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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Prostaglandin E_2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation
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Prostaglandin E_2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation

机译：星形胶质细胞释放的前列腺素E_2通过EP2受体激活触发促性腺激素释放激素（GnRH）神经元放电

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摘要

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 fluo-roacetate (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-neu-ron 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.
机译：下丘脑中的星形胶质细胞响应神经元和神经胶质细胞引发的细胞信号转导释放前列腺素E_2（PGE_2）。释放后，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），后者是控制繁殖的神经肽。尚不清楚这种对GnRH分泌的影响是否伴随着这些神经元放电行为的改变。使用膜片钳记录，我们证明了PGE_2对GnRH神经元具有剂量依赖性的突触后兴奋作用。这些作用被EP2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（FA）对星形胶质细胞代谢的选择性抑制，可抑制脑切片中GnRH神经元的自发放电活性。同样，由于星形胶质细胞中有缺陷的erbB信号传导，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，下丘脑中的星形胶质细胞与神经元的通讯对于GnRH神经元的活动至关重要，并表明PGE_2在GnRH神经分泌系统中充当神经胶质递质。

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  • 作者

    Jerome Clasadonte; Pierre Poulain; Naresh K. Hanchate; Gabriel Corfas; Sergio R. Ojeda; Vincent Prevot;

  • 作者单位

    Institut National de la Sante et de la Recherche Medicale, Jean-Pierre Aubert Research Center, U837, Development and Plasticity of the Postnatal Brain, F-59000 Lille, France,Universite Lille Nord de France, Institut Federatif de Recherche 114, F-59000 Lille, France,UDSL, School of Medicine, F-59000 Lille, France;

    Institut National de la Sante et de la Recherche Medicale, Jean-Pierre Aubert Research Center, U837, Development and Plasticity of the Postnatal Brain, F-59000 Lille, France,Universite Lille Nord de France, Institut Federatif de Recherche 114, F-59000 Lille, France,UDSL, School of Medicine, F-59000 Lille, France;

    Institut National de la Sante et de la Recherche Medicale, Jean-Pierre Aubert Research Center, U837, Development and Plasticity of the Postnatal Brain, F-59000 Lille, France,Universite Lille Nord de France, Institut Federatif de Recherche 114, F-59000 Lille, France,UDSL, School of Medicine, F-59000 Lille, France;

    F. M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115,Departments of Neurology, Harvard Medical School, Boston, MA 02115,Departments of Otology and Laryngology, Harvard Medical School, Boston, MA 02115;

    Division of Neuroscierice, Oregon National Primate Research Center/Oregon Health and Science University, Beaverton, OR 97006;

    Institut National de la Sante et de la Recherche Medicale, Jean-Pierre Aubert Research Center, U837, Development and Plasticity of the Postnatal Brain, F-59000 Lille, France,Universite Lille Nord de France, Institut Federatif de Recherche 114, F-59000 Lille, France,UDSL, School of Medicine, F-59000 Lille, France;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cyclooxygenase; glia-to-neuron signaling; luteinizing hormone-releasing hormone; preoptic region; fertility;

    机译：环氧合酶胶质神经元信号;黄体生成素释放激素视前区生育能力;

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