Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK.
J Neuroendocrinol. 2023 Aug;35(8):e13315. doi: 10.1111/jne.13315. Epub 2023 Jun 27.
The dorsal vagal complex (DVC) regulates diverse aspects of physiology including food intake and blood glucose homeostasis. Astrocytes play an active role in regulating DVC function and, by extension, physiological parameters. DVC astrocytes in ex vivo slices respond to low tissue glucose. The response of neurons to low glucose is conditional on intact astrocyte signalling in slice preparations, suggesting astrocytes are primary sensors of glucose deprivation (glucoprivation). Based on these published findings we hypothesised that in vivo DVC astrocyte manipulation with chemogenetics would be sufficient to alter physiological responses that control blood glucose. We found that 2-h after systemic 2-DG-induced glucoprivation there were no observable changes in morphology of glial fibrillary acidic protein (GFAP)-immunoreactive DVC cells, specifically those in the nucleus of the solitary tract (NTS). Chemogenetic activation of DVC astrocytes was sufficient to suppress nocturnal food intake by reducing both meal size and meal number and this manipulation also suppressed 2-DG-induced glucoprivic food intake. Chemogenetic activation of DVC astrocytes did not increase basal blood glucose nor protect against insulin-induced hypoglycaemia. In male mice, chemogenetic DVC astrocyte activation did not alter glucose tolerance. In female mice, the initial glucose excursion was reduced in a glucose tolerance test, suggesting enhanced glucose absorption. Based on our data and published work, we propose that DVC astrocytes may play an indispensable homeostatic role, that is, are necessary to maintain the function of glucoregulatory neuronal circuitry, but alone their bulk activation is not sufficient to result in adaptive glucoregulatory responses. It is possible that there are state-dependent effects and/or DVC astrocyte subsets that have this specialised role, but this was unresolvable using the experimental approaches employed here.
背侧迷走复合体（DVC）调节多种生理过程，包括食物摄入和血糖稳态。星形胶质细胞在调节 DVC 功能方面发挥着积极的作用，从而影响生理参数。在离体切片中，DVC 星形胶质细胞对低组织葡萄糖有反应。神经元对低血糖的反应取决于切片制备中星形胶质细胞信号的完整性，这表明星形胶质细胞是葡萄糖剥夺（糖剥夺）的主要传感器。基于这些已发表的发现，我们假设通过化学遗传学对体内 DVC 星形胶质细胞进行操作足以改变控制血糖的生理反应。我们发现，在全身 2-DG 诱导糖剥夺后 2 小时，神经胶质纤维酸性蛋白（GFAP）免疫反应性 DVC 细胞的形态没有观察到变化，特别是在孤束核（NTS）中。DVC 星形胶质细胞的化学遗传激活足以通过减少餐量和餐数来抑制夜间摄食，这种操作也抑制了 2-DG 诱导的糖剥夺性摄食。DVC 星形胶质细胞的化学遗传激活不会增加基础血糖，也不能防止胰岛素引起的低血糖。在雄性小鼠中，化学遗传激活 DVC 星形胶质细胞不会改变葡萄糖耐量。在雌性小鼠中，葡萄糖耐量试验中的初始葡萄糖波动减小，表明葡萄糖吸收增强。基于我们的数据和已发表的工作，我们提出 DVC 星形胶质细胞可能发挥不可或缺的稳态作用，即维持葡萄糖调节神经元回路的功能是必要的，但它们的大量激活本身不足以导致适应性的葡萄糖调节反应。可能存在状态依赖的效应和/或具有这种特殊作用的 DVC 星形胶质细胞亚群，但使用这里采用的实验方法无法解决这个问题。
