Adolescent exposure to Δ9-tetrahydrocannabinol alters the transcriptional trajectory and dendritic architecture of prefrontal pyramidal neurons.
Michael L Miller, Benjamin J. Chadwick, Dara L Dickstein, Immanuel Purushothaman, Gabor Egervari, Tanni Rahman, Chloe Tessereau, Patrick R. Hof, Panos Roussos, Li Shen, Mark G Baxter, Yasmin L. Hurd
Molecular Psychiatry April 2019 DOI: 10.1038/s41380-018-0243-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Adolescent rats |
| Intervention | Δ9-tetrahydrocannabinol (THC) |
| Topics | Cannabis |
| Key points | Adolescent THC exposure in rats disrupted normal prefrontal cortex development by causing premature dendritic spine pruning and atrophy of dendritic arborization in early adulthood, with minimal overlap in developmental transcriptomes between THC- and vehicle-exposed animals. THC altered gene networks related to cell morphogenesis, dendritic development, and cytoskeleton organization, and dysregulated networks shared with schizophrenia patients were enriched for cytoskeletal and neurite development, which the authors suggest could enhance vulnerability to psychiatric disorders. |
Abstract
Neuronal circuits within the prefrontal cortex (PFC) mediate higher cognitive functions and emotional regulation that are disrupted in psychiatric disorders. The PFC undergoes significant maturation during adolescence, a period when cannabis use in humans has been linked to subsequent vulnerability to psychiatric disorders such as addiction and schizophrenia. Here, we investigated in a rat model the effects of adolescent exposure to Δ9-tetrahydrocannabinol (THC), a psychoactive component of cannabis, on the morphological architecture and transcriptional profile of layer III pyramidal neurons-using cell type- and layer-specific high-resolution microscopy, laser capture microdissection and next-generation RNA-sequencing. The results confirmed known normal expansions in basal dendritic arborization and dendritic spine pruning during the transition from late adolescence to early adulthood that were accompanied by differential expression of gene networks associated with neurodevelopment in control animals. In contrast, THC exposure disrupted the normal developmental process by inducing premature pruning of dendritic spines and allostatic atrophy of dendritic arborization in early adulthood. Surprisingly, there was minimal overlap of the developmental transcriptomes between THC- and vehicle-exposed rats. THC altered functional gene networks related to cell morphogenesis, dendritic development, and cytoskeleton organization. Marked developmental network disturbances were evident for epigenetic regulators with enhanced co-expression of chromatin- and dendrite-related genes in THC-treated animals. Dysregulated PFC co-expression networks common to both the THC-treated animals and patients with schizophrenia were enriched for cytoskeletal and neurite development. Overall, adolescent THC exposure altered the morphological and transcriptional trajectory of PFC pyramidal neurons, which could enhance vulnerability to psychiatric disorders.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions Neuropsychopharmacology August 22, 2022
- Neurotoxic or Protective Cannabis Components: Delta-9-Tetrahydrocannabinol ( Δ9 THC) and Cannabidiol (CBD) Journal of Exploratory Research in Pharmacology July 12, 2023
- Prolonged incubation with Δ9-tetrahydrocannabinol but not with cannabidiol induces synaptic alterations and mitochondrial impairment in immature and mature rat organotypic hippocampal slices. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie February 1, 2025
- Adolescent Exposure to a THC-Rich Cannabis Extract Produces Genotype-Dependent Effects on Cognition and Glial Morphology in Serine Racemase Mutant Mice. Journal of Neurochemistry September 2026
- Cannabis, psychosis, and violence: case reports and comprehensive evidence review Frontiers in Psychiatry July 21, 2026
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