Analysis of endocannabinoid signaling elements and related proteins in lymphocytes of patients with Dravet syndrome.

Autor: Rubio M; Departamento de Bioquímica y Biología Molecular Facultad de Medicina Instituto Universitario de Investigación en Neuroquímica Universidad Complutense Madrid Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Madrid Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) Madrid Spain., Valdeolivas S; Departamento de Bioquímica y Biología Molecular Facultad de Medicina Instituto Universitario de Investigación en Neuroquímica Universidad Complutense Madrid Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Madrid Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) Madrid Spain., Piscitelli F; Endocannabinoid Research Group Institute of Biomolecular Chemistry Consiglio Nazionale delle Ricerche Pozzuoli, Naples Italy., Verde R; Endocannabinoid Research Group Institute of Biomolecular Chemistry Consiglio Nazionale delle Ricerche Pozzuoli, Naples Italy., Satta V; Departamento de Bioquímica y Biología Molecular Facultad de Medicina Instituto Universitario de Investigación en Neuroquímica Universidad Complutense Madrid Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Madrid Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) Madrid Spain., Barroso E; Instituto de Genética Médica y Molecular (INGEMM)Hospital Universitario La Paz Universidad Autónoma de MadridIdi PAZ Madrid Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Raras (CIBERER) Instituto de Salud Carlos III Madrid Spain., Montolio M; Dravet Syndrome Foundation Madrid Spain; Departamento de Biología Celular Facultad de Biología Universidad de Barcelona Barcelona Spain., Aras LM; Dravet Syndrome Foundation Madrid Spain; Servicio Navarro de Salud Osasunbidea Estella Spain., Di Marzo V; Endocannabinoid Research Group Institute of Biomolecular Chemistry Consiglio Nazionale delle Ricerche Pozzuoli, Naples Italy., Sagredo O; Departamento de Bioquímica y Biología Molecular Facultad de Medicina Instituto Universitario de Investigación en Neuroquímica Universidad Complutense Madrid Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Madrid Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) Madrid Spain., Fernández-Ruiz J; Departamento de Bioquímica y Biología Molecular Facultad de Medicina Instituto Universitario de Investigación en Neuroquímica Universidad Complutense Madrid Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Madrid Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) Madrid Spain.
Jazyk: angličtina
Zdroj: Pharmacology research & perspectives [Pharmacol Res Perspect] 2016 Mar 05; Vol. 4 (2), pp. e00220. Date of Electronic Publication: 2016 Mar 05 (Print Publication: 2016).
DOI: 10.1002/prp2.220
Abstrakt: Cannabidiol (CBD) reduces seizures in childhood epilepsy syndromes including Dravet syndrome (DS). A formulation of CBD has obtained orphan drug designation for these syndromes and clinical trials are currently underway. The mechanism responsible for CBD effects is not known, although it could involve targets sensitive to CBD in other neurological disorders. We believe of interest to investigate whether these potential targets are altered in DS, in particular whether the endocannabinoid system is dysregulated. To this end, lymphocytes from patients and controls were used for analysis of gene expression of transmitter receptors and transporters, ion channels, and enzymes associated with CBD effects, as well as endocannabinoid genes. Plasma endocannabinoid levels were also analyzed. There were no differences between DS patients and controls in most of the CBD targets analyzed, except an increase in the voltage-dependent calcium channel α-1h subunit. We also found that cannabinoid type-2 (CB 2) receptor gene expression was elevated in DS patients, with no changes in other endocannabinoid-related receptors and enzymes, as well as in plasma levels of endocannabinoids. Such elevation was paralleled by an increase in CD70, a marker of lymphocyte activation, and certain trends in inflammation-related proteins (e.g., peroxisome proliferator-activated receptor-γ receptors, cytokines). In conclusion, together with changes in the voltage-dependent calcium channel α-1h subunit, we found an upregulation of CB 2 receptors, associated with an activation of lymphocytes and changes in inflammation-related genes, in DS patients. Such changes were also reported in inflammatory disorders and may indirectly support the occurrence of a potential dysregulation of the endocannabinoid system in the brain.
Databáze: MEDLINE
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