Olfactory Neuroepithelium Cells from Cannabis Users Display Alterations to the Cytoskeleton and to Markers of Adhesion,
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Olfactory Neuroepithelium Cells from Cannabis Users Display Alterations to the Cytoskeleton and to Markers of Adhesion, Proliferation and Apoptosis Alejandra Delgado-Sequera 1,2 & María Hidalgo-Figueroa 1,2,3 & Marta Barrera-Conde 4,5 & Mª Carmen Duran-Ruiz 2,6 & Carmen Castro 2,6 & Cristina Fernández-Avilés 5 & Rafael de la Torre 4,6,7 & Ismael Sánchez-Gomar 2,6 & Víctor Pérez 3,8 & Noelia Geribaldi-Doldán 2,9 & Patricia Robledo 4,5 & Esther Berrocoso 1,2,3 Received: 10 September 2020 / Accepted: 9 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Cannabis . Human olfactory Neuroepithelium . Proteomic . Cytoskeleton . Adhesion . Apoptosis
Alejandra Delgado-Sequera and María Hidalgo-Figueroa contributed equally to this work. * Patricia Robledo [email protected] * Esther Berrocoso [email protected] 1
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Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Campus Universitario Río San Pedro s/n, 11510 Puerto Real, Cadiz, Spain Instituto de Investigación e Innovación Biomédica de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
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Integrative Pharmacology and Systems Neuroscience, Neurosciences Research Pro
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