Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, United States.
Department of OBGYN and Reproductive Sciences, University of California, San Diego, La Jolla, CA, United States.
Front Endocrinol (Lausanne). 2023 Feb 10;14:1093592. doi: 10.3389/fendo.2023.1093592. eCollection 2023.
Reproduction is regulated through the hypothalamic-pituitary-gonadal (HPG) axis, largely the action of kisspeptin neurons in the hypothalamus. Importantly, neurons have been identified in other brain regions, including the medial amygdala (MeA). Though the MeA is implicated in regulating aspects of both reproductive physiology and behavior, as well as non-reproductive processes, the functional roles of MeA neurons are largely unknown. Additionally, besides their stimulation by estrogen, little is known about how MeA neurons are regulated. Using a RiboTag mouse model in conjunction with RNA-seq, we examined the molecular profile of MeA neurons to identify transcripts that are co-expressed in MeA neurons of female mice and whether these transcripts are modulated by estradiol (E) treatment. RNA-seq identified >13,800 gene transcripts co-expressed in female MeA neurons, including genes for neuropeptides and receptors implicated in reproduction, metabolism, and other neuroendocrine functions. Of the >13,800 genes co-expressed in MeA neurons, only 45 genes demonstrated significantly different expression levels due to E treatment. Gene transcripts such as , , and increased in response to E treatment, while fewer transcripts, such as and , were downregulated by E. Dual RNAscope and immunohistochemistry was performed to validate co-expression of MeA with and . These results are the first to establish a profile of genes actively expressed by MeA neurons, including a subset of genes regulated by E, which provides a useful foundation for future investigations into the regulation and function of MeA neurons.
生殖是通过下丘脑-垂体-性腺（HPG）轴调节的，主要是下丘脑 kisspeptin 神经元的作用。重要的是，已经在其他脑区鉴定到神经元，包括内侧杏仁核（MeA）。尽管 MeA 被认为参与调节生殖生理学和行为的各个方面，以及非生殖过程，但 MeA 神经元的功能作用在很大程度上尚不清楚。此外，除了雌激素刺激外，人们对 MeA 神经元如何被调节知之甚少。我们使用 RiboTag 小鼠模型结合 RNA-seq，检查了 MeA 神经元的分子特征，以鉴定在雌性小鼠的 MeA 神经元中共表达的转录本，以及这些转录本是否受雌二醇（E）处理的调节。RNA-seq 鉴定出 >13800 个在雌性 MeA 神经元中共表达的基因转录本，包括与生殖、代谢和其他神经内分泌功能相关的神经肽和受体的基因。在 >13800 个在 MeA 神经元中共表达的基因中，只有 45 个基因由于 E 处理而表现出显著不同的表达水平。基因转录本，如 、 、和 ，对 E 处理有反应而增加，而较少的转录本，如 、和 ，则被 E 下调。进行了双重 RNAscope 和免疫组织化学，以验证 MeA 与 和 的共表达。这些结果首次建立了 MeA 神经元主动表达的基因图谱，包括受 E 调节的基因亚群，为未来研究 MeA 神经元的调节和功能提供了有用的基础。
