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Noradrenergic stimulation of BDNF synthesis in astrocytes: Mediation via α1- and β1/β2-adrenergic receptors
- Source :
- Neurochemistry International. 52:297-306
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- 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.
- Subjects :
- Agonist
medicine.medical_specialty
Adrenergic receptor
medicine.drug_class
Adrenergic
Enzyme-Linked Immunosorbent Assay
Stimulation
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Adrenergic Agents
Pregnancy
Internal medicine
Prazosin
medicine
Animals
Rats, Wistar
Cells, Cultured
Brain-derived neurotrophic factor
Forskolin
Chemistry
Brain-Derived Neurotrophic Factor
Cell Biology
Rats
Receptors, Adrenergic
Endocrinology
medicine.anatomical_structure
Astrocytes
Neuroglia
Female
medicine.drug
Subjects
Details
- ISSN :
- 01970186
- Volume :
- 52
- Database :
- OpenAIRE
- Journal :
- Neurochemistry International
- Accession number :
- edsair.doi.dedup.....480890515847c393b7a23fa97c44ee7e