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  • Noradrenergic stimulation of BDNF synthesis in astrocytes : mediation via [alpha][sup]1- and ß[sup]1/ß[sup]2-adrenergic receptors
    Jurič, Damijana Mojca ; Lončar, Darja ; Čarman-Kržan, Marija
    Brain-derived neurotrophic factor (BDNF) synthesis in astrocytes induced by noradrenaline (NA) is a receptor-mediated process utilizing two parallel adrenergic pathways: ... beta(1)/beta(2)-adrenergic/cAMP and the novel alpha(1)-adrenergic/PKC pathway. BDNF is produced by astrocytes, in addition to neurons, and the noradrenergic system plays a role in controlling BDNF synthesis. Since astrocytes express various subtypes of alpha- and beta-adrenergic receptors that have the potential to be activated by synaptically released NA, we focused our present study on the mediatory role of adrenergic receptors in the noradrenergic up-regulation of BDNF synthesis in cultured neonatal rat cortical astrocytes. NA (1muM) elevates BDNF levels by four-fold after 6h of incubation. Its stimulation was partly inhibited by either the beta(1)-adrenergic antagonist atenolol, the beta(2)-adrenergic antagonist ICI 118,551, or by the alpha(1)-adrenergic antagonist prazosin, while the alpha(2)-adrenergic antagonist yohimbine showed no effect. BDNF levels in astrocytes were increased by the specific beta(1)-adrenergic agonistdobutamine and the beta(2)-adrenergic agonist salbutamol, as well as byadenylate cyclase activation (by forskolin) and PKA activation (by dBcAMP). However, none of the tested agonists or mediators of the intracellular beta-adrenergic pathways were able to reach the level of NA's stimulatoryeffect. BDNF cellular levels were also elevated by the alpha(1)-adrenergic agonist methoxamine, but not by the alpha(2)-adrenergic agonist clonidine. The increase in intracellular Ca(2+) by ionophore A23187 showed no effect, whereas PKC activation by phorbol 12-myristate 13-acetate (TPA) potently stimulated BDNF levels in the cells. (Abstract truncated at 2000 characters)
    Source: Neurochemistry International. - ISSN 0197-0186 (Letn. 52, 2008, str. 297-306)
    Type of material - article, component part
    Publish date - 2008
    Language - english
    COBISS.SI-ID - 23055577

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