Cannabichromene Induces Neuronal Differentiation in NSC-34 Cells: Insights from Transcriptomic Analysis

Abstract

Phytocannabinoids, with their variety of beneficial effects, represent a valid group of substances that could be employed as neurogenesis-enhancers or neuronal differentiation inducers. We focused our attention on the neuronal-related potential of cannabichromene (CBC) when administered to undifferentiated NSC-34 for 24 h. Transcriptomic analysis showed an upregulation of several neuronal markers, such as Neurod1 and Tubb3, as well as indicators of neuronal differentiation process progression, such as Pax6. An in-depth investigation of the processes involved in neuronal differentiation indicates positive cytoskeleton remodeling by upregulation of Cfl2 and Tubg1, and active differentiation-targeted transcriptional program, suggested by Phox2b and Hes1. After 48 h of treatment, the markers previously examined in the transcriptomic analysis are still overexpressed, like Ache and Hes1, indicating that the differentiation process is still in progress. The lack of GFAP protein suggests that no astroglial differentiation is taking place, and it is reasonable to indicate the neuronal one as the ongoing one. These results indicate CBC as a potential neuronal differentiation inducer for NSC-34 cells.

The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders

“…However, other cannabinoids have not been extensively studied. Future research could focus on clinical trials to investigate the therapeutic potential of these lesser-known cannabinoids and their derivatives, which have proven in vitro or in vivo biological activity, such as the following: THCV-antiepileptic activity [347], potential against Parkinson's disease [348,349], antipsychotic effects [350], CBG-anticonvulsant activity [351], counteract neuroinflammation [352], neuroprotective in Huntington's disease [202], in multiple sclerosis [353], CBG derivatives-anti-inflammatory in multiple sclerosis [354], in amyotrophic lateral sclerosis [355], neuroprotective potential in Huntington's disease [356], in Parkinson's disease [357][358][359], CBC-promotes neural stem/progenitor cells viability [360], induces neuronal differentiation in NSC-34 Cells [361], antinociceptive activity [362], anti-inflammatory [363], CBN-neuroprotective activity [167], antiseizure potential [364].…”

Co-Dispersion Delivery Systems with Solubilizing Carriers Improving the Solubility and Permeability of Cannabinoids (Cannabidiol, Cannabidiolic Acid, and Cannabichromene) from Cannabis sativa (Henola Variety) Inflorescences

“…CBC positively influenced the viability of adult neural stem progenitor cells during in vitro differentiation, upregulating the marker nestin while downregulating the astrocyte marker Glial fibrillary acidic protein, possibly involving adenosine signaling and ATP modulation in the process [ 35 ]. CBC might be also a potential neuronal differentiation inducer for NSC-34 cells (a hybridoma between spinal cord cells from the embryos of mice and neuroblastoma) [ 36 ]. In addition to the affinity of cannabinoids to selected receptors, there are also non-specific mechanisms of their action within the central nervous system.…”