PMID- 17681645 OWN - NLM STAT- MEDLINE DCOM- 20080505 LR - 20071217 IS - 0197-0186 (Print) IS - 0197-0186 (Linking) VI - 52 IP - 1-2 DP - 2008 Jan TI - Noradrenergic stimulation of BDNF synthesis in astrocytes: mediation via alpha1- and beta1/beta2-adrenergic receptors. PG - 297-306 AB - Brain-derived neurotrophic factor (BDNF) synthesis in astrocytes induced by noradrenaline (NA) is a receptor-mediated process utilizing two parallel adrenergic pathways: beta1/beta2-adrenergic/cAMP and the novel alpha1-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 (1 microM) elevates BDNF levels by four-fold after 6 h of incubation. Its stimulation was partly inhibited by either the beta1-adrenergic antagonist atenolol, the beta2-adrenergic antagonist ICI 118,551, or by the alpha1-adrenergic antagonist prazosin, while the alpha2-adrenergic antagonist yohimbine showed no effect. BDNF levels in astrocytes were increased by the specific beta1-adrenergic agonist dobutamine and the beta2-adrenergic agonist salbutamol, as well as by adenylate 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 stimulatory effect. BDNF cellular levels were also elevated by the alpha1-adrenergic agonist methoxamine, but not by the alpha2-adrenergic agonist clonidine. The increase in intracellular Ca2+ by ionophore A23187 showed no effect, whereas PKC activation by phorbol 12-myristate 13-acetate (TPA) potently stimulated BDNF levels in the cells. The methoxamine-stimulated BDNF synthesis was inhibited by desensitizing pretreatment with TPA, indicating that the alpha1-stimulation was mediated via PKC activation. In conclusion, the synthesis of astrocytic BDNF stimulated by noradrenergic neuronal activity is an adaptable process using multiple types (alpha1 and beta1/beta2) of adrenergic receptor activation. FAU - Juric, Damijana Mojca AU - Juric DM AD - Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, Ljubljana SI-1000, Slovenia. damijana-mojca.juric@mf.uni-lj.si FAU - Loncar, Darja AU - Loncar D FAU - Carman-Krzan, Marija AU - Carman-Krzan M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070704 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Adrenergic Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, Adrenergic) SB - IM MH - Adrenergic Agents/pharmacology MH - Animals MH - Astrocytes/*metabolism MH - Brain-Derived Neurotrophic Factor/*biosynthesis MH - Cells, Cultured MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Pregnancy MH - Rats MH - Rats, Wistar MH - Receptors, Adrenergic/*physiology EDAT- 2007/08/08 09:00 MHDA- 2008/05/06 09:00 CRDT- 2007/08/08 09:00 PHST- 2007/05/05 00:00 [received] PHST- 2007/06/23 00:00 [revised] PHST- 2007/06/28 00:00 [accepted] PHST- 2007/08/08 09:00 [pubmed] PHST- 2008/05/06 09:00 [medline] PHST- 2007/08/08 09:00 [entrez] AID - S0197-0186(07)00190-8 [pii] AID - 10.1016/j.neuint.2007.06.035 [doi] PST - ppublish SO - Neurochem Int. 2008 Jan;52(1-2):297-306. doi: 10.1016/j.neuint.2007.06.035. Epub 2007 Jul 4.