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Int J Mol Sci. 2016 Dec 23;18(1). pii: E26. doi: 10.3390/ijms18010026.

Cannabidiol Modulates the Expression of Alzheimer's Disease-Related Genes in Mesenchymal Stem Cells.

Author information

1
IRCCS Centro Neurolesi "Bonino-Pulejo", via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy. rosalianalibro@hotmail.it.
2
Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Chieti-Pescara, via dei Vestini, 31, 66100 Chieti, Italy. francesca.diomede@unich.it.
3
IRCCS Centro Neurolesi "Bonino-Pulejo", via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy. domenico.scionti@gmail.com.
4
Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Chieti-Pescara, via dei Vestini, 31, 66100 Chieti, Italy. adriano.piattelli@unich.it.
5
Council for Research and Experimentation in Agriculture-Research Centre for Industrial Crops (CREA-CIN), 45100 Rovigo, Italy. giampaolo.grassi@gmail.com.
6
Dipartimento di Scienze del Farmaco, Universita del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy. federica.pollastro@uniupo.it.
7
IRCCS Centro Neurolesi "Bonino-Pulejo", via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy. bramanti.dino@gmail.com.
8
IRCCS Centro Neurolesi "Bonino-Pulejo", via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy. emazzon.irccs@gmail.com.
9
Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Chieti-Pescara, via dei Vestini, 31, 66100 Chieti, Italy. trubiani@unich.it.

Abstract

Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of several neurodegenerative disorders, including Alzheimer's disease (AD). The main neuropathological hallmarks of AD are senile plaques, composed of amyloid beta (Aβ), and neurofibrillary tangles, formed by hyperphosphorylated tau. However, current therapies for AD have shown limited efficacy. In this study, we evaluated whether pre-treatment with cannabidiol (CBD), at 5 μM concentration, modulated the transcriptional profile of MSCs derived from gingiva (GMSCs) in order to improve their therapeutic potential, by performing a transcriptomic analysis by the next-generation sequencing (NGS) platform. By comparing the expression profiles between GMSCs treated with CBD (CBD-GMSCs) and control GMSCs (CTR-GMSCs), we found that CBD led to the downregulation of genes linked to AD, including genes coding for the kinases responsible of tau phosphorylation and for the secretases involved in Aβ generation. In parallel, immunocytochemistry analysis has shown that CBD inhibited the expression of GSK3β, a central player in AD pathogenesis, by promoting PI3K/Akt signalling. In order to understand through which receptor CBD exerted these effects, we have performed pre-treatments with receptor antagonists for the cannabinoid receptors (SR141716A and AM630) or for the vanilloid receptor 1 (TRPVI). Here, we have proved that TRPV1 was able to mediate the modulatory effect of CBD on the PI3K/Akt/GSK3β axis. In conclusion, we have found that pre-treatment with CBD prevented the expression of proteins potentially involved in tau phosphorylation and Aβ production in GMSCs. Therefore, we suggested that GMSCs preconditioned with CBD possess a molecular profile that might be more beneficial for the treatment of AD.

KEYWORDS:

Alzheimer’s disease; amyloid beta; cannabidiol; glycogen synthase kinase 3β; mesenchymal stem cells; tau

PMID:
28025562
PMCID:
PMC5297661
DOI:
10.3390/ijms18010026
[Indexed for MEDLINE]
Free PMC Article

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