De Francesco Pablo Nicolás, Fernandez Gimena, Uriarte Maia, Urrutia Leandro, Ponce de León Magdalena, Fehrentz Jean-Alain, Falasco German, Perello Mario
Laboratory of Neurophysiology of the Multidisciplinary Institute of Cell Biology IMBICE, Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA), National University of La Plata, La Plata, Argentina.
Center of Molecular Imaging of Neurological Research Institute (FLENI), Escobar, Argentina.
Neuroendocrinology. 2023;113(1):64-79. doi: 10.1159/000526245. Epub 2022 Jul 29.
Ghrelin regulates a variety of functions by acting in the brain. The targets of ghrelin in the mouse brain have been mainly mapped using immunolabeling against c-Fos, a transcription factor used as a marker of cellular activation, but such analysis has several limitations. Here, we used positron emission tomography in mice to investigate the brain areas responsive to ghrelin.
We analyzed in male mice the brain areas responsive to systemically injected ghrelin using positron emission tomography imaging of 18F-fluoro-2-deoxyglucose (18F-FDG) uptake, an indicator of metabolic rate. Additionally, we studied if systemic administration of fluorescent ghrelin or native ghrelin displays symmetric accessibility or induction of c-Fos, respectively, in the brain of male mice.
Ghrelin increased 18F-FDG uptake in few specific areas of the isocortex, striatum, pallidum, thalamus, and midbrain at 0-10-min posttreatment. At the 10-20 and 20-30 min posttreatment, ghrelin induced mixed changes in 18F-FDG uptake in specific areas of the isocortex, striatum, pallidum, thalamus, and midbrain, as well as in areas of the olfactory areas, hippocampal and retrohippocampal regions, hypothalamus, pons, medulla, and even the cerebellum. Ghrelin-induced changes in 18F-FDG uptake were transient and asymmetric. Systemically administrated fluorescent-ghrelin-labeled midline brain areas known to contain fenestrated capillaries and the hypothalamic arcuate nucleus, where a symmetric labeling was observed. Ghrelin treatment also induced a symmetric increased c-Fos labeling in the arcuate nucleus.
DISCUSSION/CONCLUSION: Systemically injected ghrelin transiently and asymmetrically affects the metabolic activity of the brain of male mice in a wide range of areas, in a food intake-independent manner. The neurobiological bases of such asymmetry seem to be independent of the accessibility of ghrelin into the brain.
胃饥饿素通过作用于大脑来调节多种功能。在小鼠大脑中，胃饥饿素的作用靶点主要是通过针对c-Fos进行免疫标记来定位的，c-Fos是一种用作细胞活化标志物的转录因子，但这种分析存在一些局限性。在此，我们利用正电子发射断层扫描技术在小鼠中研究对胃饥饿素产生反应的脑区。
我们在雄性小鼠中，利用18F-氟-2-脱氧葡萄糖（18F-FDG）摄取的正电子发射断层扫描成像（代谢率的指标）分析对全身注射胃饥饿素产生反应的脑区。此外，我们研究了全身注射荧光胃饥饿素或天然胃饥饿素是否分别在雄性小鼠大脑中显示出对称的可及性或诱导c-Fos。
胃饥饿素在治疗后0至10分钟时增加了大脑皮质、纹状体、苍白球、丘脑和中脑的少数特定区域的18F-FDG摄取。在治疗后10至20分钟和20至30分钟时，胃饥饿素在大脑皮质、纹状体、苍白球、丘脑和中脑的特定区域以及嗅觉区域、海马和海马后区域、下丘脑、脑桥、延髓甚至小脑区域诱导了18F-FDG摄取的混合变化。胃饥饿素诱导的18F-FDG摄取变化是短暂且不对称的。全身注射荧光标记的胃饥饿素显示出已知含有有孔毛细血管的中线脑区和下丘脑弓状核有对称标记。胃饥饿素治疗还在弓状核中诱导了对称的c-Fos标记增加。
讨论/结论：全身注射胃饥饿素以食物摄入无关的方式在广泛区域中短暂且不对称地影响雄性小鼠大脑的代谢活性。这种不对称的神经生物学基础似乎与胃饥饿素进入大脑的可及性无关。
