Juric Damijana Mojca, Miklic Spela, Carman-Krzan Marija
Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia.
Brain Res. 2006 Sep 7;1108(1):54-62. doi: 10.1016/j.brainres.2006.06.008. Epub 2006 Jul 7.
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.
星形胶质细胞作为三联突触的活跃组成部分,能够对突触释放的神经递质做出反应。由于脑源性神经营养因子(BDNF)除了由神经元产生外,也由星形胶质细胞产生,因此我们在本研究中重点关注单胺类物质去甲肾上腺素(NA)、5-羟色胺(5-HT)和多巴胺(DA)对来自特定脑区(皮层、小脑)的新生大鼠星形胶质细胞中BDNF蛋白合成的调节作用。所有测试的神经递质都能够有效且短暂地增加BDNF的细胞含量;它们的最大效应具有剂量和时间依赖性,并且在两个脑区之间存在差异。在培养的皮层星形胶质细胞中,NA(1微摩尔/升;6小时)使BDNF水平升高4倍,5-HT(1微摩尔/升;4小时)升高2.3倍,DA(150微摩尔/升;4小时)升高2.2倍。在小脑星形胶质细胞中,NA(1微摩尔/升;4小时)使BDNF含量增加4.7倍,5-HT(1微摩尔/升;4小时)增加1.7倍,DA(150微摩尔/升;4小时)增加1.4倍。当与单胺类物质的孵育时间延长超过12小时(对于5-HT)或24小时(对于NA和DA)时,BDNF水平的初始升高会恢复到基础水平。我们的结果证实了单胺能系统参与星形胶质细胞中BDNF产生的调节,并表明在神经元-星形胶质细胞相互作用中,单胺能神经元活动与星形胶质细胞神经营养支持之间存在正向相互作用,这在介导大脑中的神经元可塑性和营养功能方面具有动态作用。