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