Yacawych Warren T, Palmer Alexandra L, Doczi Megan A
Department of Biology, Norwich University, 158 Harmon Drive, Northfield, VT, 05663, USA.
Department of Biology, Norwich University, 158 Harmon Drive, Northfield, VT, 05663, USA.
Neurosci Lett. 2019 Apr 17;698:126-132. doi: 10.1016/j.neulet.2019.01.009. Epub 2019 Jan 4.
The hypothalamus is a brain region critical for the homeostatic regulation of appetite and energy expenditure. Hypothalamic neuronal activity that is altered during development can produce permanent physiological changes later in life. For example, circulating hormones such as insulin have been shown to influence hypothalamic neuronal projections, leading to altered metabolism in adult rodents. While insulin signaling in the post-hatch chicken has been shown to mirror that of mammals, the developmental role of insulin in the avian embryonic hypothalamus remains largely unexplored. Here we present the earliest known evidence for insulin receptor (InsR) expression in embryonic avian hypothalamic nuclei governing energy homeostasis. RT-PCR analysis reveals InsR mRNA in E8, E10, and E12 neurons while western blot data demonstrate protein expression in E12 avian whole brain and hypothalamic lysates. Immunohistochemical analysis of avian hypothalamic brain slices demonstrates a shift in InsR localization from paraventricular expression in E8 to a more defined concentration of InsR in developmental regions resembling the ventromedial hypothalamus (VMH) and arcuate nucleus (ARC) in E12 time points. In addition, InsR expression appears in a heterogeneous pattern, suggesting receptor localization to subpopulations of avian hypothalamic neurons as early as E8. With increasing evidence suggesting energy homeostasis pathways may be altered via the gestational environment, it is important to understand how insulin signaling may affect embryogenesis. Our research provides evidence for the earliest known embryonic expression of InsR protein in the avian hypothalamus and may suggest a developmental role for insulin signaling in the early patterning of metabolic pathways in the central nervous system.
下丘脑是一个对食欲和能量消耗的稳态调节至关重要的脑区。发育过程中发生改变的下丘脑神经元活动可在生命后期产生永久性的生理变化。例如，胰岛素等循环激素已被证明会影响下丘脑神经元投射，导致成年啮齿动物的新陈代谢发生改变。虽然孵化后鸡体内的胰岛素信号传导已被证明与哺乳动物相似，但胰岛素在禽类胚胎下丘脑发育中的作用在很大程度上仍未被探索。在此，我们展示了胰岛素受体（InsR）在调控能量稳态的禽类胚胎下丘脑核中表达的最早已知证据。逆转录聚合酶链反应（RT-PCR）分析显示E8、E10和E12神经元中有InsR信使核糖核酸（mRNA），而蛋白质印迹数据表明E12禽类全脑和下丘脑裂解物中有蛋白质表达。对禽类下丘脑脑片的免疫组织化学分析表明，InsR定位从E8时的室旁表达转变为E12时间点在类似于腹内侧下丘脑（VMH）和弓状核（ARC）的发育区域中更明确的InsR浓度。此外，InsR表达呈现出异质性模式，表明早在E8时受体就定位于禽类下丘脑神经元亚群。随着越来越多的证据表明能量稳态途径可能会因妊娠环境而改变，了解胰岛素信号传导如何影响胚胎发生很重要。我们的研究为InsR蛋白在禽类下丘脑中最早已知的胚胎表达提供了证据，并可能暗示胰岛素信号传导在中枢神经系统代谢途径早期模式形成中的发育作用。
