Monoaminergic neuronal activity up-regulates BDNF synthesis in cultured neonatal rat astrocytes.
Astrocytes as an active part of the tripartite synapse can respond to the synaptically released neurotransmitters. Because brain-derived neurotrophic factor (BDNF) is produced by astrocytes, in addition to neurons, we focused our present study on the regulatory effects of monoamines noradrenaline (NA), serotonin (5-HT), and dopamine (DA) on the synthesis of BDNF protein in rat neonatal astrocytes from specific brain regions (cortex, cerebellum). All tested neurotransmitters are able to potently and transiently increase BDNF cellular contents; their maximal effects are dose and time dependent and differ between the two brain regions. In cultured cortical astrocytes, NA (1 microM; 6 h) elevates BDNF levels by a 4-fold, 5-HT (1 microM; 4 h) by a 2.3-fold, and DA (150 microM; 4 h) by a 2.2-fold. In cerebellar astrocytes, NA (1 microM; 4 h) increases BDNF content by a 4.7-fold, 5-HT (1 microM; 4 h) by a 1.7-fold, and DA (150 microM; 4 h) by a 1.4-fold. The initial increase in the BDNF levels return to basal levels when incubation with monoamines is extended beyond 12 h (for 5-HT) or 24 h (for NA and DA). Our results confirm the involvement of monoaminergic systems in the regulation of BDNF production in astrocytes and suggest the existence of a positive reciprocal interaction between monoaminergic neuronal activity and astrocytic neurotrophic support in neuron-astrocyte crosstalk, which has a dynamic role in mediating neuronal plasticity and trophic functions in the brain.
Juric
Damijana Mojca
DM
Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia. damijana-mojca.juric@mf.uni-lj.si
Miklic
Spela
S
Carman-Krzan
Marija
M
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015306:Biogenic Monoamines / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D015306:Biogenic Monoamines; D019208:Brain-Derived Neurotrophic Factor; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine