Cannabidiol Promotes Neuronal Differentiation Using Akt and Erk Pathways Triggered by Cb1 Signaling

Blando, Santino; Raffaele, Ivana; Chiricosta, Luigi; Valeri, Andrea; Silvestro, Serena; Pollastro, Federica; Mazzon, Emanuela

doi:10.3390/molecules27175644

Cited by 6 publications

(3 citation statements)

References 59 publications

(69 reference statements)

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“…The motor neuron cell line, NSC-34, provided by Cellutions Biosystem Inc., Cedarlane (Burlington, ON, Canada), was maintained in Dulbecco’s modified Eagle’s medium (DMEM) high glucose (#D5671, Sigma-Aldrich, St. Louis, MO, USA) supplemented with 1% L-glutamine (#G7513, Sigma-Aldrich, St. Louis, MO, USA), 1% penicillin/streptomycin (#P0781, Sigma-Aldrich, St. Louis, MO, USA) and 10% FBS (fetal bovine serum, not heat-inactivated) (#F7524, Sigma-Aldrich, St. Louis, MO, USA), at 37 °C in 5% CO 2 /95% air humidified atmosphere. Cells were subcultured every 2–3 days when cell density reached nearly 80–90% [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Cannabinol Regulates the Expression of Cell Cycle-Associated Genes in Motor Neuron-like NSC-34: A Transcriptomic Analysis

Trainito,

Gugliandolo,

Chiricosta

et al. 2024

Biomedicines

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Cannabinoids are reported to have neuroprotective properties and play a role in neurogenesis and neuroplasticity in in vitro and in vivo models. Cannabinol (CBN) is a minor cannabinoid produced by the degradation of Δ9-tetrahydrocannabinol in Cannabis sativa L. and exhibits anti-oxidant, analgesic, anti-bacterial, and anti-inflammatory effects. In this study, we explored the biological effects of 20 µM CBN (6.20 µg/mL) on differentiated NSC-34 cells by MTT assay and next-generation sequencing analysis on the transcriptome. KEGG and Gene Ontology enrichment analyses have been performed to evaluate potential CBN-associated processes. Our results highlighted the absence of any cytotoxic effect of CBN. The comparative transcriptomic analysis pointed out the downregulation of Cdkn2a, Cdkn2c and Cdkn2d genes, which are known to suppress the cell cycle. Ccne2, Cdk2, Cdk7, Anapc11, Anapc10, Cdc23, Cdc16, Anapc4, Cdc27, Stag1, Smc3, Smc1a, Nipbl, Pds5a, Pds5b, and Wapl genes, renowned for their role as cell cycle progression activators, were instead upregulated. Our work suggests that CBN regulates the expression of many genes related to the cell cycle, which are required for axonal maturation, migration, and synaptic plasticity, while not affecting the expression of genes involved in cell death or tumorigenesis.

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Section: Methodsmentioning

confidence: 99%

Cannabinol Regulates the Expression of Cell Cycle-Associated Genes in Motor Neuron-like NSC-34: A Transcriptomic Analysis

Trainito,

Gugliandolo,

Chiricosta

et al. 2024

Biomedicines

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“…CB1Rs promote extracellular signal-regulated kinase 1/2 (ERK1/2) activation [ 45 , 46 , 47 ]. This pathway regulates microglia’s inflammatory gene expression and immune responses and has been linked to neuroinflammation and neurodegenerative diseases [ 48 , 49 ]. For example, in the EAE model, inhibition of ERK activation reduces the severity of the disease.…”

Section: Cannabinoid Receptors and Immunomodulationmentioning

confidence: 99%

Cannabinoids’ Role in Modulating Central and Peripheral Immunity in Neurodegenerative Diseases

Sharon,

Yarmolinsky,

Khalfin

et al. 2024

IJMS

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Cannabinoids (the endocannabinoids, the synthetic cannabinoids, and the phytocannabinoids) are well known for their various pharmacological properties, including neuroprotective and anti-inflammatory features, which are fundamentally important for the treatment of neurodegenerative diseases. The aging of the global population is causing an increase in these diseases that require the development of effective drugs to be even more urgent. Taking into account the unavailability of effective drugs for neurodegenerative diseases, it seems appropriate to consider the role of cannabinoids in the treatment of these diseases. To our knowledge, few reviews are devoted to cannabinoids’ impact on modulating central and peripheral immunity in neurodegenerative diseases. The objective of this review is to provide the best possible information about the cannabinoid receptors and immuno-modulation features, peripheral immune modulation by cannabinoids, cannabinoid-based therapies for the treatment of neurological disorders, and the future development prospects of making cannabinoids versatile tools in the pursuit of effective drugs.

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“…Cannabis sativa L. is a plant belonging to the Cannabaceae family that has been widely used, since ancient times, for both recreational and medical purposes [ 1 ]. C. sativa contains different terpeno-phenolic compounds called cannabinoids [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

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

Valeri

Chiricosta

D’Angiolini

et al. 2023

Life

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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.

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Cannabidiol Promotes Neuronal Differentiation Using Akt and Erk Pathways Triggered by Cb1 Signaling

Cited by 6 publications

References 59 publications

Cannabinol Regulates the Expression of Cell Cycle-Associated Genes in Motor Neuron-like NSC-34: A Transcriptomic Analysis

Cannabinol Regulates the Expression of Cell Cycle-Associated Genes in Motor Neuron-like NSC-34: A Transcriptomic Analysis

Cannabinoids’ Role in Modulating Central and Peripheral Immunity in Neurodegenerative Diseases

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

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