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Titre du document / Document title

Chronic treatment with desipramine and fluoxetine modulate BDNF, CaMKKα and CAMKKβ mRNA levels in the hippocampus of transgenic mice expressing antisense RNA against the glucocorticoid receptor

Auteur(s) / Author(s)

VINET Jonathan ; CARRA Serena ; BLOM Joan M. C. ; BRUNELLO Nicoletta ; BARDEN Nicholas ; TASCEDDA Fabio ;

Résumé / Abstract

Antidepressants up-regulate the cAMP response element binding protein (CREB) and the brain-derived neurotrophic factor (BDNF) in hippocampus and these effects contribute to the protection of hippocampal neurons from stressful stimuli such as high glucocorticoid levels. CREB can be activated by both protein kinase A and by Ca2+-calmodulin-dependent protein kinases (CaMKs), which are in turn phosphorylated by their upstream activators CaMKKa and CaMMKKβ. Using in situ hybridization, we examined the effects of chronic treatment with fluoxetine (FLU) or desipramine (DMI) on BDNF, CaMKKa and CaMKKp mRNAs in the hippocampus of wild-type (Wt) and transgenic (TG) mice characterized by glucocorticoid receptor (GR) dysfunction. Basal levels of CaMKKp were down regulated in the CA3 region of TG mice. DMI decreased the expression of both CaMKKa and CaMMKKβ in the CA3 region of Wt mice. FLU up-regulated BDNF mRNA levels in the CA3 of TG animals while both FLU and DMI increased BDNF gene expression in the dentate gyrus (DG) of TG animals. Our results demonstrate a different regulation of BDNF expression by antidepressant drugs in the hippocampus of Wt and TG animals. Moreover, for the first time, a role for CaMKKs in the mechanism of action of antidepressant agents, at least in the hippocampus, is reported. These data are discussed in view of interactions existing between CaMK pathway and GR-mediated gene transcription.

Revue / Journal Title

Neuropharmacology    ISSN  0028-3908   CODEN NEPHBW 

Source / Source

2004, vol. 47, no7, pp. 1062-1069 [8 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Kidlington, ROYAUME-UNI  (1970) (Revue)

Localisation / Location

INIST-CNRS, Cote INIST : 10408, 35400012539897.0110

Nº notice refdoc (ud4) : 16753801



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