title: The neuroprotection of cannabidiol against MPP⁺-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson's disease.
abstract: Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa with potential to treat neurodegenerative diseases. Its neuroprotection has been mainly associated with anti-inflammatory and antioxidant events; however, other mechanisms might be involved. We investigated the involvement of neuritogenesis, NGF receptors (trkA), NGF, and neuronal proteins in the mechanism of neuroprotection of CBD against MPP(+) toxicity in PC12 cells. CBD increased cell viability, differentiation, and the expression of axonal (GAP-43) and synaptic (synaptophysin and synapsin I) proteins. Its neuritogenic effect was not dependent or additive to NGF, but it was inhibited by K252a (trkA inhibitor). CBD did not increase the expression of NGF, but protected against its decrease induced by MPP(+), probably by an indirect mechanism. We also evaluated the neuritogenesis in SH-SY5Y cells, which do not express trkA receptors. CBD did not induce neuritogenesis in this cellular model, which supports the involvement of trkA receptors. This is the first study to report the involvement of neuronal proteins and trkA in the neuroprotection of CBD. Our findings suggest that CBD has a neurorestorative potential independent of NGF that might contribute to its neuroprotection against MPP(+), a neurotoxin relevant to Parkinson's disease.
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: neife@fcfrp.usp.br.
authors.forename: Neife Aparecida Guinaim
authors.initials: NA
authors.lastname: Santos
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Nádia Maria
authors.initials: NM
authors.lastname: Martins
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Flávia Malvestio
authors.initials: FM
authors.lastname: Sisti
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Laís Silva
authors.initials: LS
authors.lastname: Fernandes
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Rafaela Scalco
authors.initials: RS
authors.lastname: Ferreira
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Regina Helena Costa
authors.initials: RH
authors.lastname: Queiroz
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Antônio Cardozo
authors.initials: AC
authors.lastname: Santos
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D001369:Axons / Q000378:metabolism; D002185:Cannabidiol / Q000494:pharmacology*; D006801:Humans; D020932:Nerve Growth Factor / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000517:prevention & control*; D051381:Rats; D020917:Receptor, trkA / Q000502:physiology*; D013569:Synapses / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D002185:Cannabidiol; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D015655:1-Methyl-4-phenylpyridinium
keywords: Cannabidiol (CBD); GAP-43; Neuroprotection; Synapsin I; Synaptophysin; trkA receptors