Analysis of circulating exosomes reveals a peripheral signature of astrocytic pathology in schizophrenia

References

• Amberger JS, Bocchini CA, Schiettecatte F, Scott AF, Hamosh A. 2015. OMIM.org: Online Mendelian Inheritance in Man (OMIM(R)), an online catalog of human genes and genetic disorders. Nucleic Acids Res. 43(Database issue):D789–98.
   PubMed Web of Science ®Google Scholar
• Amberger JS, Bocchini CA, Scott AF, Hamosh A. 2019. OMIM.org: leveraging knowledge across phenotype-gene relationships. Nucleic Acids Res. 47(D1):D1038–D1043.
   PubMed Web of Science ®Google Scholar
• Amoah SK, Rodriguez BA, Logothetis CN, Chander P, Sellgren CM, Weick JP, Sheridan SD, Jantzie LL, Webster MJ, Mellios N. 2020. Exosomal secretion of a psychosis-altered miRNA that regulates glutamate receptor expression is affected by antipsychotics. Neuropsychopharmacology. 45:656–665.
   PubMed Web of Science ®Google Scholar
• Banigan MG, Kao PF, Kozubek JA, Winslow AR, Medina J, Costa J, Schmitt A, Schneider A, Cabral H, Cagsal-Getkin O, et al. 2013. Differential expression of exosomal microRNAs in prefrontal cortices of schizophrenia and bipolar disorder patients. PLOS One. 8(1):e48814.
   PubMed Web of Science ®Google Scholar
• Barley K, Dracheva S, Byne W. 2009. Subcortical oligodendrocyte- and astrocyte-associated gene expression in subjects with schizophrenia, major depression and bipolar disorder. Schizophr Res. 112(1–3):54–64.
   PubMed Web of Science ®Google Scholar
• Boesmans W, Ameloot K, van den Abbeel V, Tack J, Vanden Berghe P. 2009. Cannabinoid receptor 1 signalling dampens activity and mitochondrial transport in networks of enteric neurones. Neurogastroenterol Motil. 21(9):958–e77.
   PubMed Web of Science ®Google Scholar
• Catts VS, Wong J, Fillman SG, Fung SJ, Shannon Weickert C. 2014. Increased expression of astrocyte markers in schizophrenia: association with neuroinflammation. Aust N Z J Psychiatry. 48(8):722–734.
   PubMed Web of Science ®Google Scholar
• Ceylan D, Tufekci KU, Keskinoglu P, Genc S, Ozerdem A. 2020. Circulating exosomal microRNAs in bipolar disorder. J Affect Disord. 262:99–107.
   PubMed Web of Science ®Google Scholar
• Colombo M, Raposo G, Thery C. 2014. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 30:255–289.
   PubMed Web of Science ®Google Scholar
• da Silva VK, de Freitas BS, da Silva Dornelles A, Nery LR, Falavigna L, Ferreira RD, Bogo MR, Hallak JE, Zuardi AW, Crippa JA, et al. 2014. Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection. Mol Neurobiol. 49(1):222–233.
   PubMed Web of Science ®Google Scholar
• Dietz AG, Goldman SA, Nedergaard M. 2020. Glial cells in schizophrenia: a unified hypothesis. Lancet Psychiat. 7(3):272–281.
   PubMed Web of Science ®Google Scholar
• Du Y, Yu Y, Hu Y, Li XW, Wei ZX, Pan RY, Li XS, Zheng GE, Qin XY, Liu QS, et al. 2019. Genome-wide, integrative analysis implicates exosome-derived microRNA dysregulation in schizophrenia. Schizophr Bull. 45(6):1257–1266.
   PubMed Web of Science ®Google Scholar
• Egbujo CN, Sinclair D, Hahn CG. 2016. Dysregulations of synaptic vesicle trafficking in schizophrenia. Curr Psychiatry Rep. 18(8):77.
   PubMed Web of Science ®Google Scholar
• Farnsworth B, Radomska KJ, Zimmermann B, Kettunen P, Jazin E, Emilsson LS. 2017. QKI6B mRNA levels are upregulated in schizophrenia and predict GFAP expression. Brain Res. 1669:63–68.
   PubMed Web of Science ®Google Scholar
• Farnsworth DL. 1976. What is the evidence for an amotivational syndrome in cannabis users? Ann N Y Acad Sci. 282:1.
   PubMed Web of Science ®Google Scholar
• Feresten AH, Barakauskas V, Ypsilanti A, Barr AM, Beasley CL. 2013. Increased expression of glial fibrillary acidic protein in prefrontal cortex in psychotic illness. Schizophr Res. 150(1):252–257.
   PubMed Web of Science ®Google Scholar
• Fries GR, Lima CNC, Valvassori SS, Zunta-Soares G, Soares JC, Quevedo J. 2019. Preliminary investigation of peripheral extracellular vesicles' microRNAs in bipolar disorder. J Affect Disord. 255:10–14.
   PubMed Web of Science ®Google Scholar
• Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Petersen RC, Miller BL, Kapogiannis D. 2015. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology. 85(1):40–47.
   PubMed Web of Science ®Google Scholar
• Goetzl EJ, Elahi FM, Mustapic M, Kapogiannis D, Pryhoda M, Gilmore A, Gorgens KA, Davidson B, Granholm AC, Ledreux A. 2019. Altered levels of plasma neuron-derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury. FASEB J. 33(4):5082–5088.
   PubMed Web of Science ®Google Scholar
• Goetzl EJ, Kapogiannis D, Schwartz JB, Lobach IV, Goetzl L, Abner EL, Jicha GA, Karydas AM, Boxer A, Miller BL. 2016. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease. FASEB J. 30(12):4141–4148.
   PubMed Web of Science ®Google Scholar
• Goetzl EJ, Mustapic M, Kapogiannis D, Eitan E, Lobach IV, Goetzl L, Schwartz JB, Miller BL. 2016. Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease. FASEB J. 30(11):3853–3859.
   PubMed Web of Science ®Google Scholar
• Goetzl EJ, Schwartz JB, Abner EL, Jicha GA, Kapogiannis D. 2018. High complement levels in astrocyte-derived exosomes of Alzheimer disease. Ann Neurol. 83(3):544–552.
   PubMed Web of Science ®Google Scholar
• Goetzl EJ, Srihari VH, Guloksuz S, Ferrara M, Tek C, Heninger GR. 2020. Decreased mitochondrial electron transport proteins and increased complement mediators in plasma neural-derived exosomes of early psychosis. Transl Psychiatry. 10(1):361.
   PubMed Web of Science ®Google Scholar
• Gruzdev SK, Yakovlev AA, Druzhkova TA, Guekht AB, Gulyaeva NV. 2019. The missing link: how exosomes and miRNAs can help in bridging psychiatry and molecular biology in the context of depression, bipolar disorder and schizophrenia. Cell Mol Neurobiol. 39(6):729–750.
   PubMed Web of Science ®Google Scholar
• Gunasekaran M, Xu Z, Nayak DK, Sharma M, Hachem R, Walia R, Bremner RM, Smith MA, Mohanakumar T. 2017. Donor-Derived exosomes with lung self-antigens in human lung allograft rejection. Am J Transplant. 17(2):474–484.
   PubMed Web of Science ®Google Scholar
• Hadley Wickham MA, Bryan J, Chang W, McGowan L, François R, Grolemund G, Hayes A, Henry L, Hester J, Kuhn M, et al. 2019. Welcome to the {tidyverse}. J Open Source Software. 4:1686.
   Google Scholar
• Kahn RS, Sommer IE, Murray RM, Meyer-Lindenberg A, Weinberger DR, Cannon TD, O'Donovan M, Correll CU, Kane JM, van Os J, et al. 2015. Schizophrenia. Nat Rev Dis Primers. 1:15067.
   PubMed Web of Science ®Google Scholar
• Kapogiannis D, Dobrowolny H, Tran J, Mustapic M, Frodl T, Meyer-Lotz G, Schiltz K, Schanze D, Rietschel M, Bernstein HG, et al. 2019. Insulin-signaling abnormalities in drug-naive first-episode schizophrenia: transduction protein analyses in extracellular vesicles of putative neuronal origin. Eur Psychiatry. 62:124–129.
   PubMed Web of Science ®Google Scholar
• Karnati HK, Garcia JH, Tweedie D, Becker RE, Kapogiannis D, Greig NH. 2019. Neuronal enriched extracellular vesicle proteins as biomarkers for traumatic brain injury. J Neurotrauma. 36(7):975–987.
   PubMed Web of Science ®Google Scholar
• Kassambara A. 2020. ggpubr: 'ggplot2' Based Publication Ready Plots. 0.4.0 ed. https://cran.r-project.org/web/packages/ggpubr/index.html
   Google Scholar
• Kim R, Healey KL, Sepulveda-Orengo MT, Reissner KJ. 2018. Astroglial correlates of neuropsychiatric disease: from astrocytopathy to astrogliosis. Prog Neuropsychopharmacol Biol Psychiatry. 87(Pt A):126–146.
   PubMedGoogle Scholar
• Kwon SE, Chapman ER. 2011. Synaptophysin regulates the kinetics of synaptic vesicle endocytosis in central neurons. Neuron. 70(5):847–854.
   PubMed Web of Science ®Google Scholar
• Laskaris LE, Di Biase MA, Everall I, Chana G, Christopoulos A, Skafidas E, Cropley VL, Pantelis C. 2016. Microglial activation and progressive brain changes in schizophrenia. Br J Pharmacol. 173(4):666–680.
   PubMed Web of Science ®Google Scholar
• Lee Y, El Andaloussi S, Wood MJA. 2012. Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Human Mol Genet. 21(R1):R125–R134.
   PubMed Web of Science ®Google Scholar
• Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. 2005. What does the PANSS mean? Schizophr Res. 79(2–3):231–238.
   PubMed Web of Science ®Google Scholar
• Leucht S, Samara M, Heres S, Davis JM. 2016. Dose equivalents for antipsychotic drugs: the DDD method. Schizophr Bull. 42(Suppl 1):S90–S4.
   PubMedGoogle Scholar
• Levy E. 2017. Exosomes in the diseased brain: first insights from in vivo studies. Front Neurosci. 11:142.
   PubMed Web of Science ®Google Scholar
• Lewis SB, Velat GJ, Miralia L, Papa L, Aikman JM, Wolper RA, Firment CS, Liu MC, Pineda JA, Wang KK, et al. 2007. Alpha-II spectrin breakdown products in aneurysmal subarachnoid hemorrhage: a novel biomarker of proteolytic injury. J Neurosurg. 107(4):792–796.
   PubMed Web of Science ®Google Scholar
• Mager I. 2020. Extracellular vesicles in neurodegenerative disorders. In: Edelstein LS, Jr.; Quesenberry PJ; Noble D, editors. Exosomes: a clinical compendium. London; Oxford; San Diego, CA; Cambridge, MA: Elsevier.
   Google Scholar
• Manek R, Moghieb A, Yang Z, Kumar D, Kobessiy F, Sarkis GA, Raghavan V, Wang KKW. 2018. Protein biomarkers and neuroproteomics characterization of microvesicles/exosomes from human cerebrospinal fluid following traumatic brain injury. Mol Neurobiol. 55(7):6112–6128.
   PubMed Web of Science ®Google Scholar
• Osimo EF, Beck K, Reis Marques T, Howes OD. 2019. Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures. Mol Psychiatry. 24(4):549–561.
   PubMed Web of Science ®Google Scholar
• Pineda JA, Lewis SB, Valadka AB, Papa L, Hannay HJ, Heaton SC, Demery JA, Liu MC, Aikman JM, Akle V, et al. 2007. Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury. J Neurotrauma. 24(2):354–366.
   PubMed Web of Science ®Google Scholar
• R Development Core Team. 2019. R: a language and environment for statistical computing. 3.6.1. Vienna, Austria: R Foundation for Statistical Computing.
   Google Scholar
• Reyes R, Cardeñes B, Machado-Pineda Y, Cabañas C. 2018. Tetraspanin CD9: a key regulator of cell adhesion in the immune system. Front Immunol. 9:863.
   PubMed Web of Science ®Google Scholar
• Robinson SM, Sobell LC, Sobell MB, Leo GI. 2014. Reliability of the timeline followback for cocaine, cannabis, and cigarette use. Psychol Addict Behav. 28(1):154–162.
   PubMed Web of Science ®Google Scholar
• Rosengren LE, Wikkelso C, Hagberg L. 1994. A sensitive ELISA for glial fibrillary acidic protein: application in CSF of adults. J Neurosci Methods. 51(2):197–204.
   PubMed Web of Science ®Google Scholar
• Saeedi S, Israel S, Nagy C, Turecki G. 2019. The emerging role of exosomes in mental disorders. Transl Psychiatry. 9(1):122.
   PubMed Web of Science ®Google Scholar
• Sales AJ, Fogaca MV, Sartim AG, Pereira VS, Wegener G, Guimaraes FS, Joca SRL. 2019. Cannabidiol induces rapid and sustained antidepressant-like effects through increased BDNF signaling and synaptogenesis in the prefrontal cortex. Mol Neurobiol. 56(2):1070–1081.
   PubMed Web of Science ®Google Scholar
• Soares Martins T, Catita J, Martins Rosa I, ABdCES O, Henriques AG. 2018. Exosome isolation from distinct biofluids using precipitation and column-based approaches. PLoS One. 13(6):e0198820.
   PubMed Web of Science ®Google Scholar
• Stahl PD, Raposo G. 2019. Extracellular vesicles: exosomes and microvesicles, integrators of homeostasis. Physiology. 34(3):169–177.
   PubMed Web of Science ®Google Scholar
• Steffek AE, McCullumsmith RE, Haroutunian V, Meador-Woodruff JH. 2008. Cortical expression of glial fibrillary acidic protein and glutamine synthetase is decreased in schizophrenia. Schizophr Res. 103(1–3):71–82.
   PubMed Web of Science ®Google Scholar
• Steiner J, Bielau H, Bernstein HG, Bogerts B, Wunderlich MT. 2006. Increased cerebrospinal fluid and serum levels of S100B in first-onset schizophrenia are not related to a degenerative release of glial fibrillar acidic protein, myelin basic protein and neurone-specific enolase from glia or neurones. J Neurol Neurosurg Psychiatry. 77(11):1284–1287.
   PubMed Web of Science ®Google Scholar
• Sun B, Dalvi P, Abadjian L, Tang N, Pulliam L. 2017. Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV. AIDS. 31(14):F9–F17.
   PubMed Web of Science ®Google Scholar
• Tan G, Wang L, Liu Y, Zhang H, Feng W, Liu Z. 2021. The alterations of circular RNA expression in plasma exosomes from patients with schizophrenia. J Cell Physiol. 236(1):458–467.
   Web of Science ®Google Scholar
• Thery C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK, et al. 2018. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 7(1):1535750.
   PubMed Web of Science ®Google Scholar
• Toro CT, Hallak JE, Dunham JS, Deakin JF. 2006. Glial fibrillary acidic protein and glutamine synthetase in subregions of prefrontal cortex in schizophrenia and mood disorder. Neurosci Lett. 404(3):276–281.
   PubMed Web of Science ®Google Scholar
• Wei ZX, Xie GJ, Mao X, Zou XP, Liao YJ, Liu QS, Wang H, Cheng Y. 2020. Exosomes from patients with major depression cause depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis. Neuropsychopharmacology. 45(6):1050–1058.
   PubMed Web of Science ®Google Scholar
• Williams DB. 2006. Beyond lectins: the calnexin/calreticulin chaperone system of the endoplasmic reticulum. J Cell Sci. 119(Pt 4):615–623.
   PubMed Web of Science ®Google Scholar
• Winston CN, Goetzl EJ, Schwartz JB, Elahi FM, Rissman RA. 2019. Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia. Alzheimers Dement. 11:61–66.
   Web of Science ®Google Scholar
• Xu C, Chang T, Du Y, Yu C, Tan X, Li X. 2019. Pharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model. Environ Toxicol Pharmacol. 70:103202.
   PubMed Web of Science ®Google Scholar
• Yang Z, Wang KK. 2015. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci. 38(6):364–374.
   PubMed Web of Science ®Google Scholar
• Yu LL, Zhu J, Liu JX, Jiang F, Ni WK, Qu LS, Ni RZ, Lu CH, Xiao MB. 2018. A comparison of traditional and novel methods for the separation of exosomes from human samples. Biomed Res Int. 2018:3634563.
   PubMed Web of Science ®Google Scholar