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Título: | Neuroplasticity pathways -ß-catenin, AKT/PKB, BDNF- in an animal model of depression: influence of chronic F9-tetrahydrocannabinol administration |
Autor: | Pilar-Cuéllar, Fuencisla CSIC ORCID; Madureira, Rebeca CSIC; Díaz, Álvaro CSIC ORCID; Pazos, Ángel CSIC ORCID; Valdizán, Elsa M. CSIC ORCID | Fecha de publicación: | 2009 | Citación: | 10ª SEIC (2009) | Resumen: | The endogenous cannabinoid system is involved in the pathophysiology of depression: an increase of CB1 receptor density and functionality is present in animal models of depression, such as olfactory bulbectomy; and increased endocannabinoid levels have been reported in frontal cortex of suicide victims. On the other hand, several intracellular pathways involved in cell proliferation and fate of adult hippocampal stem/progenitor cells (AHPs), including ß-catenin, AKT/PKB and BDNF, are modulated by antidepressants: fluoxetine (SSRI) treatment has been reported to induce an increase in AKT/PKB pathway activity, cytosolic ß-catenin levels and BDNF expression. Here we study the modulation of the effects of fluoxetine treatment on these intracellular pathways in hippocampus by the coadministration of the cannabinoid agonist [delta]9-tetrahydrocannabinol (THC). We measured ß-catenin, AKT and BDNF protein levels by Western blot in male Sprague Dawley rats following the chronic administration of THC (10 mg/kg/day, 21 days; i.p.), fluoxetine (10 mg/kg/day, 21 days; p.o.), or the combination of both THC+fluoxetine. In OB+vehicle group a clear but not significant reduction of ß-catenin, AKT and BDNF protein levels vs sham+vehicle. THC and fluoxetine treatments produced an increase of ß-catenin, AKT and BDNF protein levels in hippocampal homogenates (p<0,05). A significantly higher effect was observed in the group corresponding to the association THC+fluoxetine (p<0,01) for these three markers. Thus we conclude that 1) in the olfactory bulbectomy model of depression there is a tendency to the reduction of a series of proliferative pathways in the hippocampus, such as ß-catenin, AKT/PKB and BDNF; and 2) both fluoxetine and THC treatments reverse these depression-associated neuroplastic changes, suggesting the implication of the cannabinoid system in the therapeutic antidepressant response. | Descripción: | Trabajo presentado a la 10ª Reunión anual de la Sociedad Española de Investigación sobre Cannabinoides celebrada en Santander del 26 al 28 de noviembre de 2009. | URI: | http://hdl.handle.net/10261/79540 |
Aparece en las colecciones: | (IBBTEC) Comunicaciones congresos |
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