Time-dependent activation of MAPK/Erk1/2 and Akt/GSK3 cascades: modulation by agomelatine

BMC Neuroscience

Daniela Tardito²  Giorgio Racagni¹  Paolo Tornese²  Mariagrazia Pelizzari²  Giulia Treccani²  Alessandra Mallei²  Mara Seguini²  Laura Musazzi² 

[1] Istituto di Ricovero e Cura a Carattere Scientifico Centro S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy;Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and Center of Excellence on Neurodegenerative Diseases (CEND), Università degli Studi di Milano, Via Balzaretti 9, Milano 20133, Italy

关键词: Time-dependent regulation;    Neuroplasticity;    Intracellular signalling;    Agomelatine;    Antidepressant;   

Others  :  1090796
DOI  :  10.1186/s12868-014-0119-1

 received in 2014-08-08, accepted in 2014-10-09,  发布年份 2014

【 摘 要 】

Background

The novel antidepressant agomelatine, a melatonergic MT₁/MT₂ agonist combined with 5-HT_2c serotonin antagonist properties, showed antidepressant action in preclinical and clinical studies. There is a general agreement that the therapeutic action of antidepressants needs the activation of slow-onset adaptations in downstream signalling pathways finally regulating neuroplasticity. In the last several years, particular attention was given to cAMP-responsive element binding protein (CREB)-related pathways, since it was shown that chronic antidepressants increase CREB phosphorylation and transcriptional activity, through the activation of calcium/calmodulin-dependent (CaM) and mitogen activated protein kinase cascades (MAPK/Erk1/2).

Aim of this work was to analyse possible effects of chronic agomelatine on time-dependent changes of different intracellular signalling pathways in hippocampus and prefrontal/frontal cortex of male rats. To this end, measurements were performed 1 h or 16 h after the last agomelatine or vehicle injection.

Results

We have found that in naïve rats chronic agomelatine, contrary to traditional antidepressants, did not increase CREB phosphorylation, but modulates the time-dependent regulation of MAPK/Erk1/2 and Akt/glycogen synthase kinase-3 (GSK-3) pathways.

Conclusion

Our results suggest that the intracellular molecular mechanisms modulated by chronic agomelatine may be partly different from those of traditional antidepressants and involve the time-dependent regulation of MAPK/Erk1/2 and Akt/GSK-3 signalling pathways. This could exert a role in the antidepressant efficacy of the drug.

【 授权许可】

   
2014 Musazzi et al.; licensee BioMed Central Ltd.

【 图 表 】

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