Cannabinerol (CBNR) influences synaptic genes associated to cytoskeleton and ion channels in NSC-34 cell line: a transcriptomic study.

Cannabinoids are receiving big attention as a novel approach in the treatment of cognitive and motor disabilities, which characterize neurological disorders. To date, over 100 phytocannabinoids are extracted from Cannabis sativa, and some of them have been shown to display neuroprotective properties and influence synaptic transmission, all this, without psychotropic effects. In this study, we investigated a less known phytocannabinoid, the cannabinerol (CBNR). Using NSC-34 motor neuron-like cell line and the Next-Generation Sequencing analysis, we evaluated the impact of CBNR on neurodevelopment and its effects on synapse-related genes. CBNR resulted to regulate genes involved in nervous system development pathway and the most of them were related to synapses. We reported that CBNR influences synaptic genes associated to synapse organization and specialization, including cytoskeleton and ion channels. Specifically, the calcium, sodium, and potassium channels subunits (Cacna1b, Cacna1c, Cacnb1, Grin1, Scn8a, Kcnc1, Kcnj9, Cabp1?) were upregulated, as well as genes related to NMDAR signaling (Agap3, Syngap1). Moreover, cytoskeletal and cytoskeletal-associated genes (Actn2, Ina, Trio, Marcks, Bsn, Rtn4, Dgkz, Htt) were also regulated by CBNR. These findings suggest the important role exerted by CBNR in the regulation of synaptogenesis and synaptic transmission. A relevant aspect to consider the CBNR an useful drug in the treatment of neurological disorders.