Posterodorsal Medial Amygdala Urocortin-3, GABA, and Glutamate Mediate Suppression of LH Pulsatility in Female Mice.
Posterodorsal Medial Amygdala Urocortin-3, GABA, and Glutamate Mediate Suppression of LH Pulsatility in Female Mice.
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DOI：
10.1210/endocr/bqac196
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发表时间：
2022-12-19
期刊：
影响因子：
4.8
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中科院分区：
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杏仁内侧背侧亚核(MePD)是下丘脑-垂体-性腺(HPG)和下丘脑-垂体-肾上腺(HPA)轴的上游调节器。抑制MePD urocortin-3(Ucn3)神经元可阻止心理应激对雌性小鼠黄体生成素(LH)搏动性的抑制，同时阻断应激诱导的皮质酮(Cort)分泌的升高。我们探索了MePD Ucn3神经元抑制促性腺激素释放激素(GnRH)脉冲发生器的神经传递和神经回路，并进一步研究了MePD Ucn3向下丘脑室旁核(PVN)的传出投射是否控制皮质酮的分泌和黄体生成素的搏动性。Ucn3-cre-td番茄雌性卵巢切除(OVX)小鼠单侧注射腺相关病毒(AAV)-通道视紫红质2(ChR2)，并植入靶向MePD的光流管。我们用10赫兹的蓝光激活MePD中的Ucn3神经元，并监测其对促黄体生成素脉冲的影响。接下来，我们将光遗传刺激与GABAA或GABAB受体分别与荷包牡丹碱或CGP-35348的药理拮抗以及NMDA和AMPA受体拮抗剂AP5和CNQX分别联合使用，观察其对脉动性黄体生成素分泌的影响。另一组单独的Ucn3-cre-tdTomato Ovx小鼠用17个β-雌二醇替代，在MePD单侧注射AAVChR2，并植入针对下丘脑室旁核的光纤导管。我们用20 GHz的蓝光刺激PVN的MePD Ucn3传出投射，并监测其对皮质醇分泌和黄体生成素脉冲的影响。我们首次揭示，MePD内Ucn3神经元的激活通过GABA和谷氨酸信号抑制了GnRH脉冲发生频率，而MePD Ucn3投射到PVN调制了HPG和HPA轴。
The posterodorsal subnucleus of the medial amygdala (MePD) is an upstream modulator of the hypothalamic–pituitary–gonadal (HPG) and hypothalamic–pituitary–adrenal (HPA) axes. Inhibition of MePD urocortin-3 (Ucn3) neurons prevents psychological stress–induced suppression of luteinizing hormone (LH) pulsatility while blocking the stress-induced elevations in corticosterone (CORT) secretion in female mice. We explore the neurotransmission and neural circuitry suppressing the gonadotropin-releasing hormone (GnRH) pulse generator by MePD Ucn3 neurons and we further investigate whether MePD Ucn3 efferent projections to the hypothalamic paraventricular nucleus (PVN) control CORT secretion and LH pulsatility. Ucn3-cre-tdTomato female ovariectomized (OVX) mice were unilaterally injected with adeno-associated virus (AAV)-channelrhodopsin 2 (ChR2) and implanted with optofluid cannulae targeting the MePD. We optically activated Ucn3 neurons in the MePD with blue light at 10 Hz and monitored the effect on LH pulses. Next, we combined optogenetic stimulation of MePD Ucn3 neurons with pharmacological antagonism of GABAA or GABAB receptors with bicuculline or CGP-35348, respectively, as well as a combination of NMDA and AMPA receptor antagonists, AP5 and CNQX, respectively, and observed the effect on pulsatile LH secretion. A separate group of Ucn3-cre-tdTomato OVX mice with 17β-estradiol replacement were unilaterally injected with AAV-ChR2 in the MePD and implanted with fiber-optic cannulae targeting the PVN. We optically stimulated the MePD Ucn3 efferent projections in the PVN with blue light at 20 Hz and monitored the effect on CORT secretion and LH pulses. We reveal for the first time that activation of Ucn3 neurons in the MePD inhibits GnRH pulse generator frequency via GABA and glutamate signaling within the MePD, while MePD Ucn3 projections to the PVN modulate the HPG and HPA axes.
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影响因子：
3.1
作者：
Comninos AN;Anastasovska J;Sahuri-Arisoylu M;Li X;Li S;Hu M;Jayasena CN;Ghatei MA;Bloom SR;Matthews PM;O'Byrne KT;Bell JD;Dhillo WS
通讯作者：
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影响因子：
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Adekunbi DA;Li XF;Li S;Adegoke OA;Iranloye BO;Morakinyo AO;Lightman SL;Taylor PD;Poston L;O'Byrne KT
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O'Byrne KT
影响因子：
5.3
作者：
Deussing, Jan M.;Breu, Johannes;Wurst, Wolfgang
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Wurst, Wolfgang
影响因子：
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作者：
Cavalcante, Judney Cley;Sita, Luciane Valeria;Elias, Carol Fuzeti
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Elias, Carol Fuzeti
DOI：
10.1073/pnas.1003969107
发表时间：
2010-05-04
影响因子：
11.1
作者：
Kuperman, Yael;Issler, Orna;Chen, Alon
通讯作者：
Chen, Alon