Prostaglandin E2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation
Prostaglandin E2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation
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DOI：
10.1073/pnas.1107533108
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发表时间：
2011-09-20
影响因子：
11.1
通讯作者：
Prevot, Vincent
中科院分区：
文献类型：
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作者：
Clasadonte, Jerome;Poulain, Pierre;Prevot, Vincent
下丘脑中的星形胶质细胞释放前列腺素E-2（PGE（2）），以响应神经元和神经胶质细胞启动的细胞间信号传导。一旦释放，PGE（2）刺激下丘脑神经内分泌神经元分泌促性腺激素释放激素（GnRH），这是一种控制生殖的神经肽。这种对GnRH分泌的影响是否伴随着这些神经元放电行为的变化尚不清楚。用膜片钳技术证明PGE（2）对GnRH神经元有剂量依赖性的突触后兴奋作用。这些作用被EP 2受体激动剂模拟，并被蛋白激酶A（PKA）抑制剂减弱。吲哚美辛（INDO）对前列腺素合成的急性阻断或氟乙酸盐（FA）对星形胶质细胞代谢的选择性抑制可抑制脑片中GnRH神经元的自发放电活动。同样，由于星形胶质细胞中erbB信号缺陷，星形胶质细胞PGE（2）释放受损的小鼠GnRH神经元活性降低。这些结果表明，下丘脑星形胶质细胞与神经元之间的通讯对于GnRH神经元的活动是必不可少的，并表明PGE（2）在GnRH神经分泌系统中起胶质递质的作用。
Astrocytes in the hypothalamus release prostaglandin E-2 (PGE(2)) in response to cell-cell signaling initiated by neurons and glial cells. Upon release, PGE(2) stimulates the secretion of gonadotropin-releasing hormone (GnRH), the neuropeptide that controls reproduction, from hypothalamic neuroendocrine neurons. Whether this effect on GnRH secretion is accompanied by changes in the firing behavior of these neurons is unknown. Using patch-clamp recording we demonstrate that PGE(2) exerts a dose-dependent postsynaptic excitatory effect on GnRH neurons. These effects are mimicked by an EP2 receptor agonist and attenuated by protein kinase A (PKA) inhibitors. The acute blockade of prostaglandin synthesis by indomethacin (INDO) or the selective inhibition of astrocyte metabolism by fluoroacetate (FA) suppresses the spontaneous firing activity of GnRH neurons in brain slices. Similarly, GnRH neuronal activity is reduced in mice with impaired astrocytic PGE(2) release due to defective erbB signaling in astrocytes. These results indicate that astrocyte-to-neuron communication in the hypothalamus is essential for the activity of GnRH neurons and suggest that PGE(2) acts as a gliotransmitter within the GnRH neurosecretory system.