A role for glial fibrillary acidic protein (GFAP)-expressing cells in the regulation of gonadotropin-releasing hormone (GnRH) but not arcuate kisspeptin neuron output in male mice.
A role for glial fibrillary acidic protein (GFAP)-expressing cells in the regulation of gonadotropin-releasing hormone (GnRH) but not arcuate kisspeptin neuron output in male mice.
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DOI：
10.7554/elife.68205
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发表时间：
2021-07-22
期刊：
影响因子：
7.7
通讯作者：
Moenter SM
中科院分区：
文献类型：
--
作者：
Vanacker C;Defazio RA;Sykes CM;Moenter SM
GnRH神经元是调节生育能力的最终中枢神经输出。下丘脑弓状核中的Kisspeptin神经元（KNDy神经元）被认为是GnRH输出的主要调节器。GnRH和KNDy神经元被星形胶质细胞包围，星形胶质细胞可以调节神经元活动并进行远距离通信。前列腺素E2（PGE 2）主要由星形胶质细胞合成，增加GnRH神经元活性和下游垂体释放促黄体激素（LH）。我们假设胶质细胞酸性蛋白（GFAP）表达星形胶质细胞在调节GnRH和/或KNDy神经元活性和LH释放中发挥作用。我们使用腺相关病毒将设计者受体（DREADD）靶向设计者药物专门激活的GFAP表达细胞，以激活Gq或Gi介导的信号传导。在视前区激活Gq信号，靠近GnRH神经元，但不在弓状核，通过部分依赖于PGE 2的机制增加体内LH释放和体外GnRH放电。这些数据表明，星形胶质细胞可以激活GnRH/LH释放的方式独立于KNDy神经元。
GnRH neurons are the final central neural output regulating fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (KNDy neurons) are considered the main regulator of GnRH output. GnRH and KNDy neurons are surrounded by astrocytes, which can modulate neuronal activity and communicate over distances. Prostaglandin E2 (PGE2), synthesized primarily by astrocytes, increases GnRH neuron activity and downstream pituitary release of luteinizing hormone (LH). We hypothesized that glial fibrillary acidic protein (GFAP)-expressing astrocytes play a role in regulating GnRH and/or KNDy neuron activity and LH release. We used adeno-associated viruses to target designer receptors exclusively activated by designer drugs (DREADDs) to GFAP-expressing cells to activate Gq- or Gi-mediated signaling. Activating Gq signaling in the preoptic area, near GnRH neurons, but not in the arcuate, increases LH release in vivo and GnRH firing in vitro via a mechanism in part dependent upon PGE2. These data suggest that astrocytes can activate GnRH/LH release in a manner independent of KNDy neurons.