Cannabinoids modulate proliferation, differentiation, and migration signaling pathways in oligodendrocytes.
CB1
CB2
Cannabidiol
Endocannabinoids
Proteomics
Journal
European archives of psychiatry and clinical neuroscience
ISSN: 1433-8491
Titre abrégé: Eur Arch Psychiatry Clin Neurosci
Pays: Germany
ID NLM: 9103030
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
20
01
2022
accepted:
02
05
2022
pubmed:
28
5
2022
medline:
28
9
2022
entrez:
27
5
2022
Statut:
ppublish
Résumé
Cannabinoid signaling, mainly via CB1 and CB2 receptors, plays an essential role in oligodendrocyte health and functions. However, the specific molecular signals associated with the activation or blockade of CB1 and CB2 receptors in this glial cell have yet to be elucidated. Mass spectrometry-based shotgun proteomics and in silico biology tools were used to determine which signaling pathways and molecular mechanisms are triggered in a human oligodendrocytic cell line (MO3.13) by several pharmacological stimuli: the phytocannabinoid cannabidiol (CBD); CB1 and CB2 agonists ACEA, HU308, and WIN55, 212-2; CB1 and CB2 antagonists AM251 and AM630; and endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The modulation of cannabinoid signaling in MO3.13 was found to affect pathways linked to cell proliferation, migration, and differentiation of oligodendrocyte progenitor cells. Additionally, we found that carbohydrate and lipid metabolism, as well as mitochondrial function, were modulated by these compounds. Comparing the proteome changes and upstream regulators among treatments, the highest overlap was between the CB1 and CB2 antagonists, followed by overlaps between AEA and 2-AG. Our study opens new windows of opportunities, suggesting that cannabinoid signaling in oligodendrocytes might be relevant in the context of demyelinating and neurodegenerative diseases. Proteomics data are available at ProteomeXchange (PXD031923).
Identifiants
pubmed: 35622101
doi: 10.1007/s00406-022-01425-5
pii: 10.1007/s00406-022-01425-5
doi:
Substances chimiques
Cannabinoids
0
Carbohydrates
0
Endocannabinoids
0
Proteome
0
Cannabidiol
19GBJ60SN5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1311-1323Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
Références
Howlett AC (1985) Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes. Mol Pharmacol 27:429–436
pubmed: 2984538
Matsuda LA, Lolait SJ, Brownstein MJ et al (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564
pubmed: 2165569
Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65
pubmed: 7689702
Devane WA, Dysarz FA 3rd, Johnson MR et al (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605–613
pubmed: 2848184
Di Marzo V, Piscitelli F (2015) The endocannabinoid system and its modulation by phytocannabinoids. Neurotherapeutics 12:692–698
pubmed: 26271952
pmcid: 4604172
Howlett AC (1998) The CB1 cannabinoid receptor in the brain. Neurobiol Dis 5:405–416
pubmed: 9974174
Howlett AC, Abood ME (2017) CB and CB Receptor Pharmacology. Adv Pharmacol 80:169–206
pubmed: 28826534
pmcid: 5812699
Van Sickle MD, Duncan M, Kingsley PJ et al (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332
pubmed: 16224028
Lisboa SF, Gomes FV, Guimaraes FS, Campos AC (2016) Microglial Cells as a Link between Cannabinoids and the Immune Hypothesis of Psychiatric Disorders. Front Neurol 7:5
pubmed: 26858686
pmcid: 4729885
Rodrigues LCM, Gobira PH, de Oliveira AC et al (2014) Neuroinflammation as a possible link between cannabinoids and addiction. Acta Neuropsychiatr 26:334–346
pubmed: 25455257
Huerga-Gómez A, Aguado T, Sánchez-de la Torre A et al (2021) Δ -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo. Glia 69:532–545
pubmed: 32956517
de Almeida V, Martins-de-Souza D (2018) Cannabinoids and glial cells: possible mechanism to understand schizophrenia. Eur Arch Psychiatry Clin Neurosci 268:727–737
pubmed: 29392440
Katona I, Sperlágh B, Sı́k A, et al (1999) Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J Neurosci 19:4544–4558
pubmed: 10341254
pmcid: 6782612
Stella N (2010) Cannabinoid and cannabinoid-like receptors in microglia, astrocytes, and astrocytomas. Glia 58:1017–1030
pubmed: 20468046
pmcid: 2919281
Fünfschilling U, Supplie LM, Mahad D et al (2012) Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature 485:517–521
pubmed: 22622581
pmcid: 3613737
Lee Y, Morrison BM, Li Y et al (2012) Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature 487:443–448
pubmed: 22801498
pmcid: 3408792
Molina-Holgado E, Vela JM, Arévalo-Martín A et al (2002) Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J Neurosci 22:9742–9753
pubmed: 12427829
pmcid: 6757831
Solbrig MV, Fan Y, Hermanowicz N et al (2010) A synthetic cannabinoid agonist promotes oligodendrogliogenesis during viral encephalitis in rats. Exp Neurol 226:231–241
pubmed: 20832403
pmcid: 2981070
Gomez O, Sanchez-Rodriguez A, Le M et al (2011) Cannabinoid receptor agonists modulate oligodendrocyte differentiation by activating PI3K/Akt and the mammalian target of rapamycin (mTOR) pathways. Br J Pharmacol 163:1520–1532
pubmed: 21480865
pmcid: 3165960
Tomas-Roig J, Wirths O, Salinas-Riester G, Havemann-Reinecke U (2016) The cannabinoid CB1/CB2 agonist WIN55212.2 promotes oligodendrocyte differentiation in vitro and neuroprotection during the cuprizone-induced central nervous system demyelination. CNS Neurosci Ther 22:387–395
pubmed: 26842941
pmcid: 5067581
Moreno-Luna R, Esteban PF, Paniagua-Torija B et al (2021) Heterogeneity of the endocannabinoid system between cerebral cortex and spinal cord oligodendrocytes. Mol Neurobiol 58:689–702
pubmed: 33006124
Ilyasov AA, Milligan CE, Pharr EP, Howlett AC (2018) The Endocannabinoid system and oligodendrocytes in health and disease. Front Neurosci 12:733
pubmed: 30416422
pmcid: 6214135
Mecha M, Carrillo-Salinas FJ, Feliú A et al (2020) Perspectives on cannabis-based therapy of multiple sclerosis: a mini-review. Front Cell Neurosci 14:34
pubmed: 32140100
pmcid: 7042204
Jinsmaa Y, Isonaka R, Sharabi Y, Goldstein DS (2020) 3,4-Dihydroxyphenylacetaldehyde is more efficient than dopamine in oligomerizing and quinonizing -synuclein. J Pharmacol Exp Ther 372:157–165
pubmed: 31744850
pmcid: 6978699
Iwata K, Café-Mendes CC, Schmitt A et al (2013) The human oligodendrocyte proteome. Proteomics 13:3548–3553
pubmed: 24167090
Buntinx M, Vanderlocht J, Hellings N et al (2003) Characterization of three human oligodendroglial cell lines as a model to study oligodendrocyte injury: morphology and oligodendrocyte-specific gene expression. J Neurocytol 32:25–38
pubmed: 14618099
Brandão-Teles C, de Almeida V, Cassoli JS, Martins-de-Souza D (2019) Biochemical pathways triggered by antipsychotics in human [corrected] oligodendrocytes: potential of discovering new treatment targets. Front Pharmacol 10:186
pubmed: 30890939
pmcid: 6411851
Seabra G, de Almeida V, Reis-de-Oliveira G et al (2020) Ubiquitin-proteasome system, lipid metabolism and DNA damage repair are triggered by antipsychotic medication in human oligodendrocytes: implications in schizophrenia. Sci Rep 10:12655
pubmed: 32724114
pmcid: 7387551
Cassoli JS, Brandão-Teles C, Santana AG et al (2018) Ion mobility-enhanced data-independent acquisitions enable a deep proteomic landscape of oligodendrocytes. Proteomics. https://doi.org/10.1002/pmic.2018700015
doi: 10.1002/pmic.2018700015
pubmed: 29333719
Silva JC, Denny R, Dorschel CA et al (2005) Quantitative proteomic analysis by accurate mass retention time pairs. Anal Chem 77:2187–2200
pubmed: 15801753
Snel B, Lehmann G, Bork P, Huynen MA (2000) STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res 28:3442–3444
pubmed: 10982861
pmcid: 110752
Fabregat A, Sidiropoulos K, Garapati P et al (2016) The reactome pathway knowledgebase. Nucleic Acids Res 44:D481–D487
pubmed: 26656494
Uhlen M, Ponten F, Lindskog C (2015) Charting the human proteome: Understanding disease using a tissue-based atlas. Science 347:1274–1274
Yu G, Wang L-G, Han Y, He Q-Y (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16:284–287
pubmed: 22455463
pmcid: 3339379
Computing RFS (2013) R: A language and environment for statistical computing. R Core Team, Vienna
Tatomir A, Rao G, Boodhoo D et al (2020) Histone deacetylase SIRT1 mediates C5b-9-induced cell cycle in oligodendrocytes. Front Immunol 11:619
pubmed: 32328069
pmcid: 7160252
Prozorovski T, Ingwersen J, Lukas D et al (2019) Regulation of sirtuin expression in autoimmune neuroinflammation: Induction of SIRT1 in oligodendrocyte progenitor cells. Neurosci Lett 704:116–125
pubmed: 30953735
Hiratsuka D, Kurganov E, Furube E et al (2019) VEGF- and PDGF-dependent proliferation of oligodendrocyte progenitor cells in the medulla oblongata after LPC-induced focal demyelination. J Neuroimmunol 332:176–186
pubmed: 31075641
Mindos T, Dun X-P, North K et al (2017) Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity. J Cell Biol 216:495–510
pubmed: 28137778
pmcid: 5294779
Azevedo MM, Domingues HS, Cordelières FP et al (2018) Jmy regulates oligodendrocyte differentiation via modulation of actin cytoskeleton dynamics. Glia 66:1826–1844
pubmed: 29732611
Thomason EJ, Escalante M, Osterhout DJ, Fuss B (2019) The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination. Glia. https://doi.org/10.1002/glia.23735
doi: 10.1002/glia.23735
pubmed: 31696982
pmcid: 7942813
Nicaise AM, Johnson KM, Willis CM et al (2019) TIMP-1 promotes oligodendrocyte differentiation through receptor-mediated signaling. Mol Neurobiol 56:3380–3392
pubmed: 30121936
Harlow DE, Saul KE, Komuro H, Macklin WB (2015) Myelin proteolipid protein complexes with αv integrin and AMPA receptors In vivo and regulates ampa-dependent oligodendrocyte progenitor cell migration through the modulation of cell-surface GluR2 expression. J Neurosci 35:12018–12032
pubmed: 26311781
pmcid: 4549408
Linneberg C, Harboe M, Laursen LS (2015) Axo-glia interaction preceding CNS myelination is regulated by bidirectional eph-ephrin signaling. ASN Neuro. https://doi.org/10.1177/1759091415602859
doi: 10.1177/1759091415602859
pubmed: 26354550
pmcid: 4568937
Câmara J, Wang Z, Nunes-Fonseca C et al (2009) Integrin-mediated axoglial interactions initiate myelination in the central nervous system. J Cell Biol 185:699–712
pubmed: 19451276
pmcid: 2711572
Jagielska A, Lowe AL, Makhija E et al (2017) Mechanical strain promotes oligodendrocyte differentiation by global changes of gene expression. Front Cell Neurosci 11:93
pubmed: 28473753
pmcid: 5397481
Harboe M, Torvund-Jensen J, Kjaer-Sorensen K, Laursen LS (2018) Ephrin-A1-EphA4 signaling negatively regulates myelination in the central nervous system. Glia 66:934–950
pubmed: 29350423
Liang X, Draghi NA, Resh MD (2004) Signaling from integrins to Fyn to Rho family GTPases regulates morphologic differentiation of oligodendrocytes. J Neurosci 24:7140–7149
pubmed: 15306647
pmcid: 6729178
Ackerman SD, Garcia C, Piao X et al (2015) The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA. Nat Commun 6:6122
pubmed: 25607772
Thurnherr T, Benninger Y, Wu X et al (2006) Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS. J Neurosci 26:10110–10119
pubmed: 17021167
pmcid: 6674638
Seixas AI, Azevedo MM, Paes de Faria J et al (2019) Evolvability of the actin cytoskeleton in oligodendrocytes during central nervous system development and aging. Cell Mol Life Sci 76:1–11
pubmed: 30302529
Maki T, Choi YK, Miyamoto N et al (2018) A-kinase anchor protein 12 is required for oligodendrocyte differentiation in adult white matter. Stem Cells 36:751–760
pubmed: 29314444
Ghidinelli M, Poitelon Y, Shin YK et al (2017) Laminin 211 inhibits protein kinase A in Schwann cells to modulate neuregulin 1 type III-driven myelination. PLoS Biol 15:e2001408
pubmed: 28636612
pmcid: 5479503
Yang Y, Wang H, Zhang J et al (2013) Cyclin dependent kinase 5 is required for the normal development of oligodendrocytes and myelin formation. Dev Biol 378:94–106
pubmed: 23583582
pmcid: 3686511
Luo F, Burke K, Kantor C et al (2014) Cyclin-dependent kinase 5 mediates adult OPC maturation and myelin repair through modulation of Akt and GsK-3β signaling. J Neurosci 34:10415–10429
pubmed: 25080600
pmcid: 4115145
Miyamoto Y, Yamauchi J, Chan JR et al (2007) Cdk5 regulates differentiation of oligodendrocyte precursor cells through the direct phosphorylation of paxillin. J Cell Sci 120:4355–4366
pubmed: 18042622
Colognato H, Tzvetanova ID (2011) Glia unglued: how signals from the extracellular matrix regulate the development of myelinating glia. Dev Neurobiol 71:924–955
pubmed: 21834081
pmcid: 5679221
Hussain R, Macklin WB (2017) Integrin-linked kinase (ILK) deletion disrupts oligodendrocyte development by altering cell cycle. J Neurosci 37:397–412
pubmed: 28077718
pmcid: 5242396
Pronk JC, van Kollenburg B, Scheper GC, van der Knaap MS (2006) Vanishing white matter disease: a review with focus on its genetics. Ment Retard Dev Disabil Res Rev 12:123–128
pubmed: 16807905
Carter CJ (2007) eIF2B and oligodendrocyte survival: where nature and nurture meet in bipolar disorder and schizophrenia? Schizophr Bull 33:1343–1353
pubmed: 17329232
pmcid: 2779884
Arévalo-Martín A, García-Ovejero D, Rubio-Araiz A et al (2007) Cannabinoids modulate Olig2 and polysialylated neural cell adhesion molecule expression in the subventricular zone of post-natal rats through cannabinoid receptor 1 and cannabinoid receptor 2. Eur J Neurosci 26:1548–1559
pubmed: 17880390
Kuhn S, Gritti L, Crooks D, Dombrowski Y (2019) Oligodendrocytes in development, myelin generation and beyond. Cells. https://doi.org/10.3390/cells8111424
doi: 10.3390/cells8111424
pubmed: 31726662
pmcid: 6912544
Gaesser JM, Fyffe-Maricich SL (2016) Intracellular signaling pathway regulation of myelination and remyelination in the CNS. Exp Neurol 283:501–511
pubmed: 26957369
pmcid: 5010983
Bernal-Chico A, Canedo M, Manterola A et al (2015) Blockade of monoacylglycerol lipase inhibits oligodendrocyte excitotoxicity and prevents demyelination in vivo. Glia 63:163–176
pubmed: 25130621
Sanchez-Rodriguez MA, Gomez O, Esteban PF et al (2018) The endocannabinoid 2-arachidonoylglycerol regulates oligodendrocyte progenitor cell migration. Biochem Pharmacol 157:180–188
pubmed: 30195734
Nave K-A, Werner HB (2014) Myelination of the nervous system: mechanisms and functions. Annu Rev Cell Dev Biol 30:503–533
pubmed: 25288117
Hussain G, Wang J, Rasul A et al (2019) Role of cholesterol and sphingolipids in brain development and neurological diseases. Lipids Health Dis 18:26
pubmed: 30683111
pmcid: 6347843
Voskuhl RR, Itoh N, Tassoni A et al (2019) Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis. Proc Natl Acad Sci U S A 116:10130–10139
pubmed: 31040210
pmcid: 6525478
Lin J-P, Mironova YA, Shrager P, Giger RJ (2017) LRP1 regulates peroxisome biogenesis and cholesterol homeostasis in oligodendrocytes and is required for proper CNS myelin development and repair. Elife. https://doi.org/10.7554/eLife.30498
doi: 10.7554/eLife.30498
pubmed: 29251594
pmcid: 5752207
Oddi S, Caporali P, Dragotto J et al (2019) The endocannabinoid system is affected by cholesterol dyshomeostasis: Insights from a murine model of Niemann Pick type C disease. Neurobiol Dis 130:104531
pubmed: 31302243
Suo N, Guo Y-E, He B et al (2019) Inhibition of MAPK/ERK pathway promotes oligodendrocytes generation and recovery of demyelinating diseases. Glia 67:1320–1332
pubmed: 30815939
pmcid: 6593996
Wong YL, LeBon L, Basso AM et al (2019) eIF2B activator prevents neurological defects caused by a chronic integrated stress response. Elife. https://doi.org/10.7554/eLife.42940
doi: 10.7554/eLife.42940
pubmed: 31855181
pmcid: 6952179
Melas PA, Qvist JS, Deidda M et al (2018) Cannabinoid modulation of eukaryotic initiation factors (eIF2α and eIF2B1) and behavioral cross-sensitization to cocaine in adolescent rats. Cell Rep 22:2909–2923
pubmed: 29539420
Terumitsu-Tsujita M, Kitaura H, Miura I et al (2019) Glial pathology in a novel spontaneous mutant mouse of the Eif2b5 gene: a vanishing white matter disease model. J Neurochem. https://doi.org/10.1111/jnc.14887
doi: 10.1111/jnc.14887
pubmed: 31587290
Vrechi TA, Crunfli F, Costa AP, Torrão AS (2018) Cannabinoid receptor Type 1 Agonist ACEA protects neurons from death and attenuates endoplasmic reticulum stress-related apoptotic pathway signaling. Neurotox Res 33:846–855
pubmed: 29134561
Harris JJ, Attwell D (2012) The energetics of CNS white matter. J Neurosci 32:356–371
pubmed: 22219296
pmcid: 3272449
Rinholm JE, Vervaeke K, Tadross MR et al (2016) Movement and structure of mitochondria in oligodendrocytes and their myelin sheaths. Glia 64:810–825
pubmed: 26775288
Rao VTS, Khan D, Cui Q-L et al (2017) Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions. PLoS ONE 12:e0182372
pubmed: 28792512
pmcid: 5549710
Scarante FF, Ribeiro MA, Almeida-Santos AF et al (2020) Glial cells and their contribution to the mechanisms of action of cannabidiol in neuropsychiatric disorders. Front Pharmacol 11:618065
pubmed: 33613284
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 112:54–64
pubmed: 19447584
Morabito S, Miyoshi E, Michael N et al (2021) Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer’s disease. Nat Genet 53:1143–1155
pubmed: 34239132
pmcid: 8766217
Jäkel S, Agirre E, Mendanha Falcão A et al (2019) Altered human oligodendrocyte heterogeneity in multiple sclerosis. Nature 566:543–547
pubmed: 30747918
pmcid: 6544546
Osorio-Querejeta I, Sáenz-Cuesta M, Muñoz-Culla M, Otaegui D (2017) Models for studying myelination, demyelination and remyelination. Neuromolecular Med 19:181–192
pubmed: 28536996
Campos AC, Ortega Z, Palazuelos J et al (2013) The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system. Int J Neuropsychopharmacol 16:1407–1419
pubmed: 23298518
Levin R, Peres FF, Almeida V et al (2014) Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain. Front Pharmacol 5:10
pubmed: 24567721
pmcid: 3915876
Almeida V, Peres FF, Levin R et al (2014) Effects of cannabinoid and vanilloid drugs on positive and negative-like symptoms on an animal model of schizophrenia: The SHR strain. Schizophr Res 153:150–159
pubmed: 24556469
Almeida V, Levin R, Peres FF et al (2013) Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test. Prog Neuropsychopharmacol Biol Psychiatry 41:30–35
pubmed: 23127569
Gomez O, Sanchez-Rodriguez MA, Ortega-Gutierrez S et al (2015) A basal tone of 2-arachidonoylglycerol contributes to early oligodendrocyte progenitor proliferation by activating phosphatidylinositol 3-kinase (PI3K)/AKT and the mammalian target of rapamycin (MTOR) pathways. J Neuroimmune Pharmacol 10:309–317
pubmed: 25900077
Almeida V, Levin R, Peres FF et al (2019) Role of the endocannabinoid and endovanilloid systems in an animal model of schizophrenia-related emotional processing/cognitive deficit. Neuropharmacology 155:44–53
pubmed: 31103618
Perez-Riverol Y, Bai J, Bandla C et al (2022) The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res 50:D543–D552
pubmed: 34723319