarita G, Rapaka R. A neuroscientist’s guide to lipidomics. Nat Rev Neurosci. 2007;8:743–54.
pubmed: 17882252
Lauwers E, Goodchild R, Verstreken P. Membrane lipids in presynaptic function and disease. Neuron. 2016;90:11–25.
pubmed: 27054615
Tau GZ, Peterson BS. Normal development of brain circuits. Neuropsychopharmacology. 2010;35:147–68.
pubmed: 19794405
Kostovic I, Judas M, Petanjek Z, Simic G. Ontogenesis of goal-directed behavior: anatomo-functional considerations. Int J Psychophysiol. 1995;19:85–102.
pubmed: 7622411
Burke SN, Barnes CA. Neural plasticity in the ageing brain. Nat Rev Neurosci. 2006;7:30–40.
pubmed: 16371948
Silbereis JC, Pochareddy S, Zhu Y, Li M, Sestan N. The cellular and molecular landscapes of the developing human central nervous system. Neuron. 2016;89:248–68.
pubmed: 26796689
pmcid: 4959909
Rouser G, Yamamoto A. Curvilinear regression course of human brain lipid composition changes with age. Lipids. 1968;3:284–7.
pubmed: 17805871
Soderberg M, Edlund C, Kristensson K, Dallner G. Lipid compositions of different regions of the human-brain during aging. J Neurochem. 1990;54:415–23.
pubmed: 2299344
Sakakihara Y, Volpe JJ. Dolichol in human brain: regional and developmental aspects. J Neurochem. 1985;44:1535–40.
pubmed: 3989548
Andersson M, Appelkvist EL, Kristensson K, Dallner G. Distribution of dolichol and dolichyl phosphate in human brain. J Neurochem. 1987;49:685–91.
pubmed: 3612118
Svennerholm L, Vanier MT, Jungbjer B. Changes in fatty acid composition of human brain myelin lipids during maturation. J Neurochem. 1978;30:1383–90.
pubmed: 670981
McNamara RK, Liu Y, Jandacek R, Rider T, Tso P. The aging human orbitofrontal cortex: decreasing polyunsaturated fatty acid composition and associated increases in lipogenic gene expression and stearoyl-CoA desaturase activity. Prostaglandins Leukot Essent Fat Acids. 2008;78:293–304.
Svennerholm L. Distribution and fatty acid composition of phosphoglycerides in normal human brain. J Lipid Res. 1968;9:570–9.
pubmed: 4302302
Pullarkat RK, Reha H. Accumulation of dolichols in brains of elderly. J Biol Chem. 1982;257:5991–3.
pubmed: 7076658
Svennerholm L, Bostrom K, Jungbjer B, Olsson L. Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J Neurochem. 1994;63:1802–11.
pubmed: 7931336
Martinez M, Mougan I. Fatty acid composition of human brain phospholipids during normal development. J Neurochem. 1998;71:2528–33.
pubmed: 9832152
Li Q, Bozek K, Xu C, Guo Y, Sun J, Paabo S, et al. Changes in lipidome composition during brain development in humans, chimpanzees, and macaque monkeys. Mol Biol Evol. 2017;34:1155–66.
pubmed: 28158622
pmcid: 5400384
Adelekan T, Magge S, Shults J, Stallings V, Stettler N. Lipid profiles of children with Down syndrome compared with their siblings. Pediatrics. 2012;129:e1382–87.
pubmed: 22585768
pmcid: 3362900
El-Ansary AK, Bacha AG, Al-Ayahdi LY. Plasma fatty acids as diagnostic markers in autistic patients from Saudi Arabia. Lipids Health Dis. 2011;10:62.
pubmed: 21510882
pmcid: 3107800
Kim EK, Neggers YH, Shin CS, Kim E, Kim EM. Alterations in lipid profile of autistic boys: a case control study. Nutr Res. 2010;30:255–60.
pubmed: 20534328
Kaddurah-Daouk R, McEvoy J, Baillie RA, Lee D, Yao JK, Doraiswamy PM, et al. Metabolomic mapping of atypical antipsychotic effects in schizophrenia. Mol Psychiatry. 2007;12:934–45.
pubmed: 17440431
McEvoy J, Baillie RA, Zhu H, Buckley P, Keshavan MS, Nasrallah HA, et al. Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics. PLoS ONE. 2013;8:e68717.
pubmed: 23894336
pmcid: 3722141
Oresic M, Seppanen-Laakso T, Sun D, Tang J, Therman S, Viehman R, et al. Phospholipids and insulin resistance in psychosis: a lipidomics study of twin pairs discordant for schizophrenia. Genome Med. 2012;4:1.
pubmed: 22257447
pmcid: 3334549
Solberg DK, Bentsen H, Refsum H, Andreassen OA. Lipid profiles in schizophrenia associated with clinical traits: a five year follow-up study. BMC Psychiatry. 2016;16:299.
pubmed: 27562545
pmcid: 5000423
Tessier C, Sweers K, Frajerman A, Bergaoui H, Ferreri F, Delva C, et al. Membrane lipidomics in schizophrenia patients: a correlational study with clinical and cognitive manifestations. Transl Psychiatry. 2016;6:e906.
pubmed: 27701405
pmcid: 5315538
Schwarz E, Prabakaran S, Whitfield P, Major H, Leweke FM, Koethe D, et al. High throughput lipidomic profiling of schizophrenia and bipolar disorder brain tissue reveals alterations of free fatty acids, phosphatidylcholines, and ceramides. J Proteome Res. 2008;7:4266–77.
pubmed: 18778095
Wood PL, Filiou MD, Otte DM, Zimmer A, Turck CW. Lipidomics reveals dysfunctional glycosynapses in schizophrenia and the G72/G30 transgenic mouse. Schizophr Res. 2014;159:365–9.
pubmed: 25263995
Brimacombe MB, Pickett R, Pickett J. Autism post-mortem neuroinformatic resource: the autism tissue program (ATP) informatics portal. J Autism Dev Disord. 2007;37:574–9.
pubmed: 16933088
Bozek K, Wei Y, Yan Z, Liu X, Xiong J, Sugimoto M, et al. Organization and evolution of brain lipidome revealed by large-scale analysis of human, chimpanzee, macaque, and mouse tissues. Neuron. 2015;85:695–702.
pubmed: 25661180
He Z, Bammann H, Han D, Xie G, Khaitovich P. Conserved expression of lincRNA during human and macaque prefrontal cortex development and maturation. RNA. 2014;20:1103–11.
pubmed: 24847104
pmcid: 4074677
Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015;12:357–60.
pubmed: 25751142
pmcid: 25751142
Anders S, Pyl PT, Huber W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31:166–9.
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.
pubmed: 25516281
pmcid: 25516281
Cheng C, Alexander R, Min R, Leng J, Yip KY, Rozowsky J, et al. Understanding transcriptional regulation by integrative analysis of transcription factor binding data. Genome Res. 2012;22:1658–67.
pubmed: 22955978
pmcid: 3431483
Somel M, Franz H, Yan Z, Lorenc A, Guo S, Giger T, et al. Transcriptional neoteny in the human brain. Proc Natl Acad Sci USA. 2009;106:5743–8.
pubmed: 19307592
Somel M, Guo S, Fu N, Yan Z, Hu HY, Xu Y, et al. MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res. 2010;20:1207–18.
pubmed: 20647238
pmcid: 2928499
Avanesov AS, Ma S, Pierce KA, Yim SH, Lee BC, Clish CB, et al. Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation. eLife. 2014;3:e02077.
pubmed: 24843015
pmcid: 4003482
Gladyshev VN. Aging: progressive decline in fitness due to the rising deleteriome adjusted by genetic, environmental, and stochastic processes. Aging Cell. 2016;15:594–602.
pubmed: 27060562
pmcid: 4933668
Lee SG, Kaya A, Avanesov AS, Podolskiy DI, Song EJ, Go DM, et al. Age-associated molecular changes are deleterious and may modulate life span through diet. Sci Adv. 2017;3:e1601833.
pubmed: 28232953
pmcid: 5315447
Liu X, Han D, Somel M, Jiang X, Hu H, Guijarro P, et al. Disruption of an evolutionarily novel synaptic expression pattern in autism. PLoS Biol. 2016;14:e1002558.
pubmed: 27685936
pmcid: 5042529
Leslie R, O’Donnell CJ, Johnson AD. GRASP: analysis of genotype-phenotype results from 1390 genome-wide association studies and corresponding open access database. Bioinformatics. 2014;30:i185–94.
pubmed: 24931982
pmcid: 4072913
Wu Y, Yao YG, Luo XJ. SZDB: a database for schizophrenia genetic research. Schizophr Bull. 2017;43:459–71.
pubmed: 27451428
Gennis RB. Biomembranes: molecular structure and function. 1989 edn. Springer: Berlin, 1988. 533pp.
Heimburg T. Thermal biophysics of membranes. 1 edn. Wiley-VCH: Weinheim, 2007. 378pp.
Bozek K, Khrameeva EE, Reznick J, Omerbasic D, Bennett NC, Lewin GR, et al. Lipidome determinants of maximal lifespan in mammals. Sci Rep. 2017;7:5.
pubmed: 28127055
pmcid: 5428381
Huttenlocher PR, Dabholkar AS. Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol. 1997;387:167–78.
pubmed: 9336221
Petanjek Z, Judas M, Simic G, Rasin MR, Uylings HB, Rakic P, et al. Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proc Natl Acad Sci USA. 2011;108:13281–6.
pubmed: 21788513
Miller DJ, Duka T, Stimpson CD, Schapiro SJ, Baze WB, McArthur MJ, et al. Prolonged myelination in human neocortical evolution. Proc Natl Acad Sci USA. 2012;109:16480–5.
pubmed: 23012402
Liu X, Somel M, Tang L, Yan Z, Jiang X, Guo S, et al. Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques. Genome Res. 2012;22:611–22.
pubmed: 22300767
pmcid: 3317144
Rakic P, Bourgeois JP, Eckenhoff MF, Zecevic N, Goldman-Rakic PS. Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science. 1986;232:232–5.
pubmed: 3952506
Sineriz F, Bloj B, Farias RN, Trucco RE. Regulation by membrane fluidity of the allosteric behavior of the (Ca2)-adenosine triphosphatase from Escherichia coli. J Bacteriol. 1973;115:723–6.
pubmed: 4269584
pmcid: 246313
Nicolson GL. The fluid-mosaic model of membrane structure: still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years. Biochim Et Biophys Acta-Biomembr. 2014;1838:1451–66.
Noutsi P, Gratton E, Chaieb S. Assessment of membrane fluidity fluctuations during cellular development reveals time and cell type specificity. PLoS ONE. 2016;11:e0158313.
pubmed: 27362860
pmcid: 4928918
Rattan SIS. Increased molecular damage and heterogeneity as the basis of aging. Biol Chem. 2008;389:267–72.
pubmed: 18208348
Lombard DB, Chua KF, Mostoslavsky R, Franco S, Gostissa M, Alt FW. DNA repair, genome stability, and aging. Cell. 2005;120:497–512.
pubmed: 15734682
Bahar R, Hartmann CH, Rodriguez KA, Denny AD, Busuttil RA, Dolle MET, et al. Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature. 2006;441:1011–4.
pubmed: 16791200
Paus T, Collins DL, Evans AC, Leonard G, Pike B, Zijdenbos A. Maturation of white matter in the human brain: a review of magnetic resonance studies. Brain Res Bull. 2001;54:255–66.
pubmed: 11287130
Speakman JR, Westerterp KR. Associations between energy demands, physical activity, and body composition in adult humans between 18 and 96 y of age. Am J Clin Nutr. 2010;92:826–34.
pubmed: 20810973
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153:1194–217.
pubmed: 3836174
pmcid: 3836174
St-Onge MP. Relationship between body composition changes and changes in physical function and metabolic risk factors in aging. Curr Opin Clin Nutr Metab Care. 2005;8:523–8.
pubmed: 16079623
pmcid: 16079623
St-Onge MP, Gallagher D. Body composition changes with aging: the cause or the result of alterations in metabolic rate and macronutrient oxidation? Nutrition. 2010;26:152–5.
pubmed: 20004080
Sethi S, Hayashi MA, Barbosa BS, Pontes JG, Tasic L, Brietzke E. Lipidomics, biomarkers, and schizophrenia: a current perspective. Adv Exp Med Biol. 2017;965:265–90.
pubmed: 28132184
Chung KH, Tsai SY, Lee HC. Mood symptoms and serum lipids in acute phase of bipolar disorder in Taiwan. Psychiatry Clin Neurosci. 2007;61:428–33.
pubmed: 17610669
Chan RB, Oliveira TG, Cortes EP, Honig LS, Duff KE, Small SA, et al. Comparative lipidomic analysis of mouse and human brain with Alzheimer disease. J Biol Chem. 2012;287:2678–88.
pubmed: 22134919
Karhson DS, Hardan AY, Parker KJ. Endocannabinoid signaling in social functioning: an RDoC perspective. Transl Psychiatry. 2016;6:e905.
pubmed: 27676446
pmcid: 5048207
Wei D, Allsop S, Tye K, Piomelli D. Endocannabinoid signaling in the control of social behavior. Trends Neurosci. 2017;40:385–96.
pubmed: 28554687
pmcid: 5699224
Eggan SM, Hashimoto T, Lewis DA. Reduced cortical cannabinoid 1 receptor messenger RNA and protein expression in schizophrenia. Arch Gen Psychiatry. 2008;65:772–84.
pubmed: 18606950
pmcid: 2890225
Muguruza C, Lehtonen M, Aaltonen N, Morentin B, Meana JJ, Callado LF. Quantification of endocannabinoids in postmortem brain of schizophrenic subjects. Schizophr Res. 2013;148:145–50.
pubmed: 23800614
Chakrabarti B, Persico A, Battista N, Maccarrone M. Endocannabinoid signaling in autism. Neurotherapeutics. 2015;12:837–47.
pubmed: 26216231
pmcid: 4604173
Pazos MR, Sagredo O, Fernandez-Ruiz J. The endocannabinoid system in Huntington’s disease. Curr Pharm Des. 2008;14:2317–25.
pubmed: 18781982
Berger GE, Smesny S, Amminger GP. Bioactive lipids in schizophrenia. Int Rev Psychiatry. 2006;18:85–98.
pubmed: 16777663
Schmitt A, Wilczek K, Blennow K, Maras A, Jatzko A, Petroianu G, et al. Altered thalamic membrane phospholipids in schizophrenia: a postmortem study. Biol Psychiatry. 2004;56:41–45.
pubmed: 15219471
Chang SH, Chiang SY, Chiu CC, Tsai CC, Tsai HH, Huang CY, et al. Expression of anti-cardiolipin antibodies and inflammatory associated factors in patients with schizophrenia. Psychiatry Res. 2011;187:341–6.
pubmed: 20510460
Careaga M, Hansen RL, Hertz-Piccotto I, Van de Water J, Ashwood P. Increased anti-phospholipid antibodies in autism spectrum disorders. Mediat Inflamm. 2013;2013:935608.
Helguera P, Seiglie J, Rodriguez J, Hanna M, Helguera G, Busciglio J. Adaptive downregulation of mitochondrial function in down syndrome. Cell Metab. 2013;17:132–40.
pubmed: 23312288
pmcid: 3580189
Brindley DN. Metabolism of triacylglycerols. In: Vance DE, Vance J (eds). Biochemistry of lipids, lipoproteins and membranes. Elsevier Science: New York, 1991.
Perez-Rodriguez L, Romero-Haro AA, Sternalski A, Muriel J, Mougeot F, Gil D, et al. Measuring oxidative stress: the confounding effect of lipid concentration in measures of lipid peroxidation. Physiol Biochem Zool. 2015;88:345–51.
pubmed: 25860832
Walsh CA, Morrow EM, Rubenstein JLR. Autism and brain development. Cell. 2008;135:396–400.
pubmed: 18984148
pmcid: 2701104
Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 1987;44:660–9.
pubmed: 3606332
Becker L, Mito T, Takashima S, Onodera K. Growth and development of the brain in Down syndrome. Prog Clin Biol Res. 1991;373:133–52.
pubmed: 1838182
Olmos-Serrano JL, Kang HJ, Tyler WA, Silbereis JC, Cheng F, Zhu Y, et al. Down syndrome developmental brain transcriptome reveals defective oligodendrocyte differentiation and myelination. Neuron. 2016;89:1208–22.
pubmed: 26924435
pmcid: 4795969
Kirkpatrick B, Messias E, Harvey PD, Fernandez-Egea E, Bowie CR. Is schizophrenia a syndrome of accelerated aging? Schizophr Bull. 2008;34:1024–32.
pubmed: 18156637
Schnack HG, van Haren NE, Nieuwenhuis M, Hulshoff Pol HE, Cahn W, Kahn RS. Accelerated brain aging in schizophrenia: a longitudinal pattern recognition study. Am J Psychiatry. 2016;173:607–16.
pubmed: 26917166
Rahman NA. A course in theoretical statistics. Charles Griffin & Company Limited: Glasgow, 1968.