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bioRxiv · 10.1101/2023.07.10.548420

Cannabidiol administration reduces the expression of genes involved in mitochondrial electron transport chain and ribosome biogenesis in mice CA1 neurons

Machado, J. P.·Almeida, V.·Zuardi, A. W.·Hallak, J. E.·Crippa, J. A.·Schwambach Vieira, A.
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Abstract

BackgroundCannabidiol (CBD), one of the main cannabinoids present in the female flowers of Cannabis sativa, has been a therapeutic alternative for a plurality of disorders. Previous investigation has already provided insights into the CBD molecular mechanism, however, there is no transcriptome data for CBD effects on hippocampal subfields. Here, we explore the transcriptomic changes in dorsal and ventral CA1 of adult mice hippocampus after 100 mg/kg of CBD administration (i.p.) for one or seven consecutive days. MethodsC57BL/6JUnib mice were divided into 4 groups treated with either vehicle or CBD for 1 or 7 days. The collected brains were sectioned and the hippocampal subregions were laser microdissected for RNA-Seq analysis. Data alignment, quantification and analysis were conducted with the STAR Aligner/DESeq2/clusterProfiler R-package pipeline. ResultsWe found changes in gene expression in CA1 neurons after single and multiple CBD administrations. Furthermore, the enrichment analysis of differentially expressed genes following 7 days of CBD administration indicates a widespread decrease in the expression levels of electron transport chain and ribosome biogenesis transcripts, while chromatin modifications and synapse organization transcripts were increased. ConclusionThis dataset provides a significant contribution toward advancing our comprehension of the mechanisms responsible for CBD effects on hippocampal neurons. The findings suggest that CBD prompts a significant reduction in energy metabolism genes and the protein translation machinery in CA1 neurons. SIGNIFICANT OUTCOMESWe identified distinct changes in gene expression of CA1 neurons following both single and multiple administrations of CBD. This highlights the molecular impact of CBD on hippocampal neurons and expands our understanding of its mechanisms of action. We revealed that repeated CBD administration led to a greater number of gene expression alterations compared to a single administration, emphasizing the importance of treatment frequency in modulating gene expression. We found that daily CBD administration for seven days resulted in the downregulation of genes related to energy metabolism and protein synthesis/degradation, while genes involved in chromatin regulation and synapse organization were upregulated. These specific gene expression changes shed light on potential cellular effects and molecular mechanisms underlying CBDs actions in the hippocampus. LIMITATIONSOne limitation of this study is its reliance on animal models, specifically C57BL/6JUnib mice, which may not fully reflect human responses to CBD. Additionally, the study primarily investigated the effects of CBD under healthy conditions and did not directly address its therapeutic effects for specific disorders or conditions. Thus, the clinical relevance and applicability of the findings to therapeutic interventions remain to be determined.

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Machado, J. P., Almeida, V., Zuardi, A. W., Hallak, J. E., Crippa, J. A., Schwambach Vieira, A.. 2023-07-11. Cannabidiol administration reduces the expression of genes involved in mitochondrial electron transport chain and ribosome biogenesis in mice CA1 neurons. https://doi.org/10.1101/2023.07.10.548420

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