Glutamate elicits release of BDNF from basal forebrain astrocytes in a process dependent on metabotropic receptors and the PLC pathway
Glutamate elicits release of BDNF from basal forebrain astrocytes in a process dependent on metabotropic receptors and the PLC pathway
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DOI：
10.1017/s1740925x09000052
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Dreyfus, Cheryl F.
中科院分区：
文献类型：
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作者：
Jean, Ying Y.;Lercher, Lauren D.;Dreyfus, Cheryl F.
负责基底前脑 (BF) 胆碱能神经元的存活和功能的关键神经营养因子是脑源性神经营养因子 (BDNF)。现在许多研究表明该因子的来源可能是 BF 星形胶质细胞。本研究旨在明确 BF 星形胶质细胞衍生的 BDNF 对胆碱能神经元的作用。此外，它还调查了调节 BDNF 含量和释放的监管事件。在最初的研究中，发现源自 BF 星形胶质细胞条件培养基 (ACM) 的 BDNF 可以增加 BF 乙酰胆碱酯酶 (AChE+) 胆碱能神经元和胆碱能合成酶胆碱乙酰转移酶 (ChAT) 的数量。蛋白质印迹、免疫细胞化学和药理学抑制研究表明，谷氨酸通过 I 类代谢型谷氨酸受体 (mGluR) 增加培养的 BF 星形胶质细胞中 BDNF 的细胞内水平及其释放。此外，BDNF 的释放是由 PLC、IP3 和内部 Ca2+ 储存的作用介导的。这些结果表明，BF 星形胶质细胞是胆碱能神经元 BDNF 的局部来源，并且它们可能通过 I 类代谢受体和 PLC 途径的介导，受到神经元信号谷氨酸的调节。
A key neurotrophin responsible for the survival and function of basal forebrain (BF) cholinergic neurons is brain-derived neurotrophic factor (BDNF). A number of studies now indicate that a source of this factor may be BF astrocytes. This study was designed to define the role of BF-astrocyte-derived BDNF on cholinergic neurons. Moreover, it investigated regulatory events that modulate BDNF content and release. In initial work BDNF derived from BF-astrocyte-conditioned medium (ACM) was found to increase both numbers of BF acetylcholinesterase (AChE+) cholinergic neurons and the cholinergic synthetic enzyme choline acetyltransferase (ChAT). Western blots, immunocytochemistry and pharmacological inhibition studies revealed that glutamate, through group I metabotropic glutamate receptors (mGluR), increases the intracellular levels of BDNF in BF astrocytes in culture, as well as its release. Furthermore, the release of BDNF is mediated by the actions of PLC, IP3 and internal stores of Ca2+. These results suggest that BF astrocytes serve as local sources of BDNF for cholinergic neurons, and that they may be regulated as such by the neuronal signal, glutamate, through the mediation of group I metabotropic receptors and the PLC pathway.