Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, United States.
Department of Psychiatry, Massachusetts General Hospital, Massachusetts, United States.
Elife. 2018 Jun 15;7:e35960. doi: 10.7554/eLife.35960.
Pituitary adenylate cyclase activating polypeptide (PACAP, ) is a neuromodulator implicated in anxiety, metabolism and reproductive behavior. PACAP global knockout mice have decreased fertility and PACAP modulates LH release. However, its source and role at the hypothalamic level remain unknown. We demonstrate that PACAP-expressing neurons of the ventral premamillary nucleus of the hypothalamus (PMV) project to, and make direct contact with, kisspeptin neurons in the arcuate and AVPV/PeN nuclei and a subset of these neurons respond to PACAP exposure. Targeted deletion of PACAP from the PMV through stereotaxic virally mediated cre- injection or genetic cross to LepR-i-cre mice with mice led to delayed puberty onset and impaired reproductive function in female, but not male, mice. We propose a new role for PACAP-expressing neurons in the PMV in the relay of nutritional state information to regulate GnRH release by modulating the activity of kisspeptin neurons, thereby regulating reproduction in female mice.
垂体腺苷酸环化酶激活肽（PACAP，）是一种神经调节剂，参与焦虑、代谢和生殖行为。PACAP 整体敲除小鼠的生育能力下降，PACAP 调节 LH 释放。然而，其在下丘脑水平的来源和作用仍不清楚。我们证明，下丘脑腹前乳核（PMV）中表达 PACAP 的神经元投射到并直接与弓状核和 AVPV/PeN 核中的 kisspeptin 神经元接触，其中一些神经元对 PACAP 暴露有反应。通过立体定向病毒介导的 cre 注射或遗传交叉将 PACAP 从 PMV 中靶向删除，与 LepR-i-cre 小鼠与 小鼠杂交，导致雌性而非雄性小鼠青春期起始延迟和生殖功能受损。我们提出了 PMV 中表达 PACAP 的神经元在将营养状态信息传递给调节 GnRH 释放中的新作用，通过调节 kisspeptin 神经元的活性来调节雌性小鼠的生殖。
