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Olfactory Neuroepithelium Cells from Cannabis Users Display Alterations to the Cytoskeleton and to Markers of Adhesion, Proliferation and Apoptosis
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  • Alejandra Delgado,
  • Maria Hidalgo,
  • Marta Barrera,
  • Carmen Duran,
  • Carmen Castro,
  • Cristina Fernandez,
  • Rafael de la Torre,
  • Ismael Sanchez,
  • Victor Perez,
  • Noelia Geribladi-Doldán,
  • Patricia Robledo,
  • Esther Berrocoso
Alejandra Delgado
University of Cadiz
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Maria Hidalgo
University of Cadiz
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Marta Barrera
IMIM-Hospital del Mar Research Institute
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Carmen Duran
University of Cadiz
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Carmen Castro
Universidad de Cadiz
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Cristina Fernandez
Pompeu Fabra University
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Rafael de la Torre
Hospital del Mar Institute for Medical Research
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Ismael Sanchez
University of Cadiz
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Victor Perez
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III
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Noelia Geribladi-Doldán
Universidad de Cadiz
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Patricia Robledo
IMIM-Hospital del Mar Research Institute
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Esther Berrocoso
University of Cadiz
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Abstract

Background and Purpose: 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) 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. Experimental Approach: 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. Key Results: 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. Conclusion and Implications: 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.