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 mu M; 6h) elevates BDNF levels by a 4-fold, 5-HT (1 mu M; 4h) by a 2.3-fold, and DA (150 mu M; 4h) by a 2.2-fold. In cerebellar astrocytes, NA (1 mu M; 4h) increases BDNF content by a 4.7-fold, 5-HT (1 mu M; 4h) by a 1.7-fold, and DA (150 mu M; 4h) by a 1.4-fold. The initial increase in the BDNF levels return to basal levels when incubation with monoamines is extended beyond 12h (for 5-HT) or 24h (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. (c) 2006 Elsevier B.V. All rights reserved.