Skip to main content

Advertisement

SpringerLink
Log in

Olfactory Neuroepithelium Cells from Cannabis Users Display Alterations to the Cytoskeleton and to Markers of Adhesion, Proliferation and Apoptosis

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Cannabis is the third most commonly used psychoactive substance of abuse, yet it also receives considerable attention as a potential therapeutic drug. Therefore, it is essential to fully understand the actions of cannabis in the human brain. The olfactory neuroepithelium (ON) is a peripheral nervous tissue that represents an interesting surrogate model to study the effects of drugs in the brain, since it is closely related to the central nervous system, and sensory olfactory neurons are continually regenerated from populations of stem/progenitor cells that undergo neurogenesis throughout life. In this study, we used ON cells from chronic cannabis users and healthy control subjects to assess alterations in relevant cellular processes, and to identify changes in functional proteomic pathways due to cannabis consumption. The ON cells from cannabis users exhibited alterations in the expression of proteins that were related to the cytoskeleton, cell proliferation and cell death, as well as, changes in proteins implicated in cancer, gastrointestinal and neurodevelopmental pathologies. Subsequent studies showed cannabis provoked an increase in cell size and morphological alterations evident through β-Tubulin III staining, as well as, enhanced beta-actin expression and a decrease in the ability of ON cells to undergo cell attachment, suggesting abnormalities of the cytoskeleton and cell adhesion system. Furthermore, these cells proliferated more and underwent less cell death. Our results indicate that cannabis may alter key processes of the developing brain, some of which are similar to those reported in mental disorders like DiGeorge syndrome, schizophrenia and bipolar disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

This Declaration acknowledges that this paper adheres to the principles for transparent reporting and scientific rigour of preclinical research as stated in the BJP guidelines for Design and Analysis, Immunoblotting and Immunochemistry, and as recommended by funding agencies, publishers and other organisations engaged with supporting research.

References

  1. Campeny E, Lopez-Pelayo H, Nutt D, Blithikioti C, Oliveras C, Nuno L, Maldonado R, Florez G et al (2020) The blind men and the elephant: systematic review of systematic reviews of cannabis use related health harms. Eur Neuropsychopharmacol 33:1–35. https://doi.org/10.1016/j.euroneuro.2020.02.003

    Article  CAS  PubMed  Google Scholar 

  2. Maccarrone M, Maldonado R, Casas M, Henze T, Centonze D (2017) Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others? Expert Rev Clin Pharmacol 10(4):443–455. https://doi.org/10.1080/17512433.2017.1292849

    Article  CAS  PubMed  Google Scholar 

  3. Bloomfield MAP, Hindocha C, Green SF, Wall MB, Lees R, Petrilli K, Costello H, Ogunbiyi MO et al (2019) The neuropsychopharmacology of cannabis: a review of human imaging studies. Pharmacol Ther 195:132–161. https://doi.org/10.1016/j.pharmthera.2018.10.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Szutorisz H, Hurd YL (2016) Epigenetic effects of cannabis exposure. Biol Psychiatry 79(7):586–594. https://doi.org/10.1016/j.biopsych.2015.09.014

    Article  CAS  PubMed  Google Scholar 

  5. Leung CT, Coulombe PA, Reed RR (2007) Contribution of olfactory neural stem cells to tissue maintenance and regeneration. Nat Neurosci 10(6):720–726. https://doi.org/10.1038/nn1882

    Article  CAS  PubMed  Google Scholar 

  6. Matigian N, Abrahamsen G, Sutharsan R, Cook AL, Vitale AM, Nouwens A, Bellette B, An J et al (2010) Disease-specific, neurosphere-derived cells as models for brain disorders. Dis Model Mech 3(11–12):785–798. https://doi.org/10.1242/dmm.005447

    Article  CAS  PubMed  Google Scholar 

  7. Feron F, Perry C, Hirning MH, McGrath J, Mackay-Sim A (1999) Altered adhesion, proliferation and death in neural cultures from adults with schizophrenia. Schizophr Res 40(3):211–218. https://doi.org/10.1016/s0920-9964(99)00055-9

    Article  CAS  PubMed  Google Scholar 

  8. McCurdy RD, Feron F, Perry C, Chant DC, McLean D, Matigian N, Hayward NK, McGrath JJ et al (2006) Cell cycle alterations in biopsied olfactory neuroepithelium in schizophrenia and bipolar I disorder using cell culture and gene expression analyses. Schizophr Res 82(2–3):163–173. https://doi.org/10.1016/j.schres.2005.10.012

    Article  PubMed  Google Scholar 

  9. Solis-Chagoyan H, Calixto E, Figueroa A, Montano LM, Berlanga C, Rodriguez-Verdugo MS, Romo F, Jimenez M et al (2013) Microtubule organization and L-type voltage-activated calcium current in olfactory neuronal cells obtained from patients with schizophrenia and bipolar disorder. Schizophr Res 143(2–3):384–389. https://doi.org/10.1016/j.schres.2012.11.035

    Article  CAS  PubMed  Google Scholar 

  10. Munoz-Estrada J, Benitez-King G, Berlanga C, Meza I (2015) Altered subcellular distribution of the 75-kDa DISC1 isoform, cAMP accumulation, and decreased neuronal migration in schizophrenia and bipolar disorder: implications for neurodevelopment. CNS Neurosci Ther 21(5):446–453. https://doi.org/10.1111/cns.12377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Galindo L, Moreno E, Lopez-Armenta F, Guinart D, Cuenca-Royo A, Izquierdo-Serra M, Xicota L, Fernandez C et al (2018) Cannabis users show enhanced expression of CB1-5HT2A receptor heteromers in olfactory neuroepithelium cells. Mol Neurobiol 55(8):6347–6361. https://doi.org/10.1007/s12035-017-0833-7

    Article  CAS  PubMed  Google Scholar 

  12. Saladrigas-Manjon S, Ducic T, Galindo L, Fernandez-Aviles C, Perez V, de la Torre R, Robledo P (2020) Effects of cannabis use on the protein and lipid profile of olfactory neuroepithelium cells from schizophrenia patients studied by synchrotron-based FTIR spectroscopy. Biomolecules 10(2). https://doi.org/10.3390/biom10020329

  13. Buchanan JT, Grillner S, Cullheim S, Risling M (1989) Identification of excitatory interneurons contributing to generation of locomotion in lamprey: structure, pharmacology, and function. J Neurophysiol 62(1):59–69. https://doi.org/10.1152/jn.1989.62.1.59

    Article  CAS  PubMed  Google Scholar 

  14. Endicott J, Spitzer RL, Fleiss JL, Cohen J (1976) The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry 33(6):766–771. https://doi.org/10.1001/archpsyc.1976.01770060086012

    Article  CAS  PubMed  Google Scholar 

  15. Wechsler D (1997) Wechsler Adult Intelligence Scale. The Psychological Corporation, Third Edition edn San Antonio, TX

    Google Scholar 

  16. Benton AL (1983) Multilingual aplasia examination, 2nd edn. AJA Associate, Iowa City, IA

    Google Scholar 

  17. Zhang X (2016) Quantitative analysis of THC and its metabolites in whole blood using LC-MS/MS for toxicology and forensic laboratories. Waters, the science of what’s possible. www.waters.com/webassets/cms/library/docs/720005769en.pdf

  18. DeCoster MA (2010) Microscopy and image analysis of individual and group cell shape changes during apoptosis microscopy: science, technology, applications and education. Formatex. pp 836–843

  19. Delorme B, Nivet E, Gaillard J, Haupl T, Ringe J, Deveze A, Magnan J, Sohier J et al (2010) The human nose harbors a niche of olfactory ectomesenchymal stem cells displaying neurogenic and osteogenic properties. Stem Cells Dev 19(6):853–866. https://doi.org/10.1089/scd.2009.0267

    Article  CAS  PubMed  Google Scholar 

  20. Borgmann-Winter K, Willard SL, Sinclair D, Mirza N, Turetsky B, Berretta S, Hahn CG (2015) Translational potential of olfactory mucosa for the study of neuropsychiatric illness. Transl Psychiatry 5:e527. https://doi.org/10.1038/tp.2014.141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Benitez-King G, Riquelme A, Ortiz-Lopez L, Berlanga C, Rodriguez-Verdugo MS, Romo F, Calixto E, Solis-Chagoyan H et al (2011) A non-invasive method to isolate the neuronal linage from the nasal epithelium from schizophrenic and bipolar diseases. J Neurosci Methods 201(1):35–45. https://doi.org/10.1016/j.jneumeth.2011.07.009

    Article  CAS  PubMed  Google Scholar 

  22. Benitez-King G, Valdes-Tovar M, Trueta C, Galvan-Arrieta T, Argueta J, Alarcon S, Lora-Castellanos A, Solis-Chagoyan H (2016) The microtubular cytoskeleton of olfactory neurons derived from patients with schizophrenia or with bipolar disorder: implications for biomarker characterization, neuronal physiology and pharmacological screening. Mol Cell Neurosci 73:84–95. https://doi.org/10.1016/j.mcn.2016.01.013

    Article  CAS  PubMed  Google Scholar 

  23. Sacco R, Cacci E, Novarino G (2018) Neural stem cells in neuropsychiatric disorders. Curr Opin Neurobiol 48:131–138. https://doi.org/10.1016/j.conb.2017.12.005

    Article  CAS  PubMed  Google Scholar 

  24. Yamaguchi Y, Miura M (2015) Programmed cell death in neurodevelopment. Dev Cell 32(4):478–490. https://doi.org/10.1016/j.devcel.2015.01.019

    Article  CAS  PubMed  Google Scholar 

  25. Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, Haroutunian V, Fienberg AA (2001) Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci U S A 98(8):4746–4751. https://doi.org/10.1073/pnas.081071198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bowden NA, Scott RJ, Tooney PA (2008) Altered gene expression in the superior temporal gyrus in schizophrenia. BMC Genomics 9:199. https://doi.org/10.1186/1471-2164-9-199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Morin M, Bryan KE, Mayo-Merino F, Goodyear R, Mencia A, Modamio-Hoybjor S, del Castillo I, Cabalka JM et al (2009) In vivo and in vitro effects of two novel gamma-actin (ACTG1) mutations that cause DFNA20/26 hearing impairment. Hum Mol Genet 18(16):3075–3089. https://doi.org/10.1093/hmg/ddp249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Green EK, Grozeva D, Forty L, Gordon-Smith K, Russell E, Farmer A, Hamshere M, Jones IR et al (2013) Association at SYNE1 in both bipolar disorder and recurrent major depression. Mol Psychiatry 18(5):614–617. https://doi.org/10.1038/mp.2012.48

    Article  CAS  PubMed  Google Scholar 

  29. Volk DW, Lewis DA (2016) The role of endocannabinoid signaling in cortical inhibitory neuron dysfunction in schizophrenia. Biol Psychiatry 79(7):595–603. https://doi.org/10.1016/j.biopsych.2015.06.015

    Article  CAS  PubMed  Google Scholar 

  30. Prescot AP, Locatelli AE, Renshaw PF, Yurgelun-Todd DA (2011) Neurochemical alterations in adolescent chronic marijuana smokers: a proton MRS study. Neuroimage 57(1):69–75. https://doi.org/10.1016/j.neuroimage.2011.02.044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Jacobus J, Tapert SF (2014) Effects of cannabis on the adolescent brain. Curr Pharm Des 20(13):2186–2193. https://doi.org/10.2174/13816128113199990426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gubatan J, Staller K, Barshop K, Kuo B (2016) Cannabis abuse is increasing and associated with increased emergency department utilization in gastroenterology patients. Dig Dis Sci 61(7):1844–1852. https://doi.org/10.1007/s10620-016-4090-9

    Article  PubMed  Google Scholar 

  33. Ghasemiesfe M, Barrow B, Leonard S, Keyhani S, Korenstein D (2019) Association between marijuana use and risk of cancer: a systematic review and meta-analysis. JAMA Netw Open 2(11):e1916318. https://doi.org/10.1001/jamanetworkopen.2019.16318

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wolozin B, Sunderland T, Zheng BB, Resau J, Dufy B, Barker J, Swerdlow R, Coon H (1992) Continuous culture of neuronal cells from adult human olfactory epithelium. J Mol Neurosci 3(3):137–146. https://doi.org/10.1007/BF02919405

    Article  CAS  PubMed  Google Scholar 

  35. Hahn CG, Han LY, Rawson NE, Mirza N, Borgmann-Winter K, Lenox RH, Arnold SE (2005) In vivo and in vitro neurogenesis in human olfactory epithelium. J Comp Neurol 483(2):154–163. https://doi.org/10.1002/cne.20424

    Article  PubMed  Google Scholar 

  36. Lin B, Coleman JH, Peterson JN, Zunitch MJ, Jang W, Herrick DB, Schwob JE (2017) Injury induces endogenous reprogramming and dedifferentiation of neuronal progenitors to multipotency. Cell Stem Cell 21(6):761–774 e765. https://doi.org/10.1016/j.stem.2017.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Jimenez-Vaca AL, Benitez-King G, Ruiz V, Ramirez-Rodriguez GB, Hernandez-de la Cruz B, Salamanca-Gomez FA, Gonzalez-Marquez H, Ramirez-Sanchez I et al (2018) Exfoliated human olfactory neuroepithelium: a source of neural progenitor cells. Mol Neurobiol 55(3):2516–2523. https://doi.org/10.1007/s12035-017-0500-z

    Article  CAS  PubMed  Google Scholar 

  38. Jin HJ, Park SK, Oh W, Yang YS, Kim SW, Choi SJ (2009) Down-regulation of CD105 is associated with multi-lineage differentiation in human umbilical cord blood-derived mesenchymal stem cells. Biochem Biophys Res Commun 381(4):676–681. https://doi.org/10.1016/j.bbrc.2009.02.118

    Article  CAS  PubMed  Google Scholar 

  39. Alev C, McIntyre BA, Ota K, Sheng G (2010) Dynamic expression of endoglin, a TGF-beta co-receptor, during pre-circulation vascular development in chick. Int J Dev Biol 54(4):737–742. https://doi.org/10.1387/ijdb.092962ca

    Article  CAS  PubMed  Google Scholar 

  40. Noda S, Kawashima N, Yamamoto M, Hashimoto K, Nara K, Sekiya I, Okiji T (2019) Effect of cell culture density on dental pulp-derived mesenchymal stem cells with reference to osteogenic differentiation. Sci Rep 9(1):5430. https://doi.org/10.1038/s41598-019-41741-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Pedersen SF, Hoffmann EK, Mills JW (2001) The cytoskeleton and cell volume regulation. Comp Biochem Physiol A Mol Integr Physiol 130(3):385–399. https://doi.org/10.1016/s1095-6433(01)00429-9

    Article  CAS  PubMed  Google Scholar 

  42. Fletcher DA, Mullins RD (2010) Cell mechanics and the cytoskeleton. Nature 463(7280):485–492. https://doi.org/10.1038/nature08908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kapitein LC, Hoogenraad CC (2015) Building the neuronal microtubule cytoskeleton. Neuron 87(3):492–506. https://doi.org/10.1016/j.neuron.2015.05.046

    Article  CAS  Google Scholar 

  44. Tahir SK, Zimmerman AM (1991) Influence of marijuana on cellular structures and biochemical activities. Pharmacol Biochem Behav 40(3):617–623. https://doi.org/10.1016/0091-3057(91)90372-9

    Article  CAS  PubMed  Google Scholar 

  45. Fan Y, Abrahamsen G, Mills R, Calderon CC, Tee JY, Leyton L, Murrell W, Cooper-White J et al (2013) Focal adhesion dynamics are altered in schizophrenia. Biol Psychiatry 74(6):418–426. https://doi.org/10.1016/j.biopsych.2013.01.020

    Article  PubMed  Google Scholar 

  46. Tee JY, Sutharsan R, Fan Y, Mackay-Sim A (2017) Cell migration in schizophrenia: patient-derived cells do not regulate motility in response to extracellular matrix. Mol Cell Neurosci 80:111–122. https://doi.org/10.1016/j.mcn.2017.03.005

    Article  CAS  PubMed  Google Scholar 

  47. Tortoriello G, Morris CV, Alpar A, Fuzik J, Shirran SL, Calvigioni D, Keimpema E, Botting CH et al (2014) Miswiring the brain: Delta9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. EMBO J 33(7):668–685. https://doi.org/10.1002/embj.201386035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Newman SD, Cheng H, Schnakenberg Martin A, Dydak U, Dharmadhikari S, Hetrick W, O'Donnell B (2019) An investigation of neurochemical changes in chronic cannabis users. Front Hum Neurosci 13:318. https://doi.org/10.3389/fnhum.2019.00318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kim SH, Yang JW, Kim KH, Kim JU, Yook TH (2019) A review on studies of marijuana for Alzheimer’s disease - focusing on CBD, THC. Aust J Pharm 22(4):225–230. https://doi.org/10.3831/KPI.2019.22.030

    Article  Google Scholar 

  50. Lindsay EA, Vitelli F, Su H, Morishima M, Huynh T, Pramparo T, Jurecic V, Ogunrinu G et al (2001) Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 410(6824):97–101. https://doi.org/10.1038/35065105

    Article  CAS  PubMed  Google Scholar 

  51. Jonas RK, Montojo CA, Bearden CE (2014) The 22q11.2 deletion syndrome as a window into complex neuropsychiatric disorders over the lifespan. Biol Psychiatry 75(5):351–360. https://doi.org/10.1016/j.biopsych.2013.07.019

    Article  CAS  PubMed  Google Scholar 

  52. Ping LY, Chuang YA, Hsu SH, Tsai HY, Cheng MC (2016) Screening for mutations in the TBX1 gene on chromosome 22q11.2 in schizophrenia. Genes (Basel) 7(11). https://doi.org/10.3390/genes7110102

  53. Hiramoto T, Kang G, Suzuki G, Satoh Y, Kucherlapati R, Watanabe Y, Hiroi N (2011) Tbx1: Identification of a 22q11.2 gene as a risk factor for autism spectrum disorder in a mouse model. Hum Mol Genet 20(24):4775–4785. https://doi.org/10.1093/hmg/ddr404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Takahashi T, Okabe S, Broin PO, Nishi A, Ye K, Beckert MV, Izumi T, Machida A et al (2016) Structure and function of neonatal social communication in a genetic mouse model of autism. Mol Psychiatry 21(9):1208–1214. https://doi.org/10.1038/mp.2015.190

    Article  CAS  PubMed  Google Scholar 

  55. Paylor R, Glaser B, Mupo A, Ataliotis P, Spencer C, Sobotka A, Sparks C, Choi CH et al (2006) Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proc Natl Acad Sci U S A 103(20):7729–7734. https://doi.org/10.1073/pnas.0600206103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Katona I (2015) Cannabis and endocannabinoid signaling in epilepsy. Handb Exp Pharmacol 231:285–316. https://doi.org/10.1007/978-3-319-20825-1_10

    Article  CAS  PubMed  Google Scholar 

  57. Brockmann K (2009) The expanding phenotype of GLUT1-deficiency syndrome. Brain and Development 31(7):545–552. https://doi.org/10.1016/j.braindev.2009.02.008

    Article  PubMed  Google Scholar 

  58. Alazami AM, Alzahrani F, Bohlega S, Alkuraya FS (2014) SET binding factor 1 (SBF1) mutation causes Charcot-Marie-tooth disease type 4B3. Neurology 82(18):1665–1666. https://doi.org/10.1212/WNL.0000000000000331

    Article  PubMed  Google Scholar 

  59. Gros-Louis F, Dupre N, Dion P, Fox MA, Laurent S, Verreault S, Sanes JR, Bouchard JP et al (2007) Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia. Nat Genet 39(1):80–85. https://doi.org/10.1038/ng1927

    Article  CAS  PubMed  Google Scholar 

  60. Shalev SA, Tenenbaum-Rakover Y, Horovitz Y, Paz VP, Ye H, Carmody D, Highland HM, Boerwinkle E et al (2014) Microcephaly, epilepsy, and neonatal diabetes due to compound heterozygous mutations in IER3IP1: insights into the natural history of a rare disorder. Pediatr Diabetes 15(3):252–256. https://doi.org/10.1111/pedi.12086

    Article  CAS  PubMed  Google Scholar 

  61. Weber YG, Lerche H (2009) Genetics of paroxysmal dyskinesias. Curr Neurol Neurosci Rep 9(3):206–211. https://doi.org/10.1007/s11910-009-0031-8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr. Antonia Díaz Gañete for her excellent assistance at the beginning of this project, the CIC-Biogune Proteomics platform, especially Dr. Ibon Iloro and Dr. Felix Elortza for their technical assistance. Network images were obtained with IPA, thanks to the assistance provided by the PAB (Andalusian Bioinformatics Platform) center, University of Malaga. We would like to acknowledge the Clinical Research Unit at the IMIM-Hospital del Mar Research Institute for their expertise in nasal brushing, especially to Marta Pérez Otero and Dr. Ana M. Aldea Perona, and to Dr. Aida Cuenca-Royo for the neuropsychological evaluation.

Funding

This study was supported by grants co-financed by the “Fondo Europeo de Desarrollo Regional” (FEDER)-UE “A way to build Europe” from the “Programa Operativo de Andalucía FEDER, Iniciativa Territorial Integrada ITI 2014-2020 Consejería Salud, Junta de Andalucía” (PI-0009-2017); the “Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía” (CTS-510); Plan Nacional sobre Drogas (2019I041), the “Ministerio de Economía, Industria y Competitividad (“Juan de la Cierva Incorporación” postdoctoral grant IJCI-2015-23280), the “Centro de Investigación Biomédica en Red de Salud Mental-CIBERSAM” (CB/07/09/0033; CB/07/09/0029) and Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación de España y fondos FEDER (PI18/00053 to P.R.).

Author information

Author notes

  1. Alejandra Delgado-Sequera and María Hidalgo-Figueroa contributed equally to this work.

Authors and Affiliations

  1. Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Campus Universitario Río San Pedro s/n, 11510, Puerto Real, Cadiz, Spain

    Alejandra Delgado-Sequera, María Hidalgo-Figueroa & Esther Berrocoso

  2. Instituto de Investigación e Innovación Biomédica de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, Spain

    Alejandra Delgado-Sequera, María Hidalgo-Figueroa, Mª Carmen Duran-Ruiz, Carmen Castro, Ismael Sánchez-Gomar, Noelia Geribaldi-Doldán & Esther Berrocoso

  3. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain

    María Hidalgo-Figueroa, Víctor Pérez & Esther Berrocoso

  4. Integrative Pharmacology and Systems Neuroscience, Neurosciences Research Programme, IMIM-Hospital del Mar Research Institute, PRBB, Calle Dr. Aiguader 88, 08003, Barcelona, Spain

    Marta Barrera-Conde, Rafael de la Torre & Patricia Robledo

  5. Department of Experimental and Health Sciences, University Pompeu Fabra, Barcelona, Spain

    Marta Barrera-Conde, Cristina Fernández-Avilés & Patricia Robledo

  6. Biomedicine, Biotechnology and Public Health Department, University of Cádiz, Cádiz, Spain

    Mª Carmen Duran-Ruiz, Carmen Castro, Rafael de la Torre & Ismael Sánchez-Gomar

  7. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain

    Rafael de la Torre

  8. Neuropsychiatry and Addictions Institute (INAD) of Parc de Salut Mar, Barcelona, Spain

    Víctor Pérez

  9. Department of Human Anatomy and Embriology, University of Cádiz, Cádiz, Spain

    Noelia Geribaldi-Doldán

Authors
  1. Alejandra Delgado-Sequera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. María Hidalgo-Figueroa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marta Barrera-Conde
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mª Carmen Duran-Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carmen Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cristina Fernández-Avilés
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rafael de la Torre
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ismael Sánchez-Gomar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Víctor Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Noelia Geribaldi-Doldán
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Patricia Robledo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Esther Berrocoso
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ADS and MHF performed the experiments, collected and analysed the data and prepared the original draft of the manuscript; MCDR and ISG collaborated on the proteomics studies and the studies of apoptosis; CC and NGD collaborated with the cell cultures and immunocytochemical studies; CFA and MBC initially processed the samples and handled the primary cell cultures. PR and RT participated in planning the experiment, and provided financial support. ACR performed the neuropsychological evaluation; EB designed and supervised the research study and wrote the manuscript. All the authors reviewed and approved the final version of the manuscript submitted.

Corresponding authors

Correspondence to Patricia Robledo or Esther Berrocoso.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest

Ethics Approval

The study was reviewed and approved by the local institutional ethics committee (CEIC-PSMAR). All subjects provided their written informed consent after the study and procedures were explained to them in full.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 236 kb)

ESM 2

(DOCX 23 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Delgado-Sequera, A., Hidalgo-Figueroa, M., Barrera-Conde, M. et al. Olfactory Neuroepithelium Cells from Cannabis Users Display Alterations to the Cytoskeleton and to Markers of Adhesion, Proliferation and Apoptosis. Mol Neurobiol 58, 1695–1710 (2021). https://doi.org/10.1007/s12035-020-02205-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-020-02205-9

Keywords

Search

Navigation