Signal transduction routes implicated in hippocampal neurogenesis are altered in the olfactory bulbectomized aniaml model of depression

Autor: Díaz, Álvaro, Rodríguez-Gaztelumendi, A., Madureira, Rebeca, Rojo, María Luisa, Pazos, Ángel, Valdizán, Elsa M.
Rok vydání: 2008
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
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Popis: Trabajo presentado al XXX Congreso de la Sociedad Española de Farmacología celebrado en Bilbao del 17 al 19 de septiembre de 2008.
Bilateral olfactory bulbectomy in rat (OB) resembles many neurochemical, pharmacological and structural features observed in human depression that are reversed by chronic antidepressants. Adult hippocampal neurogenesis has been implicated in the pathogenesis of mood disorders and in the molecular mechanisms underlying antidepressant therapeutic effects. In this work, we have aimed to analyse OB-induced time-course changes in the expression of several intracellular elements modulating the ß-catenin pathway and, therefore, implicated in adult brain neurogenesis. OB-induced syndrome in adult male rats was confirmed at 30, 45 and 90 days postsurgery as the typical behavioural hyperactivity in the open-field test. Animals were sacrificed and immunoblotting assays for ß-catenin, AKT, pERK, and TrKB protein expression were perfomed using total cell hippocampal lisates from OB rats and their sham-operated counterparts (control group). The expression of ß-catenin (-30.0 ± 7.2%) and AKT proteins (-29.3 ± 10.3%) were significantly reduced at 45 days postsurgery. However, expression levels were similar to those of control group (100%) after 90 days postsurgery. Interestingly, this recovery was accompanied by an overexpression of TrKB (+36.8 ± 16.2%), and phosphorylated fractions of ERK1 (+80.2 ± 24.9%) and ERK2 (+86.0 ± 15.2%). Our results demonstrate the existence of temporal changes following olfactory bulbectomy in the signalling pathways involved in neuronal proliferative processes. Also, we confirm the utility of this animal model for studying the neurobiology and treatment of depression.
Supported by MEC (SAF 07/61862 and SAF 2005/06087), Mental Health CIBER (ISCIII) and Fundación Alicia Koplowitz and Fundación de Investigación Médica Mutua Madrileña.
Databáze: OpenAIRE
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