RT Journal Article
SR Electronic
T1 Cells and Molecules Underpinning Cannabis-Related Variations in Cortical Thickness during Adolescence
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP e2256232024
DO 10.1523/JNEUROSCI.2256-23.2024
VO 44
IS 41
A1 Navarri, Xavier
A1 Robertson, Derek N.
A1 Charfi, Iness
A1 Wünnemann, Florian
A1 Sâmia Fernandes do Nascimento, Antônia
A1 Trottier, Giacomo
A1 Leclerc, Sévérine
A1 Andelfinger, Gregor U.
A1 Di Cristo, Graziella
A1 Richer, Louis
A1 Pike, G. Bruce
A1 Pausova, Zdenka
A1 Piñeyro, Graciela
A1 Paus, Tomáš
YR 2024
UL http://www.jneurosci.org/content/44/41/e2256232024.abstract
AB During adolescence, cannabis experimentation is common, and its association with interindividual variations in brain maturation well studied. Cellular and molecular underpinnings of these system-level relationships are, however, unclear. We thus conducted a three-step study. First, we exposed adolescent male mice to Δ-9-tetrahydrocannabinol (THC) or a synthetic cannabinoid WIN 55,212-2 (WIN) and assessed differentially expressed genes (DEGs), spine numbers, and dendritic complexity in their frontal cortex. Second, in human (male) adolescents, we examined group differences in cortical thickness in 34 brain regions, using magnetic resonance imaging, between those who experimented with cannabis before age 16 (n = 140) and those who did not (n = 327). Finally, we correlated spatially these group differences with gene expression of human homologs of mouse-identified DEGs. The spatial expression of 13 THC-related human homologs of DEGs correlated with cannabis-related variations in cortical thickness, and virtual histology revealed coexpression patterns of these 13 genes with cell-specific markers of astrocytes, microglia, and a type of pyramidal cells enriched in dendrite-regulating genes. Similarly, the spatial expression of 18 WIN-related human homologs of DEGs correlated with group differences in cortical thickness and showed coexpression patterns with the same three cell types. Gene ontology analysis indicated that 37 THC-related human homologs are enriched in neuron projection development, while 33 WIN-related homologs are enriched in processes associated with learning and memory. In mice, we observed spine loss and lower dendritic complexity in pyramidal cells of THC-exposed animals (vs controls). Experimentation with cannabis during adolescence may influence cortical thickness by impacting glutamatergic synapses and dendritic arborization.