Dados do Trabalho

Título

Cannabidiol induces changes in genes associated with energy metabolism, protein translation, neuroplasticity, and chromatin changes in mice ventral CA1 neurons

Introdução

Cannabidiol (CBD) is one of the most common cannabinoids found in Cannabis sativa flowers. CBD interacts indirectly with cannabinoid receptors and affects several non-cannabinoid targets. CBD has already been investigated as a therapeutic strategy showing anticonvulsant, neuroprotective, and antiepileptic benefits demonstrated in both animal and human models.

Objetivo

To investigate the influence of CBD on the transcriptome we used RNAseq to assess gene expression of the ventral CA1 (vCA1) hippocampus area following intraperitoneal (i.p) administration of CBD for 1 or 7 days compared to controls

Método

Adult C57BL/6JUnib mice (Animal Use Ethics Committee protocol 5367-1/2019) were divided into four groups: CR1 - 1 day administration of NaCl 0,15 M, i.p., CBD1 - 1 day treatment with CBD (100 mg/kg, i.p.), CR7 - 7 days administration of NaCl 0,15 M, i.p., and CBD7 - 7 days treatment with CBD (100 mg/kg, i.p.). CBD (99.6% pure, no other cannabinoid, BSPG-Pharm, Sandwich, UK) was freshly prepared and used. Animals were euthanized 24 hours after the last injection, and their brains were processed for laser microdissection with a Zeiss PALM LCM. Total RNA was isolated from each sample's ventral CA1 pyramidal layer, and libraries were produced for RNA-seq on the Illumina Hiseq platform. The STAR Aligner/DESeq2 pipeline was used to align, quantify, and compare sequences. The clusterProfiler R-package was used to examine GO terms.

Resultados

We obtained the following differentially expressed genes results (adjusted p<0,05): 299 (CBD1xCR1) and 1936 (CBD7xCR7). While PCA for CBD1xCR1 samples overlap, PCA for CBD7xCR7 samples shows an evident clustering. CBD7xCR7’s GO analysis evidenced 76 terms significantly enriched (p.adjust <0.05). Downregulated genes list provided top enriched terms like: 'mitochondrion organization', 'cytoplasmic translation', ‘oxidative phosphorylation’ and 'ribosome biogenesis'. Furthermore, GO analysis for upregulated genes in CBD7xCR7 shows the following most enriched biological terms: ‘covalent chromatin modification’, ‘regulation of cell morphogenesis involved in differentiation’, and ‘synapse organization’.

Conclusão

The present dataset contributes to a deeper understanding of the CBD effects on gene expression in vCA1 of healthy mice and provides evidence that CBD induces an extensive change in neuroplasticity and chromatin regulation genes. Furthermore, CBD induces a marked reduction of protein translation machinery and energy metabolism genes in vCA1 neurons.

Palavras-chave

CBD
Hippocampus