Cannabinerol and NSC-34 Transcriptomic Analysis: Is the Dose Who Makes Neuronal Differentiation?

Abstract

Cannabis sativa L. proved to be a source of several phytocompounds able to help patients facing different diseases. Moreover, these phytocompounds can help ameliorate general conditions and control certain unpleasant effects of diseases. Some cannabinoids, however, provided more benefits applicable to settings other than palliative care. Using the NSC-34 cell line, we evaluated the barely known phytocompound named cannabinerol (CBNR) at different doses, in order to understand its unique characteristics and the ones shared with other cannabinoids. The transcriptomic analysis suggests a possible ongoing neuronal differentiation, principally due to the activation of cannabinoid receptor 1 (CB1), to which the phosphorylation of serine–threonine protein kinase (Akt) followed, especially between 20 and 7.5 µM. The increase of Neurod1 and Map2 genes at 7.5 µM, accompanied by a decrease of Vim, as well as the increase of Syp at all the other doses, point toward the initiation of differentiation signals. Our preliminary results indicate CBNR as a promising candidate to be added to the list of cannabinoids with neuronal differentiation-enhancer properties. However, further studies are needed to confirm this initial insight.

Cannabinerol (CBNR) Influences Synaptic Genes Associated with Cytoskeleton and Ion Channels in NSC-34 Cell Line: A Transcriptomic Study

“…Recently, minor cannabinoids, such as ∆ 8 -THC and CBNR, have also been studied to elucidate whether they exhibit similar neuroprotective properties compared to major ones [13,14]. In this regard, ∆ 8 -THC protected retinoic acid-differentiated neuroblastoma SH-SY5Y cells against amyloid beta (Aβ) toxicity.…”

“…In this study, we focused our attention on CBNR, a geometric isomer of CBG, that we have previously tested for its involvement in neuronal differentiation [14]. Here, we investigated the impact of CBNR on the physiology of NSC-34 motor-neuron-like cells and its effects on the regulation of synaptic-related genes.…”

“…CBNR was dissolved in dimethylsulfoxide (DMSO) (#D8418, Sigma-Aldrich, Saint Louis, MO, USA) and further diluted in phosphate-buffered saline (PBS) 1× (#806552, Sigma-Aldrich, Saint Louis, MO, USA). The final DMSO concentration was <0.1 In a previous study, we have already shown that CBNR is not cytotoxic at the concentration of 10 µM, using the MTT assay [14]. At the end of the treatment, cells were further processed for RNA extraction or immunocytochemistry as reported in the following paragraphs.…”

“…A precise definition of minor phytocannabinoids is missing, but this term is used to indicate those phytocannabinoids different from the "Big Four" whose biological profile is still poorly characterized [12]. Recently, our group has investigated the effects of some minor cannabinoids, such as ∆ 8 -tetrahydrocannabinol (∆ 8 -THC) and the less-known cannabinerol (CBNR), showing their role in neuronal differentiation [13,14]. In differentiated SH-SY5Y cells, ∆ 8 -THC at the concentration of 20 µM resulted in the upregulation of the expression of genes involved in the glutamatergic pathway and the inhibition of the expression of genes in the cholinergic one.…”

Neuroprotection by the cannabis-related products, cannabidiol and cannabigerol, and their associated mechanisms of action

“…In contrast, the evaluation of CBG as a neuroprotective agent is much less reported. Recently, a preclinical study reported that the CBG pre-treatment of the NSC-34 cellular line before the injury, was able to attenuate apoptosis signaling and was proposed as an effective neuroprotective agent (Valeri et al 2022). Another study has shown that CBG pre-treatment reduces the loss of cell viability induced by the medium of LPS-stimulated macrophages in NSC-34 cells (Gugliandolo et al 2018).…”