Optogenetic stimulation of Kiss1(ARC) terminals in the AVPV induces surge-like luteinizing hormone secretion via glutamate release in mice.
Optogenetic stimulation of Kiss1(ARC) terminals in the AVPV induces surge-like luteinizing hormone secretion via glutamate release in mice.
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DOI：
10.3389/fendo.2022.1036235
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发表时间：
2022
影响因子：
5.2
通讯作者：
O'Byrne, Kevin T.
中科院分区：
文献类型：
--
作者：
Shen, Xi;Liu, Yali;Li, Xiao Feng;Long, Hui;Wang, Li;Lyu, Qifeng;Kuang, Yanping;O'Byrne, Kevin T.
Kisspeptin神经元主要位于弓状核（Kiss1ARC，相对于-à-vis GnRH脉冲发生器）和前腹侧脑室周围核（Kiss1AVPV，相对于-à-vis GnRH脉冲发生器）。Kiss1ARC发送与Kiss1AVPV体连接的纤维投射。然而，关于Kiss1ARC神经元在LH激增中的作用的研究有限，并且Kiss1ARC向AVPV的投射（Kiss1ARC→AVPV）在排卵前LH激增中的作用仍然未知。为了研究其功能，本研究采用光遗传学方法选择性刺激Kiss1ARC→AVPV，并测量循环LH水平的变化。通过病毒感染kiss - ccretdtomato小鼠的Kiss1ARC，使其表达通道视紫红质-2蛋白，并通过光纤套管选择性地在AVPV中施加光刺激。从15:30到16:30持续20 Hz的Kiss1ARC→AVPV光刺激可有效诱导LH在10分钟内立即增加，达到峰值8 ng/ml左右，随后在约40分钟内逐渐下降到基线水平。10赫兹的刺激导致LH水平无显著增加，而5赫兹的刺激对发情动物没有影响。与发情期和退情期相比，20 Hz刺激可显著提高发情前期的循环LH水平，提示末梢刺激的作用受性类固醇环境的调节。此外，AVPV内输注谷氨酸拮抗剂AP5+CNQX完全阻断Kiss1ARC→AVPV末端光刺激诱导的发情动物LH水平升高。这些结果首次证明，光刺激Kiss1ARC→AVPV通过谷氨酸能机制诱导LH激增样分泌。总之，Kiss1ARC可能通过AVPV末端突起的谷氨酸释放参与LH激增的产生。
Kisspeptin neurons are mainly located in the arcuate (Kiss1ARC, vis-à-vis the GnRH pulse generator) and anteroventral periventricular nucleus (Kiss1AVPV, vis-à-vis the GnRH surge generator). Kiss1ARC send fibre projections that connect with Kiss1AVPV somata. However, studies focused on the role of Kiss1ARC neurons in the LH surge are limited, and the role of Kiss1ARC projections to AVPV (Kiss1ARC→AVPV) in the preovulatory LH surge is still unknown. To investigate its function, this study used optogenetics to selectively stimulate Kiss1ARC→AVPV and measured changes in circulating LH levels. Kiss1ARC in Kiss-Cre-tdTomato mice were virally infected to express channelrhodopsin-2 proteins, and optical stimulation was applied selectively via a fibre optic cannula in the AVPV. Sustained 20 Hz optical stimulation of Kiss1ARC→AVPV from 15:30 to 16:30 h on proestrus effectively induced an immediate increase in LH reaching peak surge-like levels of around 8 ng/ml within 10 min, followed by a gradual decline to baseline over about 40 min. Stimulation at 10 Hz resulted in a non-significant increase in LH levels and 5 Hz stimulation had no effect in proestrous animals. The 20 Hz stimulation induced significantly higher circulating LH levels on proestrus compared with diestrus or estrus, which suggested that the effect of terminal stimulation is modulated by the sex steroid milieu. Additionally, intra-AVPV infusion of glutamate antagonists, AP5+CNQX, completely blocked the increase on LH levels induced by Kiss1ARC→AVPV terminal photostimulation in proestrous animals. These results demonstrate for the first time that optical stimulation of Kiss1ARC→AVPV induces an LH surge-like secretion via glutamatergic mechanisms. In conclusion, Kiss1ARC may participate in LH surge generation by glutamate release from terminal projections in the AVPV.
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影响因子：
4.1
作者：
Ping, L;Mahesh, VB;Brann, DW
通讯作者：
Brann, DW
影响因子：
3.4
作者：
Mahler, Stephen V.;Smith, Rachel J.;Aston-Jones, Gary
通讯作者：
Aston-Jones, Gary
DOI：
10.1073/pnas.1415226112
发表时间：
2014-12-23
影响因子：
11.1
作者：
Campos, Pauline;Herbison, Allan E.
通讯作者：
Herbison, Allan E.
影响因子：
4.8
作者：
Czieselsky, Katja;Prescott, Mel;Herbison, Allan E.
通讯作者：
Herbison, Allan E.
DOI：
10.3181/00379727-204-43651
发表时间：
1993-11-01
影响因子：
--
作者：
JOSHI, D;LEKHTMAN, I;MILLER, MM
通讯作者：
MILLER, MM